Disease & Drugs -

Written By Lavanya Chavhan B.Pharm

Reviewed and Fact Checked By Vikas Londhe M.Pharm (Pharmacology)

Microplastics and nanoplastics (MNPs) tiny particles resulting from the degradation of plastic materials have rapidly become a focus of global health research. Two landmark studies published in Nature Medicine and The New England Journal of Medicine (NEJM) offer critical insights into the bioaccumulation and health consequences of these particles in human tissues. Together, they present an urgent call to re-evaluate the long-term implications of environmental plastic pollution.

Brain Accumulation and Neurological Concerns: Findings from Nature Medicine

A study published in Nature Medicine (April 2025) examined the presence of MNPs in human tissues, with a focus on liver, kidney, and brain samples from autopsies conducted in 2016 and 2024. The researchers used advanced analytical techniques including pyrolysis gas chromatography mass spectrometry (Py-GC/MS), electron microscopy, and Fourier-transform infrared spectroscopy to identify and quantify plastic particles.

Key Findings

Ubiquitous Presence: MNPs were detected in all three organs, but brain tissues exhibited the highest concentrations, 7 to 30 times greater than liver or kidney.

Polyethylene (PE) Dominance: PE accounted for approximately 75% of the plastic content in brains.

Temporal Trends: There was a significant increase in plastic concentrations between 2016 and 2024, reflecting rising environmental exposure.

Dementia Link: Brains of individuals with documented dementia had markedly higher levels of MNPs up to 26,076 µg/g suggesting a possible connection with neurodegenerative processes

Tissue Localization: Nanoplastics were found in brain parenchyma, immune cells, and cerebrovascular walls, raising questions about blood-brain barrier integrity and inflammatory responses.

Conclusion: Although the study does not establish causality, it strongly suggests that chronic exposure to MNPs may be associated with neurological vulnerability. The findings warrant deeper exploration into how plastic particles reach and affect brain tissue, particularly in individuals with compromised neurological health.

Cardiovascular Risks and Atheroma Infiltration: NEJM Study

The NEJM study (March 2024) provided the first direct clinical evidence linking MNPs to cardiovascular risk. It was a multicenter, prospective study involving 304 patients undergoing carotid endarterectomy for asymptomatic carotid artery disease.

Key Findings:

MNP Detection: In 58.4% of patients, polyethylene was found within atherosclerotic plaques. Polyvinyl chloride was also detected in 12.1%.

Nanoplastics Inside Plaques: Electron microscopy revealed jagged-edged particles (<1 µm) embedded in foam cells and extracellular plaque matrix.

Increased Cardiovascular Events: Over a 34-month follow-up, patients with MNP-positive plaques were at 4.5 times greater risk of myocardial infarction, stroke, or death compared to those without detectable plastics.

Inflammation Correlation: Elevated levels of interleukin-1β, IL-6, TNF-α, and CD68 were observed in MNP-positive plaques, suggesting heightened inflammatory responses.

Conclusion: The presence of MNPs in vascular tissues appears to be more than incidental. It correlates with both histological inflammation and clinically significant cardiovascular outcomes. This raises red flags about MNPs as emerging risk factors in heart and vascular diseases.

Implications for Human Health and Future Research

The convergence of findings from brain and vascular tissues paints a concerning picture:

Bioaccumulation is Organ-Specific: MNPs preferentially accumulate in certain tissues, potentially due to local physiological characteristics like vascular density or barrier permeability.

Health Impact is Multisystemic: While one study implicates MNPs in neurodegeneration, the other links them to cardiovascular events two of the most pressing areas in public health.

Mechanistic Gaps Remain: Both studies acknowledge the limitations in establishing causality. The exact pathways of MNP absorption, translocation, and clearance in humans remain poorly understood.

Another small study presented in American Heart Association conference

At the American Heart Association’s Vascular Discovery Scientific Sessions held in Baltimore on April 22, 2025, researchers presented compelling evidence linking microplastics to vascular disease. The study, led by Dr. Ross Clark from the University of New Mexico, analyzed carotid artery plaques from individuals who had experienced strokes, mini-strokes, or transient vision loss. Findings revealed that these plaques contained microplastics at concentrations 51 times higher than those in healthy arteries. Notably, polyethylene and polyvinyl chloride were the predominant plastics detected. While the study did not establish a direct causal relationship, it highlighted a strong association between microplastic accumulation and symptomatic arterial disease, underscoring the need for further research into the potential health impacts of environmental plastic exposure.

Conclusion

As plastic production continues to grow rapidly across the globe, recent studies serve as a strong warning that we must take urgent action. This includes putting better regulations in place, increasing scientific research, and raising public health awareness. Tiny plastic particles known as microplastics and nanoplastics are now found in the air we breathe, the food we eat, and even in our bodies. These particles may carry harmful chemicals and can travel through the blood stream to vital organs. Over time, long term exposure to them could increase the risk of serious health problems, including disease of the brain, heart, lungs and more.

To truly understand how these plastics affect our health, we need experts from many different fields to work together. Toxicologists can study how the plastics interact with our cells, neurologists can explore their impact on the brain and nervous system, cardiologists can look into heart-related effects, and environmental scientists can track how plastics move through ecosystems and into our bodies. Only through this kind of teamwork can we begin to understand plastic’s full impact on human health now and in the future.

Reference

Alexander J. Nihart, Marcus A. Garcia, Eliane El Hayek et al, Bioaccumulation of microplastics in decedent human brains, nature medicine, Volume 31 , April 2025, 1114–1119, https://doi.org/10.1038/s41591-024-03453-1

2. R. Marfella, F. Prattichizzo, C. Sardu et al, Microplastics and Nanoplastics in Atheromas and Cardiovascular Events, N Engl J Med 2024;390:900-10. DOI: 10.1056/NEJMoa2309822

3. Micronanoplastics found in artery-clogging plaque in the neck, American Heart Association Meeting Report , Scientific Conferences & Meetings, Stroke News & Brain Health, 22 April 2025 available from https://newsroom.heart.org/news/micronanoplastics-found-in-artery-clogging-plaque-in-the-neck

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How MIT’s SLIM Microcrystal Injection Technology is Transforming Long-Acting Treatments for HIV and Contraceptives

May 13, 2025

by official.ajinkya11@gmail.com with No Comment Research

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

MIT scientists have developed a self-injectable, long-acting drug delivery system using microcrystals. Learn how this innovation could transform contraception and chronic disease treatment.

Imagine a single injection that lasts for months, delivered through a tiny needle you can use yourself, no surgery, no hospital visit. Thanks to a groundbreaking innovation from researchers at Massachusetts Institute of Technology (MIT), that future is now one step closer.

MIT researchers have introduced a groundbreaking innovation that could make this vision a reality. Called SLIM; Self-aggregating Long-acting Injectable Microcrystals this new drug delivery system offers extended release, smaller needle size, and high drug potency, all packed into a single self-administered injection.

A New Way to Take Medicine: Once Every Few Months

Researchers at MIT and Harvard-affiliated Brigham and Women’s Hospital have developed a new drug delivery system called SLIM, short for Self-aggregating Long-acting Injectable Microcrystals.

Instead of needing large needles or surgery, SLIM allows medicine to be injected just under the skin through a tiny needle. Once injected, the medicine automatically forms a small solid “implant” that slowly releases the drug over several months.

This method is especially promising for medications like birth control and HIV medicine where convenience, privacy, and reliability are essential

Global Health Impact

For millions worldwide especially women in under-served regions SLIM could mean:

No need for surgical implants or repeated clinic visits

Empowered self-administration of essential medications

Lower costs and better access to long-term contraception

This new technology is published in the journal Nature Chemical Engineering. The technology also aligns with public health goals from organizations like the WHO and the study is co-funded by Gates Foundation.

How It Works: Tiny Crystals, Big Impact

SLIM works by suspending drug particles called microcrystals in a liquid. When injected into the body, this liquid mixes with the body’s water and causes the particles to clump together into a compact, slow-dissolving depot.

Less pain, smaller needles: Unlike other long-acting injections that require thick, painful needles, SLIM uses fine needles as small as 30 gauge (about the width of a human hair).

Fewer additives: Most long-acting shots rely on lots of added slowly degrading polymers such as polylactic acid or polycaprolactone to slow down drug release. SLIM only needs a tiny amount, reducing risks of side effects and injection pain.

Why It Matters: Especially for Women and Low-Resource Settings

In many parts of the world, women may not have easy access to clinics for repeated contraception or medications. Self-injectable treatments could empower them to take control of their health privately and conveniently.

This is a big step beyond current injectables like Depo-Provera, which lasts 3 months but can’t match the long-lasting protection of surgical implants like Nexplanon. SLIM offers the best of both: long-lasting protection with no surgery required.

A Breakthrough for Contraceptive Delivery

The researchers tested SLIM using levonorgestrel, a common hormonal contraceptive. In lab studies on rats, the SLIM formulation:

In early tests, the SLIM injection worked really well. After being injected, it formed a small, solid implant under the skin that stayed in place. It released the medicine much more slowly up to 5.6 times slower than current options, helping it last longer. The implant stayed strong and stable for over 3 months, and the injection was easy enough to be done at home using a regular small syringe. This means that women could get fewer injections while still having reliable, long-term birth control.

Bottom Line: Why This Matters for the Future of Medicine

The researchers plan to test SLIM with other drugs, especially those that are hard to dissolve in water, like many modern medications.

They’re also studying how to fine-tune drug release and improve safety for human use.

Because of its compact, stable design, SLIM could become a game-changer for treating chronic conditions like mental health, HIV prevention, or cancer with fewer doses and better adherence.

The SLIM system could redefine how we take medicine offering safer, longer-lasting, and more comfortable treatment through self-administered injections. It’s a promising leap toward better access and better outcomes, especially in global health.

Long-acting injectables are a proven way to boost adherence, especially for chronic conditions. But current systems are limited by: Large, painful needles, Viscous, hard-to-inject formulations and Poor suitability for self-administration.

SLIM overcomes these barriers with smart design: high drug loading, low viscosity, and small injection size all while delivering long-lasting effects.

Reference

Feig, V. R., Park, S., Rivano, P. G., et al. (2025). Self-aggregating long-acting injectable microcrystals. Nature Chemical Engineering, 2(3), 209–219. DOI: 10.1038/s44286-025-00194-x

Engineers develop a better way to deliver long-lasting drugs, MIT News, Massachusetts Institute of Technology, 24 March 2025

Owen A, Rannard S. Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy. Adv Drug Deliv Rev. 2016 Aug 1;103:144-156. Doi: 10.1016/j.addr.2016.02.003. Epub 2016 Feb 23. PMID: 26916628; PMCID: PMC4935562.

McEvoy, Joseph. (2006). Risks versus benefits of different types of long-acting injectable antipsychotics. The Journal of clinical psychiatry. 67 Suppl 5. 15-8.

National Research Council (US) Committee on Population. Contraception and Reproduction: Health Consequences for Women and Children in the Developing World. Washington (DC): National Academies Press (US); 1989. 4, Contraceptive Benefits and Risks.Available from: https://www.ncbi.nlm.nih.gov/books/NBK235069

Source of the Video: Giovanni Traverso (YouTube) _Self-Aggregating Long-Acting Injectable Microcystals

Disclaimer: The video is for educational and informational purposes only.

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Novel Oncolytic Virus Therapy Uses Transplant Rejection Pathway to Kill Cancer

May 10, 2025

by official.ajinkya11@gmail.com with No Comment Clinical Trails

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

Introduction

In a breakthrough that bring together virology, immunology, and genetic engineering, researcher from State Key laboratory of Targeting Oncology, China have developed a novel oncolytic therapy using a genetically modified Newcastle Disease Virus (NDV) that tricks the immune system into treating cancer cells as if they were foreign organ transplants. This approach, which uses the body’s natural “hyperacute rejection” mechanism typically seen in organ xenotransplants, showed notable results in early clinical trials for patients with advanced, treatment-resistant cancers.

Hyperacute rejection is a type of organ transport rejection that happens within minutes to hours after the transplant. It occurs when the recipient’s immune system already has antibodies that quickly recognize the new organ as foreign and attack it. This rapid immune response causes severe damage to the transplanted organ, often leading to its failure almost immediately.

Xenotransplant is a medical procedure where cells, tissues, or organs are transplanted from one species to another for example, transplanting a pig’s heart into a human.

The Innovation: NDV-GT and the aGal Trigger

The therapy uses a recombinant NDV that expresses the porcaine α1, 3-galactosyltransferase (a1, 3GT) gene, resulting in the presentation of αGal antigens on infected tumor cells. In humans, the αGal antigen is recognized as foreign due to the evolutionary loss of the α1, 3GT gene. Our immune systems naturally produce large amounts of anti-αGal antibodies, primarily from exposure to gut microbiota. This makes the immune system especially reactive to any cell displaying αGal.

By engineering NDV to express this foreign antigen on tumor cells, scientists effectively turned cancer cells into targets of a powerful immune cascade similar to organ rejection. This results in rapid tumor destruction through complement activation, thrombosis, and immune cell infiltration.

Preclinical Success in Monkeys

Using CRISPR-Cas9 technology, the researcher created a realistic liver cancer model in cynomolgus monkeys. The intravenous administration of NDV-GT in these monkeys led to remarkable tumor regression with many tumors disappearing entirely. The therapy not only lysed the cancer cells but also caused thrombotic blockage of tumor blood vessels mimicking hyperacute rejection seen in xenograft failures.

Immune profiling revealed activation of both innate and adaptive immune responses, including CD4+ and CD8+ T cell infiltration, increased expression of granzyme B and perforin, and reduced tumor angiogenesis markers. Importantly, no significant toxicity or organ damage was observed.

Clinical Trial Results

In a phase I interventional clinical trial (ChiCTR2000031980), 20 patients with various advanced, treatment-resistant cancers, including liver, lung, rectal, esophageal, breast, and cervical cancer and melanoma, were treated with intravenous NDV-GT. The results were prominent:

90% Disease Control Rate (DCR): 1 complete response, 6 partial responses, and 11 cases of stable disease.

No severe adverse events: Mild side effects, no cytokine release syndrome, and no detectable viral shedding.

Durable response: Severe patients experienced long-term stabilization o remission lasting up to 36 months.

One standout case involved a patient with advanced hepatocellular carcinoma and lung metastases. After 1.5 months of NDV-GT treatment, most tumors had disappeared, and serum tumor markers dropped significantly. Another patient with metastatic ovarian cancer achieved a partial remission for over a year.

Mechanism of Action

NDV-GT’s effectiveness lies in its dual mechanism :

Direct Oncolysis: NDV naturally prefers and destroys tumor cells while sparing healthy ones.

Immune Amplification: The engineered Gal expression triggers complement-mediated cytotoxicity and T-cell driven immune cascade, simulating a rapid rejection response that targets the tumor as a foreign organ.

This dual action also alleviated the immunosuppressive tumor microenvironment, making tumors more susceptible to further immune attack.

Safety and Implications

Despite the robust immune activation, NDV-GT treatment was well tolerated. No significant increase in neutralizing antibodies or adverse immunogenic effects was observed. The lack of toxicity and the specific targeting of tumor tissue underscore its promise for broader clinical use.

Conclusion

NDV-GT represents a groundbreaking shift in oncolytic virotherapy. Bby mimicking a hyperacute rejection response. This therapy turns the body’s natural defense mechanism against tumors in a way that is both powerful and safe. As phase II-III trials are being prepared, this immune- tricking virus could redefine treatment paradigms for refractory and metastatic cancers.

Reference

1. Liping Zhong, Lu Gan, Bing Wang et al, Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients, Cell, Volume 188, Issue 4P1119-1136.E23February 20, 2025.

2. Tricking the Immune System: A New Approach to Targeting Cancer Cells by Mimicking Pig Organs, Insight, 22 Jan 2025, available from https://oncodaily.com/insight/immune-system-229351

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Gold Nanoparticles Show Promise for Vision Restoration, Brown University Study Finds

May 8, 2025

by official.ajinkya11@gmail.com with No Comment Research

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

Researchers at Brown University have developed a groundbreaking vision restoration method that could help people regain vision loss due to retinal diseases like age-related macular degeneration (AMD) and retinitis pigmentosa. These common causes of vision loss damage the retina the light-sensitive layer at the back of the eye leading to progressive blindness. The innovative approach involves using gold nanoparticles, tiny biocompatible particles that can be safely introduced into the eye. When stimulated by near-infrared (NIR) laser light, these nanoparticles activate the remaining retinal cells, allowing them to send visual signals to the brain much like healthy photoreceptors do. This emerging technology has the potential to outperform existing retinal prosthetics by offering a minimally invasive, less painful alternative that could deliver higher-quality vision restoration. With its promise of improved outcomes, enhanced safety, and greater accessibility, this cutting-edge technique could transform the treatment of retinal degeneration and provide hope for millions living with severe vision impairment or blindness.

The Science behind the Innovation

In healthy eyes, specialized cells called photoreceptors rods and cones detect light and convert it into electrical signals. These signals are then passed to other key retinal cells, such as bipolar cells and ganglion cells, which relay the information to the brain, allowing us to perceive images. However, in degenerative eye diseases like age-related macular degeneration (AMD) and retinitis pigmentosa, these critical photoreceptors degenerate and eventually stop functioning, leading to progressive vision loss and, in severe cases, blindness. Remarkably, the inner retinal cells like bipolar and ganglion cells often remain intact and functional even after the photoreceptors are lost. Building on this insight, researchers at Brown University are developing an innovative vision restoration approach that bypasses the damaged photoreceptors entirely. By using advanced technology to directly stimulate the surviving inner retinal cells, this method could restore vision in individuals affected by retinal degeneration. This novel strategy has the potential to revolutionize vision loss treatment by targeting still-viable parts of the eye, offering a powerful alternative to traditional therapies and retinal implants.

Image Source: Brown University from an article: Golden eyes: How gold nanoparticles may one day help to restore people’s vision. Image Showing: How gold nanoparticles work and how it will create visual image in the mind of patient

The research team at Brown University has developed a cutting-edge technique involving the use of gold nanorods ultra-small, rod-shaped particles made of gold delivered directly into the eye through a minimally invasive procedure called intravitreal injection. These gold nanorods are precisely engineered to absorb near-infrared (NIR) light, a safe and effective wavelength that penetrates deep into the eye without causing damage, since it is minimally absorbed by water in the tissue. Once exposed to NIR light, the gold nanorods undergo a process called surface plasmon resonance, which generates localized and highly controlled heat. This subtle thermal energy can activate surrounding retinal nerve cells in two key ways: by inducing tiny electric currents across their membranes or by triggering specialized ion channels that respond to changes in temperature. This innovative approach offers a promising new method for restoring vision by reactivating the surviving retinal cells in individuals affected by degenerative eye diseases such as macular degeneration and retinitis pigmentosa. It also holds the potential to be a safer, more precise alternative to traditional retinal implants or surgical treatments.

Promising Results in Preclinical Studies

In experimental tests with mice suffering from retinal damage, the research team injected gold nanoparticles into the animals’ eyes and projected patterned near-infrared (NIR) laser light onto the retina. These light patterns, shaped like simple images, were designed to test whether the NIR light could stimulate the remaining healthy retinal cells. Using a powerful technique called calcium imaging; the scientists observed that the bipolar and ganglion cells key players in the visual signalling pathway responded to the laser patterns in a manner similar to how they would react to natural light in a healthy retina. Additionally, brain imaging revealed increased activity in the visual cortex, the region of the brain responsible for processing visual information. This indicated that the brain was once again receiving visual input, a strong sign that sight could potentially be restored. Even more promising, the gold nanoparticles remained stable and safely positioned within the eye for several months, with no signs of toxicity or inflammation. These results highlight the long-term potential of this non-invasive, laser-activated nanoparticle therapy as a safe and effective treatment for restoring vision in people affected by retinal degenerative diseases.

Advantages over Traditional Retinal Prosthetics

This new nanoparticle based method has several key benefits compared to current retinal prosthetic devices. First, it is minimally invasive unlike traditional devices that require complex surgery to implant electrodes; this approach only needs a simple injection into the eye, a common and low-risk procedure in eye care. Second, it offers much higher resolution. Existing devices are limited because they can only stimulate certain fixed spots in the retina, often resulting in blurry or narrow vision. In contrast, the nanoparticles can be targeted more precisely, even down to individual cells, and their stimulation pattern can be changed as needed, potentially restoring a full, detailed field of vision. Lastly, because it uses near-infrared (NIR) light, which doesn’t affect visible light, this method can work alongside any natural vision a person still has, making it a more flexible and user-friendly solution.

Future Outlook

Researchers aim to transform this groundbreaking vision restoration technology into a wearable device, such as smart glasses or high-tech goggles equipped with a camera and a near-infrared (NIR) laser system. The camera would continuously capture visual input from the surrounding environment, while the NIR laser projects precise light patterns onto the retina. These patterns would activate specially designed gold nanoparticles, allowing the user to perceive visual images without the need for invasive procedures. Although more research is needed to confirm long-term safety and effectiveness in larger animal models and eventually in humans, this innovative approach could revolutionize treatment options for millions suffering from retinal diseases and vision loss. By eliminating the need for genetic modification or complex surgical implants, this technology offers a potentially safer, more accessible and cost-effective alternative to current retinal prosthetics, paving the way for broader adoption and improved quality of life for patients worldwide.

Reference:

1. 1.Jiarui Nie, Kyungsik Eom, Hafithe M. AlGhosain, ntravitreally Injected Plasmonic Nanorods Activate Bipolar Cells with Patterned Near-Infrared Laser Projection ACS Nano 2025, 19, 12, 11823–11840, https://doi.org/10.1021/acsnano.4c14061

2. Golden eyes: How gold nanoparticles may one day help to restore people’s vision, 16 April 2025, Brown University.

3. Chen F , Si P , de la Zerda A , Jokerst JV , Myung D . Gold nanoparticles to enhance ophthalmic imaging. Biomater Sci. 2021 Jan 21;9(2):367-390. doi: 10.1039/d0bm01063d. Epub 2020 Oct 15. PMID: 33057463; PMCID: PMC8063223.

4. Natarajan S. Retinitis pigmentosa: a brief overview. Indian J Ophthalmol. 2011 Sep-Oct; 59(5):343-6. Doi: 10.4103/0301-4738.83608. PMID: 21836337; PMCID: PMC3159313.

5. Giuliana Gagliardi, Karim Ben M’Barek, Olivier Goureau, Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach, Progress in Retinal and Eye Research, Volume 71, 2019, Pages 1-25, https://doi.org/10.1016/j.preteyeres.2019.03.001

6. Treating retinal disease with tiny gold particles, 24 April 2025, Association of optometrist, available from https://www.aop.org.uk/ot/news/2025/04/24/treating-retinal-disease-with-tiny-gold-particles

7. NEI-funded researchers test new visual prosthesis system to restore vision, 18 April 2025, National Eye Institute, available from https://www.nei.nih.gov/about/news-and-events/news/nei-funded-researchers-test-new-visual-prosthesis-system-restore-vision

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

May 7, 2025

by official.ajinkya11@gmail.com with No Comment Clinical Trails

Medically Reviewed By Vikas Londhe, M.Pharm, Pharmacology

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?

May 6, 2025

by official.ajinkya11@gmail.com with No Comment Clinical Trails

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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

May 4, 2025

by official.ajinkya11@gmail.com with No Comment New Drug Approval

Medically Written and Reviewed By Pavan Reddy (Biomedical Engineer)

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

May 3, 2025

by official.ajinkya11@gmail.com with No Comment Research

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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

May 2, 2025

by official.ajinkya11@gmail.com with No Comment Research

Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)

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

April 29, 2025

by official.ajinkya11@gmail.com with No Comment Disease & Drugs Research

Written By: Lavanya Chavhan B.Pharm

Reviewed By: Vikas Londhe M.Pharm (Pharmacology)

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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