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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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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

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/

lariocidin

Scientists Discover Lariocidin, a Potent Lasso Shaped Antibiotic in Garden Soil

by with No Comment Disease & DrugsResearch

Written By: Lavanya Chavhan B.Pharm

Reviewed by Vikas Londhe M.Pharm (Pharmacology)

lariocidin

In a remarkable twist of scientific serendipity, researchers have discovered a powerful new antibiotic in an unexpected place a soil sample taken from a technician’s garden. The compound, named lariocidin, belongs to a rare class of antibiotics known as lasso peptides, and has shown promising results in combating drug-resistant bacteria.

A Backyard Breakthrough

Researchers from McMaster University in Ontario, Canada, and the University of Illinois, Chicago, led by Gerry Wright, worked together to discover lariocidin a compound shown to be effective against drug-resistant bacteria.

The discovery came during routine screening of soil samples for potential antimicrobial agents. One particular sample, taken from a home garden, yielded a previously unknown strain of bacteria that produced a unique antimicrobial compound. Upon further study, scientists isolated and characterized lariocidin, a small, intricately folded peptide that adopts a lasso-like structure.

Lasso peptides are named for their distinctive topology — a loop formed by the peptide backbone is threaded by its tail and locked into place, forming a mechanically constrained molecule. This unique structure often contributes to their stability and resistance to degradation, making them particularly appealing as drug candidates.

Lasso Peptide

A lasso peptide is a type of ribosomally synthesized and post-translationally modified peptide (RiPP) that has a unique and highly stable three-dimensional structure, resembling a lasso or slipknot.

Lasso peptides are characterized by A macrolactam ring (a circular peptide structure) at the N-terminus. A tail segment that threads through this ring during synthesis. The tail is “locked” in place by bulky amino acid residues or disulfide bonds, preventing it from slipping back out much like a rope threaded through a loop and pulled tight, hence the name lasso.

This structure is thermodynamically stable and resistant to heat, enzymatic degradation, and extreme pH conditions.

Targeting the Ribosome: A Novel Mechanism

What sets lariocidin apart is its mechanism of action. Unlike many antibiotics that attack bacterial cell walls or DNA replication, lariocidin targets bacterial ribosomes the machinery responsible for protein synthesis. It binds tightly to the ribosome and disrupts translation, halting the production of essential proteins needed for bacterial survival and replication.

Structural studies revealed that lariocidin latches onto a previously underexplored site on the ribosome, a feature that likely contributes to its efficacy against multi-drug resistant strains. This includes pathogens such as Staphylococcus aureus, Enterococcus faecium, and certain strains of Pseudomonas aeruginosa, which have become increasingly difficult to treat with conventional antibiotics.

A Weapon against Superbugs

The rise of antibiotic resistance is a global public health crisis. Each year, antimicrobial-resistant infections claim hundreds of thousands of lives worldwide. The emergence of lariocidin offers a glimmer of hope, especially since it belongs to a relatively untapped class of natural antibiotics with novel mechanisms of action.

Early laboratory studies have demonstrated that lariocidin is not only potent but also exhibits low toxicity to human cells, an essential step toward potential clinical development. Researchers are now working to synthesize analogs of lariocidin, optimize its pharmacokinetics, and assess its efficacy in animal models of infection.

Current status of Lariocidin

In preclinical testing, lariocidin showed strong antibacterial effects without exhibiting toxicity to human cells. In mouse models infected with A. baumannii, the antibiotic significantly lowered bacterial levels and improved survival outcomes.

At present, scientists are working to optimize lariocidin’s potency and are developing scalable production methods to support future clinical use. Although the results so far are encouraging, additional research and clinical trials are essential to confirm its safety and effectiveness in humans.

Nature Still Has Secrets to Reveal

The story of lariocidin is a potent reminder that nature, even in the soil of a backyard garden remains a vast and largely unexplored resource for life-saving compounds. With rising antibiotic resistance threatening global health, the discovery underscores the importance of continued investment in natural product research and microbial biodiversity.

If further studies validate its safety and effectiveness, lariocidin could represent the first in a new class of antibiotics, one that might help turn the tide against resistant bacterial infections.

References

1.Jangra, M., Travin, D.Y., Aleksandrova, E.V. et al.A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome. Nature(2025). https://doi.org/10.1038/s41586-025-08723-7

2. New lasso-shaped antibiotic kills drug-resistant bacteria, Nature Podcast, Nature, 26 March 2025

3. Julian D. Hegemann, Marcel Zimmermann, Xiulan Xie et al, Lasso Peptides: An Intriguing Class of Bacterial Natural Products, Accounts of Chemical ResearchVol 48, Issue 7 2015

4. Cheng Cheng, Zi-Chun Hua et al, Lasso Peptides: Heterologous Production and Potential Medical Application, Front. Bioeng. Biotechnol. Volume 8 – 2020 https://doi.org/10.3389/fbioe.2020.571165

5. Digging in the dirt: Scientists discover a new antibiotic compound from an old source, University of Minnesota, 31 March 2025

6.Molecule Discovered In Backyard Soil Can Fight Drug Resistant Bacteria, Technology Networks Immunology and Microbiology, 28 March 2025

 

epv

Earth Day Spotlight: How Ecopharmacovigilance Protects the Planet from Pharmaceutical Pollution

by with No Comment Disease & DrugsResearch

Medically Written and Reviewed by Vikas Londhe M.Pharm (Pharmacology)

epv

As we honour Earth Day and reflect on our collective duty to protect the environment, a lesser-known but critical issue deserves the spotlight: Ecopharmacovigilance. In the era where much attention is given to industrial emissions and plastic waste, Very few people are aware of the silent threat created by pharmaceuticals entering the ecosystems. That’s where ecopharmacovigilance comes in

What is Ecopharmacovigilance?

Pharmaceuticals are meant to be developed for the consumption of humans; however, once humans consume pharmaceuticals, the by-products or remains are excreted into the environment in different ways, and once they enter the environment, they start polluting nature and harming the aquatic animals and other species, including soil and trees. Hence, where pharmacovigilance is the detection and understanding of the side effects of pharmaceuticals on humans, ecopharmacovigilance refers to the science and activities related to the detection, evaluation, understanding, and prevention of adverse effects or other problems related to the presence of pharmaceuticals in the environment. On a broader scale, it is monitoring the presence of pharmaceuticals in the environment, assessing the impact on non-target organisms, understanding it thoroughly, and developing the preventive strategies in a way that any harm to nature due to the presence of pharmaceuticals in the environment should be avoided timely and appropriately.

According to the World Health Organization, treated sewage water, surface water, drinking water, groundwater, sediment, soil, and biota contain hundreds of pharmaceuticals. Increasing use of drugs worldwide, and some of them are resistant to degradation, are the main reasons behind their presence in harmful quantities in nature. The most notable pathways of these pharmaceuticals are excretion of used drugs, drug manufacturing, industrial and home wastewater, aquaculture, manure application, landfills, and incineration.

Why Should We Care?

While pharmaceuticals are essential for human and animal health, their unintended environmental footprint is becoming increasingly evident. Studies have shown:

Increasing Antibiotic Resistance: Antibiotic resistance, or antimicrobial resistance (AMR), poses a global threat due to the irrational use of antibiotics; however, the presence of antibiotics in the environment makes the condition worse, as the exposed antibiotics in open environments make bacterial infections hard to treat. AMR caused an estimated 1.27 million deaths globally in 2019.

Effect on aquatic life: As most of the drugs end up in aquatic bodies like rivers, streams, ponds, and oceans through pathways mentioned above, they are not designed to be there or show a positive effect on wildlife present in waters. They show a negative effect on aquatic animals like fish and affect their ability to reproduce, cause behavior changes, or have direct toxic effects. Hormonal drugs, like estrogens from contraceptives, are supposed to be causing these types of effects. Some reports show that male fish were feminized by ethinyl estradiol and frogs were killed by contraceptive tablets. Psychiatric and cardiovascular drugs have been linked to altered behavior and physiological changes in aquatic animals. Some reports related to it show that aggression is caused in lobsters due to antidepressants and spawning in shellfish by fluoxetine.

Current Status of Ecopharmacovigilance

Regulatory Recognition

The OECD report Pharmaceutical Residues in Freshwater: Hazards and Policy Responses highlights the growing concern over pharmaceutical contamination in global freshwater systems due to human and veterinary use, manufacturing, and improper disposal.

The report emphasizes the need for a life cycle, multi-sectoral approach involving source-directed, use-oriented, and end-of-pipe solutions. This includes better monitoring, green pharmaceutical design, responsible prescription and use, proper disposal systems, and advanced wastewater treatment.

International Cooperation Needed: The report also emphasizes the importance of data sharing, international standards, public education, and financial strategies to implement sustainable pharmaceutical pollution control.

EMA and FDA integrated environmental risk assessments (ERAs) into the drug approval process

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have taken significant steps to integrate Environmental Risk Assessments (ERAs) into the drug approval process, marking a growing recognition of the environmental impact of pharmaceuticals.

Environmental risk assessments evaluate the potential environmental impact of a pharmaceutical substance once it enters ecosystems, typically through human excretion, improper disposal, or manufacturing waste. These assessments analyze factors such as persistence in the environment, bioaccumulation in wildlife, toxicity to aquatic and terrestrial organisms, and potential for environmental transformation into harmful by-products.

Since 2005, the EMA has required ERAs for all new marketing authorization applications in the EU.

The FDA has also implemented environmental reviews under the National Environmental Policy Act (NEPA). For human drugs, applicants typically submit an Environmental Assessment (EA) or a claim for categorical exclusion, depending on the drug’s characteristics. The FDA assesses factors such as expected introduction into the environment, manufacturing and disposal practices, and the cumulative impact of widespread use.

As awareness of pharmaceutical pollution grows, both agencies are expected to tighten guidelines, enhance transparency, and collaborate internationally on standardized ERA methodologies. This reflects a shift toward sustainable drug development that balances therapeutic benefit with environmental responsibility.

What Can You Do?

On Earth Day and every day individuals can play a role in supporting ecopharmacovigilance:

Proper Medication Disposal

Don’t flush unused meds in the toilet or sink.

Use take-back programs: Many pharmacies and communities have medication disposal programs.

If no programs are available, follow the FDA’s or local authority’s guidelines for trash disposal (e.g., mix with unpalatable substances like coffee grounds or cat litter, then seal in a bag).

Buy Only What You Need

Avoid stockpiling medications. It reduces waste and environmental load from expired drugs.

Use Medications Responsibly

Follow prescriptions exactly—using less or more than necessary not only harms health but also leads to excess drugs in the environment.

Spread Awareness

Talk to friends and family about why proper disposal matters

Share posts or articles about EPV and pharmaceutical pollution.

Ask Your Pharmacist

If unsure about disposal or environmentally safer alternatives, ask to your pharmacist. Pharmacist is the healthcare provider who is easily accessible compare to other HCPs. Added to it possesses good knowledge about medicine use and disposal. So some may offer eco-friendly info or take-back services.

Support Green Pharmacies

Support pharmacies and drug companies who are committed to reducing environmental impact (e.g., sustainable packaging, greener drug production).

Advocate for Change

Encourage local governments and health organizations to implement and promote better environmental drug policies.

Avoid Unnecessary Use of Over-the-Counter Drugs

Many people take OTC drugs like painkillers or antacids unnecessarily. This leads to increased production, use, and environmental excretion.

Looking Ahead

Ecopharmacovigilance is still evolving, but it’s becoming an essential part of environmental health strategies. With collaborative efforts from the healthcare industry, regulators, and the public, we can reduce the ecological footprint of lifesaving medicines.

References:

1. Ecopharmacovigilance: Ensuring Environmental Safety from Pharmaceuticals, Uppsala Reports, 15 Oct 2024, available form https://uppsalareports.org/articles/ecopharmacovigilance-ensuring-environmental-safety-from-pharmaceuticals/

2. The Impact of Pharmaceuticals Released to the Environment, United state environmental Protection Agency.

3. Dutta A, Banerjee A, Chaudhry S. Ecopharmacovigilance: Need of the hour. Indian J Pharm Pharmacol 2022;9(2):77-80.

4. Eapen JV, Thomas S, Antony S, George P, Antony J. A review of the effects of pharmaceutical pollutants on humans and aquatic ecosystem. Explor Drug Sci. 2024; 2:484–507. https://doi.org/10.37349/eds.2024.00058

5. OECD (2019), Pharmaceutical Residues in Freshwater: Hazards and Policy Responses, OECD Studies on Water, OECD Publishing, Paris, https://doi.org/10.1787/c936f42d-en

6. Paut Kusturica M, Jevtic M and Ristovski JT (2022), minimizing the environmental impact of unused pharmaceuticals: Review focused on prevention. Front. Environ. Sci. 10:1077974. Doi: 10.3389/fenvs.2022.1077974

7. Guideline on the environmental risk assessment of medicinal products for human use, Committee for Medicinal Products for Human Use (CHMP), European Medicine Agency.

8. Environmental Impact Review at CDER, 07 Jan 2025, US Food and Drug Administration, available fromhttps://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/environmental-impact-review-cder

MS

Could High-Dose Vitamin D Help Fight Early Multiple Sclerosis? New Evidence Says Yes

by with No Comment Disease & DrugsResearch

Written and Reviewed by Vikas Londhe M.Pharm (Pharmacology)

MS

A recent study published in JAMA on March 10, 2025, titled “High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial,” investigated the efficacy of high-dose cholecalciferol (vitamin D) as a monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). This randomized clinical trial enrolled participants diagnosed with CIS, a condition characterized by a single episode of neurological symptoms indicative of MS. The objective was to determine whether high-dose vitamin D supplementation could delay or prevent the progression from CIS to clinically definite MS.​ The trial’s results indicated that participants receiving high-dose vitamin D exhibited a significant reduction in disease activity compared to those in the placebo group. Specifically, MRI scans revealed fewer new or enlarging lesions in the vitamin D group, suggesting a potential neuroprotective effect of high-dose cholecalciferol in the early stages of MS.

Link between Vitamin D and MS

Multiple sclerosis (MS) is a long-term disease that affects the central nervous system by damaging the protective covering of nerves (myelin). This damage disrupts nerve signals, causing symptoms that vary from mild fatigue to severe paralysis and cognitive issues. The exact cause is unknown, but it likely involves both genetics and environmental factors. MS affects over 2.8 million people worldwide and is a major cause of disability in young adults.

Vitamin D is a fat-soluble vitamin that is important for strong bones and maintaining calcium levels in the body. It also plays a role in regulating the immune system. Vitamin D works by interacting with a specific receptor Vitamin D receptor (VDR) found in many immune cells. Research suggests that it can affect the immune system by reducing the growth of certain T cells, supporting regulatory T cells, and influencing the production of inflammatory substances like cytokines. Because of these effects, scientists are interested in studying whether vitamin D supplements could help manage multiple sclerosis (MS), a disease linked to immune system dysfunction.

The D-Lay MS Trial (NCT01817166): The D-Lay MS trial was a rigorous, double-blind, placebo-controlled study conducted across 36 MS centers in France. Recruitment spanned from July 2013 to December 2020, with final follow-ups completed in January 2023. The study aimed to determine whether high-dose cholecalciferol (vitamin D3) could reduce disease activity in individuals diagnosed with CIS or early-stage relapsing-remitting MS (RRMS).

A total of 316 patients aged 18–55 years, diagnosed with CIS within the previous 90 days, were enrolled. Inclusion criteria required a serum vitamin D concentration below 100 nmol/L and MRI findings consistent with the 2010 MS diagnostic criteria. Notably, participants had not received any prior disease-modifying treatments.

Intervention and Study Groups: Participants were randomly assigned to one of two groups:

High-dose cholecalciferol (100,000 IU) every two weeks (n = 163)

Placebo group receiving a matching supplement (n = 153)

The intervention period lasted 24 months, during which disease activity and clinical outcomes were closely monitored.

Key Outcomes and Findings The primary endpoint of the study was disease activity, defined as the occurrence of relapses and/or MRI activity (new or contrast-enhancing lesions). Secondary outcomes included MRI-based disease activity measures, clinical relapses, and safety assessments.

Primary Outcome Results

60.3% of patients in the vitamin D group experienced disease activity, compared to 74.1% in the placebo group. The time to disease activity was significantly longer in the vitamin D group (432 days) compared to the placebo group (224 days).

MRI-Based Findings: Patients in the vitamin D group demonstrated significant reductions in MRI-based disease activity: MRI activity: 57.1% in the vitamin D group vs. 65.3% in the placebo group.

New lesion occurrence: 46.2% in the vitamin D group vs. 59.2% in the placebo group.

Contrast-enhancing lesions: 18.6% in the vitamin D group vs. 34.0% in the placebo group.

Clinical Outcomes and Safety While MRI-based improvements were evident, no significant differences in relapse rates were observed:

17.9% of patients in the vitamin D group experienced relapses vs. 21.8% in the placebo group

Regarding safety, severe adverse events were reported in 17 patients in the vitamin D group and 13 patients in the placebo group. However, none of the adverse events were directly attributed to vitamin D supplementation.

Interpretation and Clinical Implications

This study provides strong evidence that high-dose vitamin D can reduce MRI-based disease activity in CIS and early MS. These findings suggest potential neuroprotective and immunomodulatory effects, possibly delaying progression to clinically definite MS. However, the lack of significant impact on relapse rates indicates that vitamin D supplementation may not be a stand-alone treatment but could serve as an adjunct to existing disease-modifying therapies.

Conclusion and Future Directions

The D-Lay MS trial highlights the benefits of high-dose vitamin D (100,000 IU biweekly) in reducing MRI-based disease activity. Although it did not significantly impact relapse rates, the delayed onset of disease activity suggests its potential as an early intervention strategy. Further research is needed to optimize dosing, assess long-term safety, and evaluate the role of vitamin D in combination with other MS treatments.

References

  1. Feige J, Moser T, Bieler L, et al, Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats. Nutrients. 2020 Mar 16;12(3):783. Doi: 10.3390/nu12030783. PMID: 32188044; PMCID: PMC7146466.
  2. Aderinto, N., Olatunji, G., Kokori, E. et al.High-dose vitamin D supplementation in multiple sclerosis: a systematic review of clinical effects and future directions. Discov Med1, 12 (2024). https://doi.org/10.1007/s44337-024-00023-9
  3. Thouvenot E, Laplaud D, Lebrun-Frenay C, et al. High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial. JAMA.Published online March 10, 2025. doi:10.1001/jama.2025.1604

4. Sintzel, M.B., Rametta, M. & Reder, A.T. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther 7, 59–85 (2018). https://doi.org/10.1007/s40120-017-0086-4