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Semaglutide Continues to Impress: Phase 3 Trial Shows Reversal of MASH (Metabolic Dysfunction-Associated Steatohepatitis)

by with No Comment Clinical Trails

Medically Reviewed By Vikas Londhe, M.Pharm, Pharmacology

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Source: Freepik.Com

A new large phase 3 clinical study has shown encouraging results for a medicine called semaglutide in treating people with a serious liver disease known as MASH (metabolic dysfunction-associated steatohepatitis). MASH is a more severe form of fatty liver disease that can lead to serious health problems like liver scarring (cirrhosis) and even liver cancer if not treated. Semaglutide is a drug that works by mimicking a natural hormone in the body called GLP-1 that helps control blood sugar and appetite. These new findings, which were published in a medical journal The New England Journal of Medicine, represent an important breakthrough, especially since there are currently very few effective treatments available for this condition.

Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Metabolic Dysfunction-Associated Steatohepatitis, or MASH, is a serious liver disease that happens in people who have health problems like obesity, type 2 diabetes, or high cholesterol. It used to be called non-alcoholic steatohepatitis (NASH), but the name was changed to highlight its link to metabolic health issues.

In MASH, fat builds up in the liver, which causes swelling and damage to liver cells. Over time, this can lead to scarring of the liver (called fibrosis), and if it gets worse, it can turn into cirrhosis, which is severe and lasting liver damage. In the most serious cases, it can even lead to liver failure or liver cancer.

MASH is becoming more common all over the world because more people are living with obesity and diabetes. It usually doesn’t cause any symptoms at first, so many people don’t know they have it until their liver is already damaged.

As of now, resmetirom is the only FDA-approved treatment specifically for MASH with liver fibrosis. Hence, there is an emerging need for alternate options for treating MASH.

Key findings from the ESSENCE Trial

The ESSENCE trial was a major research study that included 1,197 people who had MASH (a serious liver condition) confirmed through a liver biopsy. These patients also had moderate to severe liver scarring (stage 2 or 3 fibrosis). The study was designed as a “double-blind, placebo-controlled” trial. Participants were randomly divided so that for every two people receiving semaglutide, one person received a placebo. They were given either 2.4 mg of semaglutide or the placebo once a week for a total planned duration of 240 weeks (over 4.5 years). The current findings are from an early look at the data after 72 weeks (about 1.5 years) of treatment, involving the first 800 people in the study.

How Well Semaglutide Worked in the Study

Semaglutide showed strong benefits for people with MASH across several key health measures:

Liver inflammation reduced without getting worsening of scar:

About 63% of patients who took semaglutide had declined their liver inflammation (steatohepatitis) without worsening to fibrosis. In comparison, only about 34% of those who took the placebo saw the same result. That’s a nearly 29% better outcome with semaglutide, and the result was statistically significant.

Improved liver scarring without more inflammation:

Nearly 37% of patients taking semaglutide had improvement in liver fibrosis without their liver inflammation worsening. For the placebo group, only 22% saw this kind of improvement a difference of over 14% is also statistically significant.

Both inflammation and scarring improved:

Around 33% of those on semaglutide saw improvements in both liver inflammation and scarring, which was more than double the 16% who experienced the same benefits in the placebo group.

These findings suggest semaglutide could become a highly effective treatment for people with MASH, addressing both inflammation and damage in the liver.

Beyond the improvements seen in liver tissue, semaglutide also helped patients in other important ways. People who took semaglutide lost a significant amount of weight, on average; they lost about 10.5% of their body weight, compared to just 2% in the placebo group. This is a major benefit, especially since excess weight is a key factor in MASH.

Semaglutide also improved several markers related to overall metabolism and health. It helped reduce insulin resistance, lowered levels of triglycerides and cholesterol, and decreased markers of inflammation. These improvements are important because they not only support liver health but also reduce the risk of heart disease and diabetes, which are common in people with MASH.

Safety and Side Effects

Semaglutide was generally safe and well tolerated by patients in the study. The side effects reported were mostly in line with what has been seen in earlier research. The most common issues were stomach-related problems like nausea and diarrhea, which happened more often in people taking semaglutide compared to those on the placebo.

However, serious side effects occurred at about the same rate in both groups, around 13.4% showing that semaglutide did lead to more serious health problems overall. Importantly, no new safety issues were found during the trial, including any liver-related complications, which is reassuring for people with liver disease.

Clinical Implications

The findings from this study show that semaglutide has the potential to not only reduce liver inflammation and scarring in people with MASH, but also improve overall metabolic health. This is especially important because MASH is often linked to other serious conditions like type 2 diabetes and obesity. Since semaglutide helps with both liver disease and these related metabolic issues, it could become a powerful option integrated treatment strategy.

Currently, another drug called resmetirom has received fast-track approval from the FDA for treating MASH with fibrosis. However, based on semaglutide performance in this early analysis, it may soon be approved as well and possibly offer even broader benefits than existing treatments.

What’s Next: Long-Term Outlook

The ESSENCE trial is still in progress, and researchers will continue to follow patients for a total of 240 weeks (about 4.5 years) to understand the long-term effects of semaglutide. One of the key outcomes they’re watching for is whether the drug can help patients avoid serious complications like cirrhosis over time.

If the final results confirm the benefits seen so far such as improved liver health, weight loss, and better metabolic control semaglutide could become a game-changing treatment for MASH. This would be especially important for a disease that has had very few effective options until now.

References

1.Arun J. Sanyal, Philip N. Newsome, Iris Kliers et al, Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis, April 30, 2025, at NEJM, DOI: 10.1056/NEJMoa2413258

2. Metabolic Dysfunction-Associated Steatohepatitis (MASH), Cleveland Clinic, available from https://my.clevelandclinic.org/health/diseases/22988-nonalcoholic-steatohepatitis

3. Keam SJ. Resmetirom: First Approval. Drugs. 2024 Jun; 84(6):729-735. Doi: 10.1007/s40265-024-02045-0. Epub 2024 May 21. PMID: 38771485.

4. Bandyopadhyay S, Das S, Samajdar SS, Joshi SR. Role of semaglutide in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Metab Syndr. 2023 Oct;17(10):102849. Doi: 10.1016/j.dsx.2023.102849. Epub 2023 Sep 13. PMID: 37717295.

5. Zhu K, Kakkar R, Chahal D, Yoshida EM, Hussaini T. Efficacy and safety of semaglutide in non-alcoholic fatty liver disease. World J Gastroenterology. 2023 Oct 7;29(37):5327-5338. Doi: 10.3748/wjg.v29.i37.5327. PMID: 37899788; PMCID: PMC10600803.

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Is Cytisinicline the Next Big Thing in Quitting Smoking?

by with No Comment Clinical Trails

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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Source: Freepik.Com

Smoking is the leading cause of preventable death worldwide. Smoke from cigarette contains mixture of toxic chemicals, nearly 5000 chemicals produced during combustion of tobacco and its additives and many of these have harmful effect on every organ of the body. Out of these 5000 chemicals 70 chemicals are the known carcinogens like, formaldehyde, vinyl chloride etc.

But if these chemicals are all harmful and can leads to serious health condition like cancer then why people find it difficult to quit smoking? Nicotine is the chemical present in cigarette, which is highly addictive but it is non carcinogen. Nicotine makes people habitual to smoking.

Health effects of smoking

Smoking is the leading cause of many life-threatening health conditions. Smoking is the main contributor to lung cancer worldwide. Apart from this, smoking is the leading cause of heart disease, stroke, chronic obstructive pulmonary disease (COPD), and many other life-threatening conditions. Smoking can significantly increase the risk of other ailments, including type 2 diabetes, infertility, and pregnancy complications. As this is the established link in active smokers, smoking can cause serious health problems in passive non-smokers, or secondhand smokers who are exposed to smoke from primary smokers, especially children. Passive smoking can lead to health conditions like asthma, respiratory infections, or sudden infant death syndrome (SIDS). The other effects of smoking can include an economic burden on patients from healthcare costs and, at the same time, productivity loss at the workplace.

Prevalence worldwide

According to WHO report 2023, there are 1.1 billion active smokers present worldwide—smoking causes more than 8 million deaths per year globally. As per the CDC report 2023, in the USA alone, 11.5% of adults smoke; out of these, 480,000 deaths occur due to smoking annually in the USA. 41000 deaths are associated with passive smoking annually due to smoking. It all increases the economic burden up to 300 billion dollar.

Conventional smoking therapies

Conventional smoking therapies include Nicotine Replacement Therapy (NRT). It is one of the most commonly used methods and comes in several forms, like patches, gums, lozenges, inhalers, and nasal sprays. Prescription medications such as varenicline, a partial agonist at nicotinic receptors, and bupropion, an antidepressant that helps reduce cravings and withdrawal symptoms, are also widely used. Other behavioral therapies are also included in treatment regimens.

However, even if this therapies are beneficial, these therapies come with drawbacks: NRT may not fully cure psychological dependency on smoking, bupropion and varenicline can cause side effects like insomnia, mood changes, and nausea, and behavioural therapy often requires long-term commitment, access to trained professionals, and consistent follow-up, which can be barriers for many smoking quitters.

What is Cytisinicline?

Cytisinicline is a plant-based alkaloid derived from Cytisus laburnum (golden rain tree). It has been used for decades in Eastern Europe as a smoking cessation aid, particularly in Bulgaria and Poland, under the brand name Tabex. Structurally and pharmacologically, it shares similarities with varenicline, a well-known partial agonist of the nicotinic acetylcholine receptor (nAChR).

Unlike nicotine, which fully activates neuronal nicotinic acetylcholine receptors, cytisinicline acts as a partial agonist, stimulating the receptor enough to reduce withdrawal symptoms and cravings while also blocking nicotine’s ability to bind and create the rewarding “high.” This dual action is what makes cytisinicline so promising.

How Does Cytisinicline Work?

Cytisinicline targets the α4β2 subtype of nicotinic acetylcholine receptors in the brain. These receptors play a key role in the addictive properties of nicotine. By binding to them, cytisinicline helps:

Reduce nicotine withdrawal symptoms

Diminish the rewarding effects of smoking

Ease the transition away from tobacco products

Its mechanism is very similar to that of varenicline, but cytisinicline may have a better safety and tolerability profile, which is a major advantage.

Clinical Evidence and Recent Trials

While cytisinicline has a long history of use in Eastern Europe, it has only recently undergone rigorous clinical trials in the U.S. and other Western countries.

ORCA-1 Trial (2020): This Phase 2b trial showed that cytisinicline significantly improved quit rates compared to placebo. Importantly, the drug was well-tolerated, with fewer reported side effects than varenicline.

ORCA-2 Trial (2022): A pivotal Phase 3 study that met its primary endpoint. The trial demonstrated that a 12-week course of cytisinicline significantly increased smoking abstinence compared to placebo. The quit rates were approximately 2.6 to 6.3 times higher than placebo, depending on the dosing regimen.

ORCA-3 Trial (2024): The most recent Phase 3 trial confirmed the results of ORCA-2, showing sustained abstinence at 6 and 12 weeks, with very few adverse events. The most common side effects were mild gastrointestinal discomfort and sleep disturbances.

Safety Profile

Across multiple studies, cytisinicline has been well tolerated. The most frequently reported side effects Nausea, Abnormal dreams, Insomnia, Headache, Fatigue and Anxiety. Cytisinicline appears to have a more favourable side effect profile compared to varenicline. Cytisinicline is associated with lower rates of nausea and sleep disturbances.

Conclusion

Cytisinicline is emerging as a serious contender in the smoking cessation space. With a strong safety profile, promising efficacy, and a natural origin, it could offer a much-needed alternative to current therapies. If FDA approved, cytisinicline may become a first-line option for smokers trying to quit and possibly the next big thing in the fight against nicotine addiction.

References

1.Varghese J, Muntode Gharde P. A Comprehensive Review on the Impacts of Smoking on the Health of an Individual. Cureus. 2023 Oct 5;15(10):e46532. doi: 10.7759/cureus.46532. PMID: 37927763; PMCID: PMC10625450.

2. Edward D. Gometz, Health Effects of Smoking and the Benefits of Quitting, AMA journal of ethics, Jan 2011, available from https://journalofethics.ama-assn.org/article/health-effects-smoking-and-benefits-quitting/2011-01

3. WHO report on the global tobacco epidemic, 2023: protect people from tobacco smoke, 31 July 2023, World Health Organization, available from https://www.who.int/publications/i/item/9789240077164

4. Notes from the Field: Tobacco Product Use Among Adults — United States, 2017–2023, Morbidity and Mortality Weekly Report, March 6, 2025 / 74(7);118–121

5. Nides M, Rigotti NA, Benowitz N, Clarke A, Jacobs C. A Multicenter, Double-Blind, Randomized, Placebo-Controlled Phase 2b Trial of Cytisinicline in Adult Smokers (The ORCA-1 Trial). Nicotine Tob Res. 2021 Aug 29;23(10):1656-1663. doi: 10.1093/ntr/ntab073. PMID: 33847362; PMCID: PMC8403245.

6. Rigotti NA, Benowitz NL, Prochaska J, et al. Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. JAMA.2023; 330(2):152–160. doi:10.1001/jama.2023.10042

7. Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA Intern Med.Published online April 21, 2025. doi:10.1001/jamainternmed.2025.0628

8. Current Cigarette Smoking among Adults in the United States, 17 Sep 2024, Smoking and Tobacco Use available from https://www.cdc.gov/tobacco/php/data-statistics/adult-data-cigarettes/index.html

9. Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010. 3, Chemistry and Toxicology of Cigarette Smoke and Biomarkers of Exposure and Harm. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53014/

10. What’s in a cigarette? Cancer research UK, available from https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/smoking-and-cancer/whats-in-a-cigarette-0

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Top 5 Daily Habits That Can Help You Beat Anxiety for Good

by with No Comment Lifestyle

Medically Reviewed by Dr. Abhijeet Ghangale Neurosurgeon (MBBS, MCh-Neurosurgery)

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Source: Freepik.Com

You must be nervous before that important interview or fearful when crossing that difficult patch during the trek. Still, in most cases, you must have also noticed that due to that nervousness, you gave that interview well, or due to your fearful reaction in that difficult patch, you crossed it safely. Have you thought about why this happened?

Let’s discuss this important topic, which is ‘anxiety’.

Some people think anxiety can bring stress and is harmful to our body, but a little anxiety is very important in our daily life to carry out some tasks safely or perform well in important situations. That anxiety prepares your body to recognize certain dangers and makes you alert and ready to tackle difficult situations.

The problem starts with anxiety when it takes the shape of a chronic condition, and you are continuously in anxiety and stress, fearing something or speculating about future harm.  It feels like an unwanted thing is following you throughout the day. Hence, anxiety comes under mental disorder and needs a a multifaceted approach for treatment like therapy, medications, support groups, and counseling. However, daily routine modification and addition and deletion of certain habits make a great difference in overcoming anxiety.

In this article, we will explore the top 5 daily habits that are beneficial for anxiety.

1) Mindful Morning Routine

Anxiety is high in the morning. People with anxiety generally wake with an increased heartbeat and excessive thoughts. This response is due to the hormone cortisol. Cortisol is considered to be a stress hormone, and its level is at its peak just after awakening early in the morning. This is called the cortisol awakening response. The anxiety in the morning makes the condition worse and feels overwhelming, as we suddenly remember everything as soon as we wake up, like responsibilities and deadlines. So, the first thing you do in the morning sets the mood for the entire day. Always wake up with a positive tone and with gratitude. These practices suddenly calm your thoughts. Gratitude is linked to lower stress levels, a good mood, and better health. Make yourself hydrated with water and breathe deeply; it makes you feel grounded. Make clarity of thoughts; write down the things you are doing in the day ahead. This practice sets the direction of the day as per priority so the things do not get cluttered, and you sort all the things in a good way.

2) Decrease Caffiene and Sugar

Caffiene is the stimulant which directly having excitatory effect on brain. It stimulate the brain, increased the heart rate, relentlessness and nervousness. By this way caffeine can accelerate the existing anxiety. Caffiene is also associated with panic attack. Caffiene can increase the panic attack in individual with panic disorder. Another effect of caffeine is on sleep; caffeine can disturb the sleep pattern, delaying in sleep or stay in sleep and lack of sleep is strongly associated with anxiety. Limiting the caffeine from coffee, soda and energy drinks leads to calmer feeling, increase sleep pattern and reduced anxiety.

Increased sugar intake is leads to fluctuation in blood sugar level, causing spiking and crashing in blood sugar level. When blood sugar level crashes, body releases hormone cortisol and adrenaline which cause anxiety. Hence moderating the use of sugar can significantly decrease the anxiety in individual.

3) Consistent Sleep

Getting consistent sleep for 7 to 8 hours daily can really help lower anxiety. When you go to bed and wake up at the same time every day, it keeps your brain chemicals balanced and helps control stress hormones like cortisol. This makes it easier for your brain to handle emotions and stay calm. Good sleep also helps your body relax, so you’re less likely to feel things like a racing heart that can make anxiety worse. Plus, having a regular sleep routine gives you a sense of control and stability, which can make you feel less stressed overall.

4) Healthy Diet

Eating healthy food can really help lower anxiety. The brain needs certain chemicals to feel calm and happy, and these chemicals are made from the nutrients we get from food. Foods with good proteins, vitamins, and healthy fats (like fish oil) help the brain work better and keep moods steady. Healthy foods like fruits, vegetables, nuts, and fish also fight swelling in the body, which can make anxiety worse if left untreated. Our stomach and brain are closely connected, so keeping our gut healthy by eating foods with fibre, yogurt, and fermented foods can also help reduce anxiety. It’s important to keep blood sugar steady because big ups and downs in sugar levels can make us feel more nervous and upset. Eating regular meals with whole grains, lean meats, and healthy fats can help. Sometimes, not getting enough important vitamins and minerals, like magnesium, vitamin D, and iron, can also make anxiety worse. Eating a variety of healthy foods helps avoid these problems. Some of the best foods to help with anxiety are leafy green vegetables, berries, fish like salmon, whole grains, nuts, seeds, beans, and foods with good bacteria like yogurt. It’s a good idea to avoid too much sugar, white bread, too much coffee, and alcohol because they can make anxiety worse. Overall, eating good food helps both the body and the mind feel better and stronger.

5) Regular Exercise

Exercise can be a very helpful way to feel less anxious. When you move your body, it releases chemicals that make you feel happier and calmer. Exercise also lowers the amount of stress hormones in your body, helping you feel more relaxed. Being active can help you sleep better, and good sleep often makes anxiety easier to handle. Exercise gives your mind a break from worrying by making you focus on what you are doing. Reaching small exercise goals can also make you feel more confident and in control. Some activities like yoga and swimming teach you how to breathe deeply, which can calm you down. Exercising with others can give you support and make you feel less alone. Overall, regular exercise is a simple and natural way to help manage anxiety.

References:

1.Anxiety disorders, 27 Sep 2023, World Health Organization

2. Szuhany KL, Simon NM. Anxiety Disorders: A Review. JAMA.2022;328(24):2431–2445. doi:10.1001/jama.2022.227444

3. 7 Mindful Morning Routines to Reduce Stress and Anxiety, Pacific Health Group, available from https://mypacifichealth.com/7-mindful-morning-routines-to-reduce-stress-and-anxiety

4. Klevebrant L, Frick A. Effects of caffeine on anxiety and panic attacks in patients with panic disorder: A systematic review and meta-analysis. Gen Hosp Psychiatry. 2022 Jan-Feb; 74:22-31. Doi: 10.1016/j.genhosppsych.2021.11.005. Epub 2021 Dec 2. PMID: 34871964.

5. Angela Jacques, Nicholas Chaaya, Kate Beecher, The impact of sugar consumption on stress driven, emotional and addictive behaviors, Neuroscience & Biobehavioral Reviews, Volume 103, 2019, Pages 178-199, https://doi.org/10.1016/j.neubiorev.2019.05.021

6. Sarah L. Chellappa, Daniel Aeschbach, Sleep and anxiety: From mechanisms to interventions, Sleep Medicine Reviews, Volume 61, 2022, 101583, https://doi.org/10.1016/j.smrv.2021.101583

7. Aucoin M, LaChance L, Naidoo U, et al, Diet and Anxiety: A Scoping Review. Nutrients. 2021 Dec 10;13(12):4418. Doi: 10.3390/nu13124418. PMID: 34959972; PMCID: PMC8706568.

8. Basso, M., Zorzan, I., Johnstone, N., Barberis, M., & Cohen Kadosh, K. (2024). Diet quality and anxiety: A critical overview with focus on the gut microbiome. Frontiers in Nutrition, 11, 1346483. https://doi.org/10.3389/fnut.2024.1346483

9. Anderson E, Shivakumar G. Effects of exercise and physical activity on anxiety. Front Psychiatry. 2013 Apr 23; 4:27. Doi: 10.3389/fpsyt.2013.00027. PMID: 23630504; PMCID: PMC3632802.

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Roche Secures FDA Breakthrough Device Designation for AI-Powered VENTANA TROP2 Diagnostic in Non-Small Cell Lung Cancer

by with No Comment New Drug Approval

Medically Written and Reviewed By Pavan Reddy (Biomedical Engineer)

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Roche said VENTANA TROP 2 is not only detect TROP 2 level on cell surface but it also detect exact level inside of the cancer cell (In image pathologist using VENTANA TROP 2 assay device) Source: Freepik.Com

Introduction: Roche’s New AI Tool

In an exciting step forward for cancer diagnosis, the U.S. Food and Drug Administration (FDA) have given Breakthrough Device Designation to a new tool developed by Roche. The tool is called the VENTANA TROP2 assay, and it uses artificial intelligence (AI) to detect and treatment stratification of lung cancer known as non-small cell lung cancer (NSCLC).

NSCLC is the most common form of lung cancer, making up about 85% of all lung cancer cases around the world. Roche’s test doesn’t just find cancer. It also helps to figure out the best treatment options for each patient by analyzing how the cancer behaves. This new AI-driven approach could lead to faster, more accurate diagnoses, and more personalized treatment plans, giving patients a better chance of successful treatment.

What Is TROP2 and Why Does It Matter?

TROP2 is a special kind of protein found on the surface of certain cells, including many cancer cells. It’s especially common in epithelial cancers, like non-small cell lung cancer (NSCLC). When a tumor has high levels of TROP2, it usually means the cancer is growing quickly and may lead to a poorer outcome for the patient. Because of this, TROP2 is considered an important biomarker a signal can use to better understand the cancer and choose the right treatment.

Unlike older companion diagnostic tests that only look at protein levels on the surface of cancer cells Roche’s VENTANA TROP2 assay uses artificial intelligence (AI) to measure exactly how much TROP2 is also present inside a tumor sample. This helps oncologists get very precise information about the cancer, which can guide them in choosing more targeted, effective therapies for each patient.

How the AI Tool Works: Powered by Digital Pathology

Roche’s VENTANA TROP2 (EPR20043) RxDx device is an immunohistochemistry (IHC) assay is part of a larger digital system called uPath, which is the company’s digital pathology platform. This platform is designed to look at complex tissue samples more easily and accurately.

By using advanced AI algorithms based image analysis with a level of diagnostic precision; uPath can analyze cancer cells more quickly and consistently than traditional methods. It reduces the chance of human error and helps ensure that results are reliable and repeatable. This means pathologists can make faster, more confident decisions about a patient’s diagnosis.

Implications for Personalized Medicine

The FDA’s Breakthrough Device Designation highlights the significant potential of Roche’s VENTANA TROP2 assay to enhance clinical outcomes for patients. This designation recognizes the assay’s ability to support more personalized and targeted treatment strategies, particularly for individuals with TROP2-positive cancers.

By accurately identifying patients who are most likely to respond to TROP2-targeted therapies, the assay enables oncologists to select the most effective treatment options from the outset. This can lead to higher response rates, improved survival outcomes, and a more efficient use of therapies in clinical practice.

Looking Ahead: Shaping the Future of Lung Cancer Diagnosis

As the VENTANA TROP2 assay continues through clinical validation and regulatory review, it shows strong potential to transform how non-small cell lung cancer (NSCLC) is diagnosed and treated. By offering more precise insights into tumor biology, the assay could become a powerful tool in guiding personalized cancer care.

This advancement also reinforces the growing importance of precision medicine an approach that tailors treatment to each patient’s unique disease profile. If successful, this assay could help set a new standard in how lung cancer is diagnosed and managed, leading to better outcomes for patients.

Reference

1. Roche granted FDA Breakthrough Device Designation for first AI-driven companion diagnostic for non-small cell lung cancer, 29 April 2025, Roche Diagnostic

2. Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation.Pathol Int. 2020;70(5):287-294.

3. Shvartsur A, et al. Trop2 and it’s over expression in cancers: regulation and clinical/therapeutic implications. Genes & Cancer. 2015 Mar; 6(3-4): 84-105.

4. Roche receives FDA breakthrough label for AI-powered lung cancer companion diagnostic test, 29 April 2025, fierce biotech, available from https://www.fiercebiotech.com/medtech/roche-receives-fda-breakthrough-label-ai-powered-lung-cancer-companion-diagnostic-test

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Gut-Brain Connection: Eisenbergiella tayi and Lachnoclostridium Intestinal Bacteria Linked to Multiple Sclerosis

by with No Comment Research

 Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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Source: Freepik.Com

Introduction: A Gut–Brain Connection in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease in which the body’s immune system mistakenly attacks the central nervous system, which includes the brain and spinal cord. This can lead to a range of symptoms, such as muscle weakness, coordination trouble, and vision or thinking problems. Scientists have known for a while that a person’s genes can play a role in increasing the risk of developing MS. However, in recent years, researchers have started looking closely at the gut microbiome. The vast community of bacteria and other tiny organisms living in our digestive system is a possible environmental factor that could help trigger the disease.

A new study, published in April 2025 in the journal PNAS (Proceedings of the National Academy of Sciences), provides the strongest evidence so far that certain types of gut bacteria might start changes in the body that lead to MS-like illness. This suggests that the microbes in our gut might do more than digest food, as they could also influence serious diseases like MS.

Unique Study Design: Learning from Identical Twins

To better understand how gut bacteria might be involved in multiple sclerosis (MS), researchers studied 81 pairs of identical twins, where only one of the two siblings had MS. Since identical twins share the same genes and usually grow up in very similar environments, this was a smart way to remove other factors and focus just on differences in their gut microbiomes. This helped the scientists look more closely at whether changes in gut bacteria might be related to the start of the disease.

The researchers used a method called 16S rRNA sequencing, which is a powerful tool for identifying and measuring different types of bacteria in the gut. When they compared the bacteria from the twins with MS to their healthy siblings, they found more than 50 types of bacteria (called microbial taxa) that were present in different amounts. One big finding was a noticeable increase in bacteria from a group called the Firmicutes phylum in the twins who had MS. Some of these specific bacteria had already been linked to MS in earlier studies, so this strengthens the idea that they might be involved in triggering or worsening the disease.

Going Deeper: Focusing on the Small Intestine

Most studies on gut bacteria usually analyze stool samples, which come from the large intestine. But this study took a different and more detailed approach. The researchers collected bacteria samples directly from various parts of the intestines, especially a specific area called the terminal ileum this is the last part of the small intestine, located just before the large intestine begins.

Why the terminal ileum? This part of the gut is known to be full of immune system activity, making it a key location where gut bacteria and immune cells closely interact. The researchers believed that certain bacteria living in this region might directly affect how immune cells behave, possibly in a way that could trigger the kind of immune response seen in MS.

By focusing on this area, the study aimed to find out if bacteria here have a stronger or more specific role in influencing the development of MS, compared to bacteria found in the lower parts of the gut

Transferring Human Gut Bacteria to Mice

To find out if the gut bacteria from people with MS could cause disease, the researchers did a special experiment. They took bacteria from the small intestine (specifically the terminal ileum) of the twins who had MS and put them into germ-free mice. These are special mice that are raised in a completely bacteria-free environment and have been genetically engineered to be more likely to develop a disease similar to MS, called EAE (Experimental Autoimmune Encephalomyelitis).

The results were surprising: mice that received bacteria from the MS-affected twins were much more likely to develop EAE compared to mice that received bacteria from the healthy twins. This strongly suggests that the gut microbes from people with MS can trigger disease in animals already genetically vulnerable to it.

Another important discovery: only the female mice got sick. This is especially interesting because MS is much more common in women than in men. So this part of the experiment not only supported the role of gut microbes in disease but also mirrored the gender pattern seen in human MS.

Key Bacteria Identified: The Lachnospiraceae Family

After studying the gut bacteria in the mice that got sick, the researchers were able to pinpoint two specific types of bacteria that seemed to play a big role: Eisenbergiella tayi and Lachnoclostridium. These bacteria belong to a larger group called the Lachnospiraceae family.

What’s interesting is that these bacteria are usually found in very small amounts in stool samples, so they had not received much attention in earlier studies. But in this study, they showed up clearly because the researchers sampled the small intestine, not just faeces.

In the mice that developed MS-like disease, these two species didn’t just appear they grew rapidly and took over large parts of the gut. Even more important, their presence was linked to changes in the immune system. Specifically, the mice had more inflammatory Th17 cells, which are a type of immune cell known to cause damage in MS. This suggests that these gut bacteria may be directly encouraging harmful immune activity that leads to the disease.

Why the Ileum Is Important

The small intestine, and especially a section called the ileum, plays a very important role in how the immune system learns to tell the difference between harmless and harmful substances. This part of the gut contains special immune structures called GALT (gut-associated lymphoid tissue). In this area, immune cells are constantly interacting with the bacteria and other microbes that live in the gut.

The researchers believe that the bacteria Eisenbergiella tayi and Lachnoclostridium may take advantage of this environment. These microbes could influence immune cells in the ileum in a harmful way, possibly by:

Molecular mimicry – this is when bacteria have molecules on their surface that look like parts of the body’s own cells. This can confuse the immune system and cause it to attack healthy tissue.

Inflammatory signalling – this means the bacteria might release substances that cause the immune system to become overactive or inflamed.

Either way, these interactions could activate T cells, a type of immune cell, and cause them to become autoimmune, meaning they start attacking the body’s nervous system, which is what happens in MS.

Why Females Were More Affected

One of the most interesting findings from the study was that only the female mice developed MS-like disease after receiving the gut bacteria from people with MS. This matches what we see in humans MS is about two to three times more common in women than in men.

The exact reason for this difference isn’t fully understood yet, but scientists think it may have to do with how female hormones or the female immune system interacts with certain bacteria. It’s possible that women’s bodies respond more strongly to gut bacteria that trigger inflammation, which could increase the chances of developing MS.

This part of the research highlights that sex differences may play a key role in how diseases like MS develop, especially when gut microbes are involved.

What This Could Mean for Future MS Treatments

If these findings are confirmed by more research, they could open the door to new ways of treating MS by focusing on the gut microbiome especially the harmful bacteria that may trigger the disease.

For example, future treatments might include:

Targeted probiotics (helpful bacteria) to crowd out the bad ones

Special antibiotics that remove only the harmful bacteria, like E. tayi and Lachnoclostridium

Diet changes that support a healthier gut and reduce inflammation

A New Approach to Understanding MS and Other Autoimmune Diseases

One important lesson from this study is the new method it used to analyze the gut bacteria. Instead of just looking at stool samples, which come from the large intestine, the researchers focused on bacteria taken directly from the small intestine. This is a big deal because it gives scientists a more detailed view of the gut microbiome and its role in diseases like MS.

This approach could be very helpful for studying other autoimmune diseases as well, not just MS. By analyzing the bacteria in different parts of the gut, researchers could get a better understanding of how these diseases develop and find more accurate ways to diagnose them. It might even lead to personalized treatments based on the unique microbiome of each patient.

Conclusion: A New Chapter in MS Research

This study marks a big step forward in understanding how gut bacteria might actually help cause multiple sclerosis (MS) not just be connected to it. By using a careful approach that included identical twin studies and germ-free mice experiments, the researchers were able to do more than just find suspicious bacteria. They showed that these microbes could trigger MS-like disease in the right conditions.

This research adds to the growing evidence of a strong link between the gut and the brain known as the gut–brain axis. As scientists continue to learn more about this connection, we may soon see new, safer, and more targeted treatments that work by adjusting gut bacteria. This could lead to better ways to prevent or manage autoimmune diseases like MS in the future.

References:

1.Altieri C, Speranza B, Corbo MR, Sinigaglia M, Bevilacqua A. Gut-Microbiota, and Multiple Sclerosis: Background, Evidence, and Perspectives. Nutrients. 2023 Feb 14;15(4):942. Doi: 10.3390/nu15040942. PMID: 36839299; PMCID: PMC9965298.

2. Hongsup Yoona, Lisa Ann Gerdesa , Florian Beigel et al, Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study, PNAS  2025  Vol. 122  No. 18 e2419689122, https://doi.org/10.1073/pnas.2419689122

3. Thirion, F., Sellebjerg, F., Fan, Y. et al.The gut microbiota in multiple sclerosis varies with disease activity. Genome Med15, 1 (2023). https://doi.org/10.1186/s13073-022-01148-1

4. Vinod K. Gupta h Guneet S. Janda, Heather K. Pump  Nikhil Lele et al, Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis, Neurology: Neuroimmunology & Neuroinflammation | Volume 12, Number 2 | March 2025

5. Correale, J., Hohlfeld, R. & Baranzini, S.E. The role of the gut microbiota in multiple sclerosis. Nat Rev Neurol18, 544–558 (2022). https://doi.org/10.1038/s41582-022-00697-8

6. Hindson, J. A possible link between multiple sclerosis and gut microbiota. Nat Rev Neurol13, 705 (2017). https://doi.org/10.1038/nrneurol.2017.142

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Reclaiming Life after Stroke: DDL-920 Shows Promising Results in UCLA Study

by with No Comment Research

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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Source: Freepik.Com

In a landmark study published in Nature Communications, University of California, Los Angeles (UCLA) researchers identified the first drug that is able to promote stroke rehabilitation by reestablishing connections between affected brain cells. Drug DDL-920, which specifically targets parvalbumin interneurons, a critical type of brain cell that has been affected during stroke and that plays a key role in neural circuit function and recovery after stroke.

Stroke

Stroke is a life-threatening condition where brain cells are damaged, depending on the severity of the stroke. Strokes are of two types: ischemic stroke and hemorrhagic stroke. However, a mild stroke does not affect the patient seriously, but severe ischemic and hemorrhagic strokes result in serious complications like loss of sensation in half of the body, which severely affects patients’ abilities to do activities of daily living (ADL). Hence, stroke is considered to be the leading cause of long-term disability, often leaving survivors with impaired motor functions.

One of the biggest challenges in the treatment of stroke is the inability of the brain to fully recover. This is because brain cells die during the stroke, and some connections between neurons are lost. These connections were unknown till date, which is why no treatments were developed in the past to restore these connections. Stroke patients were fully dependent on physical rehabilitation and other prophylactic medications to prevent further complications like seizures and infections.

What does the new research say

The UCLA team, led by Dr. S. Thomas Carmichael and Naohiko Okabe, researched to determine post-stroke brain rehabilitation science and possible pharmacological compounds that allow patients to recover the same as physical therapy does.

The first scientists discovered how the brain performs motor skills or motor activity post-stroke during physical therapy. Scientists have found out that to learn new motor skills, like pressing a lever, certain brain cells called interneurons form connections. It reduces connections made by one type of cell, called somatostatin interneurons, and increases connections made by another type of cell, called parvalbumin interneurons. This shows that different brain cells play special roles in helping people recover movement skills after a stroke, especially for complex tasks. However, scientists didn’t fully understand which brain circuits were involved, how important they were, or if a drug could copy the effects of rehabilitation therapy in the past. In this study, the scientist found that brain circuits involving parvalbumin interneurons and stroke-affected neurons help recovery by making brain activity more synchronized. These findings suggest possible drug targets that could mimic the effects of rehabilitation.

To understand the role of this type of neuronal circuit in functional recovery induced by rehabilitation, the scientist developed a mouse model to study how the brain functions during rehabilitation and how certain circuits, like the parvalbumin interneuron-stroke-affected neuron circuit, play a role in rehabilitation.

In this study, scientists knew that certain brain cells called parvalbumin interneurons connect more with stroke-affected neurons during rehabilitation, so they wanted to see if rehabilitation turns on this connection. To check this, scientists looked at whether rehabilitation causes changes in brain activity and flexibility in an area called RFA. Scientists did this by measuring special “activity” genes (Zif268 and FosB) and looking at structures called perineuronal nets, which can limit how flexible parvalbumin cells are. Scientists found that rehabilitation increased the activity of both types of neurons and made stroke-affected neurons even more active. Rehabilitation also made fewer parvalbumin cells covered by these nets, meaning they could change and adapt more easily. These results show that rehabilitation wakes up and boosts the flexibility of these brain circuits.

New pharmacologically active compound for stroke

As scientist discovered what are the things happened in brain during rehabilitation physical therapy and what are the circuits involved in it. Now scientist wants to check some pharmacological compounds which can target these sites and produce rehabilitation like effect.

Scientist tested two different compounds

AUT00201, which boosts the activity of certain proteins called Kv3.1 ion channels mostly found in Parvalbumin interneurons.

DDL-920, developed in UCLA lab of Varghese John, which reduces the activity of a specific type of GABA receptor called α1β2δ GABAAR that normally, slows down Parvalbumin interneurons.

The special GABA receptors scientist targeted are mainly found on Parvalbumin interneurons. They are different from similar receptors found on other brain cells like granule cells, pyramidal cells, or cerebellar cells.

Boosting Kv3.1 channels makes Parvalbumin interneurons fire faster and more efficiently. Reducing GABAARδ activity lowers the “brake” on these cells, making them more active. These changes help adjust the brain’s gamma Oscillation, which are important for many brain functions.

Scientist gave the drugs by mouth to make them easier to use in future treatments for people. Scientist confirmed that the targets of these drugs (Kv3.1 channels and GABAARδ receptors) are mainly present on Parvalbumin interneurons in both healthy and stroke-affected brains.

To see if the drugs activated Parvalbumin interneurons, they gave just one dose. As expected, both AUT00201 and DDL-920 increased the activity of a marker called Zif268 in Parvalbumin interneurons, showing that the cells became more active. However, only DDL-920 caused a significant increase.

In a stroke recovery study, scientist started drug treatments three days after the stroke happened. Then tested how well the animals could use their forelimbs to grab small pasta pieces and how well they could walk across a grid without slipping.

Neither drug caused bad side effects like weight loss or movement problems.

Animals that had strokes and were given either the vehicle (placebo) or AUT00201 had trouble picking up the pasta pieces.

In contrast, animals treated with DDL-920 completely recovered their ability to pick up the pasta.

Both drugs also helped the animals recover faster in the walking test.

Overall, these results show that drugs like these specially DDL-920 can help the brain heal after a stroke in a way similar to what is seen with physical rehabilitation.

Why This Discovery Matters 

Current post stroke treatment includes physical rehabilitation which relies heavily on physical therapy; however, full function of the body cannot be restored by this therapy. DDL-920 represents a paradigm shift by directly targeting the biological mechanisms of recovery. 

Dr. Carmichael, lead author and professor and chair of UCLA Neurology, said that “This is the first drug designed to repair neural circuits after stroke.” “Instead of just managing symptoms, we’re addressing the root cause of disability by helping the brain heal itself.” 

Next Steps: Clinical Trials and Future Applications 

The UCLA team is now preparing for human clinical trials, which could begin within the next two years. If successful, DDL-920 can become a cornerstone of post-stroke treatment, benefiting millions of survivors worldwide. Along with stroke, this newfound mechanism and new targets can be beneficial in treating other conditions, such as Traumatic brain injury (TBI), Spinal cord injuries, and Neurodegenerative diseases like Alzheimer’s and Parkinson’s 

Conclusion 

The development of DDL-920 marks a historic milestone in neuroscience and stroke rehabilitation. By unlocking the brain’s innate ability to rewire itself, this drug could transform recovery for stroke survivors, offering new hope where options were once limited. 

References:

1. UCLA discovers first stroke rehabilitation drug to re-establish brain connections in mice, UCLA Newsroom, 20 March 2025, available from https://newsroom.ucla.edu/releases/ucla-discovers-first-stroke-rehabilitation-drug-to-reestablish-brain-connections-in-mice

2. Okabe, N., Wei, X., Abumeri, F. et al. Parvalbumin interneurons regulate rehabilitation-induced functional recovery after stroke and identify a rehabilitation drug. Nat Commun 16, 2556 (2025). https://doi.org/10.1038/s41467-025-57860-0

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WHO 2025 Guidelines: Strategies to Prevent Adolescent Pregnancy in Low and Middle- Income Countries (LMICs)

by with No Comment Health Tidings

Medically Reviewed By Dr. Seema Satbhai BAMS, MPH, PHD (Public Health Expert)

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Introduction

Adolescent pregnancy is still a big health problem around the world, especially in low and middle-income countries. Every year, millions of young girls become mothers, which can harm their health and make it harder for them to finish school or have a better future. To help fix this, the World Health Organization (WHO) has made new guidelines and recommendations to prevent early pregnancies and protect young girls from its adverse effects.

The Scale of the Problem

Every year, about 21 million girls between the ages of 15 and 19 in LMICs countries get pregnant, and about half of these pregnancies are not planned or intentional. In 2021, over 12 million girls aged 15 to 19 and nearly 500,000 girls aged 10 to 14 gave birth. These numbers show that we need to take action, especially in places like sub-Saharan Africa and Latin America, where adolescent pregnancy is most common.

Health and Social Consequences

Adolescent girls who become mothers have a higher chance of facing serious health problems during pregnancy and childbirth. Their babies are also at greater risk of infant mortality. Early pregnancy can also cause big problems in their lives many girls have to leave school, find it harder to get a good job, and may stay poor. Child marriage makes things worse, as young brides often have many pregnancies, feel stressed or sad, and have less control over their own lives.

Underlying Causes of Adolescent Pregnancy

There are many reasons why adolescent pregnancy is common in LMICs’ countries:

Child Marriage: In some cultures, girls are expected to marry before they turn 18, which often lead to early pregnancy.

Lack of Education: Girls who don’t go to school or drop out early are more likely to become pregnant. Education helps them to acquire knowledge of self protection and important skills that can delay marriage and pregnancy.

Poor Access to Health Services: Many adolescents can’t get proper sexual and reproductive information, birth control, or information about their body and their rights.

Gender Inequality: In some places, girls don’t have a community among themselves, which reduces their ability to make informed decisions about sex and contraception.  

Sexual Abuse: Some adolescent pregnancies happen because of forced sex or abuse, which puts girls in even more danger.”

Progress and Remaining Challenges

There has been some good progress in the last 20 years. The number of adolescent births around the world was declined by 34% from 2000 to 2021, and child marriage dropped by 24% between 2010 and 2020. This happened because of better education about sex, community support, and helpful government policies.

But not everyone is seeing these improvements. Girls who live in rural areas, have little education, or come from low-income families are still at risk. Weak health systems and missing policies are still making it hard for many girls to get the help they need.

WHO’s Updated Recommendations

The World Health Organization (WHO) knows there has been progress and many challenges. So, in its new 2025 guideline, WHO suggests two main ways to help

1. Recommendations to Reduce Child Marriage and help married girls

Rec. 1: Teaching girls’ important skills, building their knowledge, assets and build support from society.

Rec 2: WHO recommended the programmes which aims to reduce child marriages and supporting married girls by involving parents and guardians and especially boys and men and subsequently involving broader community to create and sustain gender equitable environment in society.

Rec 3: WHO recommended giving conditional rewards for girls who at the highest risk of child marriage to increase or extend their school attainment and delay marriage as a part of broad strategy under social protection interventions.

Rec 4: WHO recommended removing gender related obstacle and making sure girls can go to school for at least 12 years and get quality education.

Rec 5: WHO recommended that the adolescent girls should be economically empowered by increasing their financial literacy, knowing the importance of savings and access to employment skills that can expand their alternative options to marriage before turning 18.

Rec 6: WHO recommended creating laws and policies that restrict marriages in general before the age of 18. These laws and policies should be uniform with the standards of human rights.

2. Better Access to Birth Control (Contraceptives)
To improve adolescents’ use of contraceptives, WHO suggests:

Rec 1: WHO recommends programs that help adolescents challenge harmful gender norms and build confidence so they can make informed choices about using contraception.

Rec 2: WHO recommends programs that change unfair gender and social rules to help adolescents make their own choices about contraception and to make it easier for them to get and keep using it.

Rec 3: People of reproductive age should have the option to give themselves injectable contraception as another way to access it.

Oral contraceptive pills (OCPs) should be available without a prescription for people who use them.

Emergency contraceptive pills should be available without a prescription for anyone who wants to use them.

Women should be able to get up to a one-year supply of contraceptive pills based on their needs and preferences. Programs should make sure pills are easy to get while also managing supplies well. The system should be flexible so women can get the amount they need when they need it.

Rec 4: WHO recommends taking steps to lower the cost of contraception so that adolescents can afford to start using it and keep using it.

Rec 5: WHO recommends using accurate and safe digital health tools for adolescents as part of sexual and reproductive health programs

Good Practice Statement

Apart from recommendations, WHO has given some good practice statements to prevent child marriages and adolescent pregnancies and better access to contraceptives.

  1. Important leaders like those in politics, government, religion, and local traditions should be encouraged to help stop child marriage and support girls’ rights. These people are even encouraging access to, use of, and continued use of contraception among adolescents.
  2. Efforts to support women and girls should also include the specific needs and rights of girls who are married or living with a partner, whether formally or informally.
  3. Adolescents, including those who are married or living with a partner, should be actively involved in planning, designing, and reviewing programs that support their needs and rights.
  4. Programs to improve the quality of health services should be put in place to help adolescents access, start using, and continue using contraception.
  5. Laws and policies about age, marriage, and consent should be clear and supportive so that adolescents can access sexual and reproductive health services and contraceptives more easily and keep using them.
  6. Adolescents should be actively involved in planning, carrying out, and reviewing programs that support their contraceptive needs and rights.

Global and Local Implementation

The new WHO guidelines highlight that every country and community is different, so plans should be made to fit local needs. WHO is working with other groups like United Nations Population Fund (UNFPA), Girls Not Brides, and Family Planning 2030 to help governments in

Running awareness campaigns

Training local workers and leaders

Giving expert help and advice

Sharing successful ideas and strategies that have worked in other places

Conclusion

Preventing adolescent pregnancy is not only a health priority but also a matter of equity and human rights. Investing in adolescent girls’ education, empowerment, and access to quality health services is essential for building healthier and more resilient community. When girls get a good education, learn about their bodies, and feel confident, they can make better choices for their lives. WHO’s guidelines give countries a clear plan to help every adolescent girl live a healthier, safer, and better life.

References:

WHO releases new guideline to prevent adolescent pregnancies and improve girls’ health, 23 April 2025, World Health Organization

WHO guideline on preventing early pregnancy and poor reproductive outcomes among adolescents in low- and middle-income countries. Geneva: World Health Organization; 2025. Licence: CC BY-NC-SA 3.0 IGO.

Adolescent pregnancy, 10 April 2024, World Health Organization

Emergency contraception, 09 November 2021, World Health Organization

Crooks R, Bedwell C, Lavender T. Adolescent experiences of pregnancy in low-and middle-income countries: a meta-synthesis of qualitative studies. BMC Pregnancy Childbirth. 2022 Sep 12; 22(1):702. Doi: 10.1186/s12884-022-05022-1. PMID: 36096763; PMCID: PMC9469636.

Sabet, Farnaz et al., The forgotten girls: the state of evidence for health interventions for pregnant adolescents and their newborns in low-income and middle-income countries, The Lancet, Volume 402, Issue 10412, 1580 – 1596

Navideh Noori, Joshua L Proctor, Yvette Efevbera, Assaf P Oron – The Effect of Adolescent Pregnancy on Child Mortality in 46 Low- and Middle-Income Countries: BMJ Global Health 2022;7:e007681.

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Google’s TxGEMMA: A Game-Changer for Cost-Effective and Accelerated Drug Development| How It Builds on TxLLM and Powers Agentic-Tx

by with No Comment Disease & DrugsResearch

Written By: Lavanya Chavhan B.Pharm

Reviewed By: Vikas Londhe M.Pharm (Pharmacology)

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Google DeepMind has launched TxGEMMA in the Google’s Health-Check Up event in New York concluded on 18 March 2025. TxGEMMA is a groundbreaking large language model (LLM) designed to transform conventional drug discovery and development. It is built on the success of TxLLM and forms the foundation for its new agent-based platform, AgenticX. TxGEMMA has the potential to significantly reduce the costs and timelines of the research and approval of the latest medicine. 

What Is TxGEMMA?

Therapeutics GEMMA abbreviated as TxGEMMA is a highly specialized language model trained for a strong focus on biomedical data, specifically drug discovery. TxGEMMA is not general LLMs but is tailored to understand the gradation of biological pathways, molecular structures, clinical trial data, and pharmaceutical development processes.

Features of TxGEMMA includes

Fine-tuning for biomedical tasks: TxGEMMA learns from a wide range of high-quality information that is important for discovering new drugs. This includes both publicly available data and private, carefully selected sources. For example, it studies scientific articles from PubMed, which is a large database of medical research papers. It also uses chemical databases that contain information about different molecules and how they behave. In addition, it looks at clinical trial registries, which track the progress and results of medical studies on new treatments, and biomedical patents, which describe new inventions in medicine. By learning from all these trusted sources, TxGEMMA gains a deep understanding of the science behind drug development.

Open-weight accessibility: One of the special things about TxGEMMA is that its creators plan to make its weights (key numbers, the model learns during training) available to the public. These weights are what allow the model to understand and make decisions based on the data it has studied. By sharing them openly, anyone can use, study, and even improve the model. This is different from many other AI models, especially those made by private companies, where the weights are kept secret and only the company can use them. Google’s decision to release TxGEMMA’s weights publically supports and encourages more people from universities, hospitals, and pharmaceutical companies to work together. This can speed up scientific progress and lead to better treatments for patients.

Multi-modal capabilities: In the future, TxGEMMA is expected to become even more advanced by including different types of biological data, not just written or textual information. This means it will be able to work with things like molecular images pictures of molecules at the microscopic level and genomic sequences, which are the complete sets of DNA instructions in living organisms. By combining these various types of data, TxGEMMA will become a multi-modal model, meaning it can understand and learn from many different kinds of biological information at the same time. This will make it much more powerful and effective in discovering new treatments and therapies for diseases.

Conversational AI for Deeper Drug Discovery Insights:

In addition to making predictions, TxGEMMA also comes in special versions designed for conversation called the 9B and 27B chat models. These versions have been instruction-tuned, which means they have been trained to understand and respond to detailed questions and commands, similar to having a knowledgeable research assistant you can talk to. With these chat models; scientists can have in-depth conversations with the AI. For example, they can ask complicated questions about biology or drug development, get clear explanations for why the model thinks a certain molecule might be harmful or helpful, and even carry on an exchange discussion to explore an idea more deeply. This makes the research process more transparent and interactive, helping scientists better understand the model’s reasoning and use its insights more confidently in their work.

TxGEMMA: A Successor of TxLLM

Before TxGEMMA, DeepMind released TxLLM in October 2024, an early experiment focused on translating language modeling capabilities to drug discovery applications. TxLLM proved that LLMs could expressively suggest new molecular targets, predict drug interactions, and assist in clinical trial design. However, TxLLM had some limitations like;

Limited domain-specific optimization

Closed or restricted access for external researchers

Performance bottlenecks when dealing with multi-step drug development workflows

TxGEMMA answered and addressed all these issues with more extensive, focused biomedical training, open weights, and it has ability to be integrated into larger agentic systems like Agentic-Tx.

Agentic-Tx

TxGEMMA is not a standalone model; it is also a part of Agentic-Tx, Google’s new agent-based framework for biomedical research. Agentic-Tx enables multiple AI agents each fine-tuned for specific tasks like target identification, compound optimization, and toxicity prediction, to collaborate intelligently and autonomously.

The Agentic-Tx framework is a smart and powerful system built to improve how scientists do biomedical research, especially when it comes to understanding diseases and finding new treatments. It works like an intelligent assistant that uses large language models (LLMs) advanced AI systems that can understand and generate human-like text. But Agentic-Tx goes even further by combining these language models with up-to-date biomedical knowledge and the ability to think through complex problems step by step. This means it can search for the latest biomedical information, analyze it carefully, and then use that knowledge to suggest treatments that are tailored to a specific patient’s needs. This kind of system has the potential to make drug discovery faster and more accurate.

Agentic-Tx is equipped with 18 tools, including:

TxGemma as a tool for multi-step reasoning

General search tools from PubMed, Wikipedia and the web

Specific molecular tools

Gene and protein tools

Agentic-Tx is positioned to:

Shorter discovery timelines: It helps speed up the early stages of research by automatically generating hypotheses and assisting with preclinical testing, saving valuable time.

Lower costs: By making better predictions early on, TxGEMMA reduces the need for repetitive lab experiments, cutting down on expenses.

Greater innovation: The model can identify new drug targets that traditional methods might overlook, opening the door to breakthrough treatments.

Why TxGEMMA Matters

The process of developing new medicines has become extremely expensive and slow for the pharmaceutical industry. A study in 2020 found that, on average, it costs more than $2.6 billion and takes over 10 years to bring just one drug to the market. This long timeline and high cost make it very difficult to discover new treatments. However, using advanced models like TxGEMMA could help solve some of these challenges. For example, TxGEMMA can help scientists quickly find molecules that are most likely to become effective drugs. It can also make better predictions about whether a compound will be safe and actually work in treating a disease. In addition, it can assist in designing smarter clinical trials that are more likely to succeed, reducing wasted time and resources. Because TxGEMMA’s model weights are openly shared, researchers all around the world from universities to small biotech companies can test, improve, and build on it. This openness could make drug discovery more accessible to everyone, not just large, wealthy pharmaceutical companies.

Conclusion

Google’s TxGEMMA, when used alongside AgenticX and based on the earlier advancements of TxLLM, marks a major turning point in how artificial intelligence can support drug development. This combination of powerful tools represents a paradigm shift a big change in the way things are done in the world of biomedical research. As the challenges of high costs, long timelines, and complex data continue to slow down traditional drug discovery, more scientists are turning to AI for help. Models like TxGEMMA offer a new way forward by making the process faster, more efficient, and more accessible. With continued development and global collaboration, these AI tools could lead to quicker discoveries, more effective treatments, and ultimately, a healthier future for everyone

References:

1. Introducing TxGemma: Open models to improve therapeutics development, Shekoofeh Azizi, 25 March 2025 available from https://developers.googleblog.com/en/introducing-txgemma-open-models-improving-therapeutics-development/

2. Eric Wang, Samuel Schmidgall, Paul F. Jaeger et al, TxGemma: Efficient and Agentic LLMs for Therapeutics, TxGEMMA report available from https://storage.googleapis.com/research-media/txgemma/txgemma-report.pdf

3. Tx-LLM: Supporting therapeutic development with large language models, Eric Wang, 09 October 2024, available from https://research.google/blog/tx-llm-supporting-therapeutic-development-with-large-language-models/

4. TxGemma, Health AI developer foundation, available from https://developers.google.com/health-ai-developer-foundations/txgemma#agentic_orchestration

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Ayurveda and Abhyanga: The Healing Power of Daily Massage

by with No Comment LifestyleWellness

Medically Written and Reviewed by Ayurvedacharya Dr. Gaurav Pathare (BAMS)

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Abhyanga, the application of medicated oils to the body, holds a significant place in Ayurveda as a vital part of the daily regimen. In today’s fast-paced world, where time is often scarce, it’s easy to overlook the importance of self-care. However, Ayurveda teaches us that maintaining health is just as important as managing time. The core principle of Ayurveda, as captured in the saying “Svasthasya Swasthya Rakshanam, Aturasya Vikar Prashamanam,” means “the protection of the health of a healthy person and the alleviation of the ailments of a sick person.” To support this, Ayurveda suggests following a daily regimen (Dinacharya) and seasonal regimen (Ritucharya), with Abhyanga being a major component.

Abhyanga in Ayurveda

Abhyanga is traditionally performed by applying medicated oils to the body, with sesame oil being most commonly used due to its beneficial properties. The oils are often infused with herbs tailored to balance specific doshas (body energies). According to Vagbhatacharya, an ancient Ayurvedic sage, “Abhyangamacharenityam” (abhyanga should be performed regularly), emphasizing its importance in maintaining health. While daily abhyanga may not be feasible in the modern world due to time constraints, it is advised to perform it at least once a week or even once a month for its many benefits.

In contemporary wellness practices, Abhyanga is often referred to as a “Rejuvenation Massage.” This type of massage can be done by oneself, but for maximum benefits, it is best performed by trained therapists and under the guidance of an Ayurvedic physician. A trained practitioner can tailor the oils and techniques to your individual dosha and health conditions. The therapist also knows the correct pressure to apply to specific parts of the body and the duration for which each area should be massaged.

Specific Areas for Abhyanga

Vagbhatacharya specifically highlights the importance of massaging the head, feet, and ears. These areas are particularly sensitive and are prone to Vata dosha imbalances. Vata dosha governs bodily functions like movement, communication, and flexibility, and when it is aggravated, it can lead to dryness and stiffness in the body. To balance this, oils infused with Vata-pacifying herbs are used, giving the oil a thicker consistency to counteract the dryness associated with an aggravated Vata.

Benefits of Abhyanga

Abhyanga provides a wide range of benefits, including

Anti-Aging: Reduces the effects of aging (Jara), promoting youthfulness.

Improved Vision: Enhances eyesight (Drishtiprasadak)

Increased Vitality: Boosts overall body strength (Pushti) and vigor

Relaxation and Sleep: Helps in achieving restful sleep (Swapna) and reduces fatigue (Shrama)

Strengthens the Skin: Makes the skin soft and smooth (Sutvakva)

Balances Vata Dosha: Reduces the effects of excess Vata in the body (Vataha)

Increased Longevity: Supports long life (Longevity benefits)

Vagbhatacharya further emphasizes that regular Abhyanga enhances mental clarity, physical strength, and overall vitality, ensuring better health and well-being.

Who Should Avoid Abhyanga

While Abhyanga is highly beneficial for most people, certain individuals should avoid it

People with Kapha-related diseases: Kapha imbalances result in conditions like obesity, respiratory issues, and excess mucus.

Post-purification individuals: Those who have undergone cleansing treatments like

Vamana (therapeutic vomiting) or Virechana (therapeutic purgation).

People with indigestion: Those suffering from Ajeerna (poor digestion) should refrain from Abhyanga until their digestive health improves.

Post-Abhyanga Care

After performing Abhyanga, it is important to rest for at least 30 minutes to allow the oils to be absorbed and to avoid any exposure to wind or cold. This rest period helps the body fully absorb the medicinal properties of the oils and enhances the overall effectiveness of the treatment.

Conclusion

In today’s stressful and hectic lifestyle, Abhyanga offers a simple yet effective solution to promote health and well-being. Even if daily practice is not always possible, incorporating it into your routine weekly or monthly can lead to significant benefits. Taking the time to care for your body through Abhyanga can lead to better physical and mental health, improved vitality, and a more balanced life.

Reference

Ashtang Hridaya chapter 2 / 7

 

Chlorotonil

A New Hope Against Antibiotic Resistance: Dual Mechanism in Chlorotonils Identified

by with No Comment Disease & DrugsResearch

Written By: Pragati Ekamalli, B.Pharm

Reviewed By: Vikas Londhe M.Pharm (Pharmacology)

Chlorotonil

Introduction

The increase of pathogens that resist multiple drugs is a big danger to global health, making many common antibiotics useless. In an important finding, scientists from Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) have discovered the dual mechanism of action of previously known natural antibiotic called chlorotonils that work against resistant bacteria. This study, published in Cell Chemical Biology, offers new ways to fight infections that do not respond to other antibiotics

Discovery of Chlorotonils

In 2008, a group of researchers from HIPS found something interesting while looking for new antibiotics in soil bacteria. They discovered chlorotonils, the substances taken from a type of soil bacteria called Sorangium cellulosum. Chlorotonils are known for fighting bacteria, especially tough ones like Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococci (VRE) and the malaria-causing parasite Plasmodium falciparum. They have a special ring shape and contain several chlorine atoms that help them work against bacteria.

However, chlorotonils are hard to dissolve and not very stable, which makes it difficult to turn them into medicines that’s why scientists later synthesized derivatives called dehalogenil to improve its properties, but so far, they have not been used in treatments.

Dual-Action Mechanism: How Chlorotonils Work

Researchers led by Dr. Jennifer Herrmann and Prof. Rolf Müller have found out how chlorotonils work. Unlike most antibiotics, chlorotonils attack bacteria in two ways. First, they attach to the bacteria’s cell wall and cause lipid-targeted membrane depolarization making it weak by causing uncontrolled efflux of potassium ions out of cell. On the other hand chlorotonil functionally inhibit two enzymes a membrane bound phosphatase YbjG and the cytoplasmic methionine amino peptidase MetAP which help the bacteria build their cell wall and proteins.

Dr. Felix Deschner, the main author of the study, explains that when chlorotonils attach to the cell membrane, potassium ions leak out of the cell. This messes up the cell’s internal balance, affecting its functions and pressure. These effects can kill bacterial cells.

By blocking the enzymes phosphatise YbjG and methionine amino peptidase MetAP at the same time; chlorotonils seriously harm the cell’s abilities to produce certain proteins required for cell to live and function, leading to its death.

This two-part approach also explains why chlorotonils work quickly. They quickly disrupt the cell membrane, making it hard for bacteria to resist. Unlike some traditional antibiotics that target specific enzymes where bacteria can adapt by making more enzymes or structurally changing the enzyme, chlorotonils’ varied attack makes it tougher for bacteria to develop resistance.

Overcoming Multidrug Resistance

The new antibiotic Chlorotonil is better than traditional antibiotics because it works in two ways, making it a strong option against antibiotic resistance bacteria.

Regular antibiotics usually focus on single bacterial function like cell wall synthesis. Bacteria can evolve our self through these challenges by doing single mutation in the target pathway.

Chlorotonil, on the other hand, attacks bacteria in two different ways. This means bacteria need to change in two places at the same time to become resistant, which is much less likely to happen. This makes it harder for bacteria to fight back.

However the dual action of Chlorotonil helps each other, making it effective even without combining it with other antibiotics. This makes treatment simpler than using several antibiotics at once.

Implications and Future Research

Researchers at the Helmholtz Centre for Infection Research (HZI) and the Hans Knoll Institute (HKI) are actively advancing the development of chlorotonil-based compounds, particularly focusing on a derivative named dehalogenil. This compound has demonstrated potent activity against both sexual and asexual stages of the malaria parasite Plasmodium falciparum, with no observed resistance under laboratory conditions.

In addition to malaria, chlorotonil derivatives are being investigated for their efficacy against persistent intestinal pathogens like Clostridioides difficile. Studies have shown that chlorotonil A (ChA) can effectively combat dormant stages of C. difficile, which are often resistant to conventional antibiotics, and does so with minimal disruption to the gut microbiome.

The future prospects for researchers at HZI and HKI include advancing dehalogenil through preclinical development, exploring its potential against other resistant pathogens, and collaborating with clinical partners to assess its efficacy in human trials. These efforts are supported by funding from initiatives like GO-Bio initial and the German Center for Infection Research (DZIF), which aim to translate promising compounds into viable therapeutic options.

Conclusion

As antibiotic resistance escalates, innovative solutions like chlorotonils offer hope. Their dual-action mechanism presents a robust strategy against MDR pathogens, reinforcing the importance of natural products in drug discovery. With further research, chlorotonils could become a critical weapon in the fight against superbugs.

References

1. Deschner, Felix et al., Natural products chlorotonils exert a complex antibacterial mechanism and address multiple targets, Cell Chemical Biology, Volume 0, Issue 0, available from https://www.cell.com/action/showPdf?pii=S2451-9456%2825%2900095-9

2. Chlorotonils: Naturals antibiotics’ dual-action mechanism against multidrug-resistant pathogens uncovered, Phys Org, 15 April 2025, available from https://phys.org/news/2025-04-chlorotonils-naturals-antibiotics-dual-action.html

3. W. Hofer, F. Deschner, G. Jézéquel, L. Functionalization of Chlorotonils: Dehalogenil as promising lead compound in vivo application, Angew. Chem. Int. Ed. 2024, 63, e202319765.  https://doi.org/10.1002/anie.202319765

4. Chlorotonil: Game-Changer in the Fight against Multidrug-Resistant Pathogens, Helmholtz Centre for Infection Research, 15 April 2025, available from https://www.helmholtz-hzi.de/en/media-center/newsroom/news-detail/chlorotonil-game-changer-in-the-fight-against-multidrug-resistant-pathogens/