Breaking the mouse barrier – A mouse isn’t a human, but most human therapies are tested in rodents. This helps to explain why more than 90% of new cancer and other drugs fail. Why is this happening and what’s being done about it?
The high failure rate of new drugs is driving astronomical drug costs. Drug companies have to charge outrageous prices for the few drugs that do succeed in order to make up costs for the many that don’t.
Researchers have known for years why rodent testing doesn’t translate well to humans.
- Lab rodents are raised in more sterile environments. They’re not normally exposed to the thousands of factors that humans encounter in their daily lives. So, when a drug is tested on lab mice, it’s not in a real-life environment.
- Rodents are highly resistant to many toxins and human diseases, so researchers often have to artificially provoke a disease through genetic manipulation or injuring the mouse to create the condition. It’s not real life and it’s not pleasant for the mouse.
- It’s expensive to raise rodents into old age, i.e., a few years, so most experiments are done on animals that are a few weeks or months old. For many cancers that develop over the years and for diseases of aging, such as cardiovascular disease, this doesn’t translate well.
- Older human patients often have multiple medical conditions. Inducing multiple conditions in lab animals is too expensive and time-consuming and usually isn’t done, so it doesn’t reflect the real world.
- Lab rats aren’t given the chance to live holistic lifestyles to prevent these diseases in the first place.
Due to all of that, many drugs fail after they reach the expensive clinical trial stage, where doctors discover that the drug doesn’t behave in the same way it did in a mouse. At this point, investors have usually spent hundreds of millions of dollars or more.
Despite the high failure rate and costs, regulatory agencies insist on using rodent models. The rationale is that a bad system is better than no system at all. But the costs for many patients and the system have become so great that unaffordable drugs are often just as bad as no drugs at all. Worse yet, less expensive generic drugs that often work just as well are sometimes shoved aside in the interests of higher revenues from new drugs.
What’s the solution?
The answer is a more holistic approach – no surprise for readers of Best Holistic Life magazine. Artificial intelligence and nutraceuticals are leading the way.
AI is revolutionizing the pharmaceutical development industry, and it’s accompanied by a growing emphasis on nutraceuticals as alternatives to synthetic drugs.
Machine learning algorithms can analyze vast amounts of biological data to identify promising drug candidates and predict how well and safely they work. This computational approach helps researchers prioritize the most promising candidates before moving to animal or human studies. The use of AI extends to clinical trials, where it can improve patient recruitment, data collection, and analysis. AI-based technologies can quickly analyze vast databases of chemical compounds, predict toxicity and side effects, and provide real-time insights during trials. This leads to better-designed and safer clinical trials, improved patient outcomes, and lower costs.
Accounting for multiple disease conditions in older patients is another crucial aspect. Researchers are developing more sophisticated preclinical models and clinical trial designs that account for those. AI is being leveraged to analyze real-world data and electronic health records to identify patterns in patient populations with multiple conditions, helping researchers design more targeted clinical trials and drugs that are effective across a broader range of patient profiles.
Advanced in vitro models (i.e., experiments outside humans or other animals) like organoids (mini-organs) and organs-on-chips are being combined with AI-driven analysis to create more predictive systems for drug testing. These models can be customized to represent specific patient populations or disease states, more accurately representing human physiology than rodent models.
There has been a rapid increase in clinical trials using nutraceuticals instead of synthetic drugs. This shift reflects a growing interest in natural, food-derived compounds that may have therapeutic benefits with potentially fewer side effects than traditional pharmaceuticals. AI is also being applied to nutraceutical research, helping to identify promising compounds from natural sources and predict their potential health benefits.
Companion animals are emerging as valuable models in drug development. Dogs naturally develop many of the same diseases as humans and share similar genetic and physiological characteristics. Studying naturally occurring diseases in companion animals can provide more relevant data than induced conditions in lab rats, offering a more human-relevant and humane context for drug development. (Hint – the first longevity therapy was recently given conditional FDA approval for dogs before humans).
The integration of AI, companion animals, in vitro models, and nutraceuticals is creating a more holistic and predictive drug development pipeline. This multifaceted strategy aims to improve the translation of preclinical findings to human outcomes. To learn more, just ask any AI chatbot to give you the leading websites on AI in cancer therapy.
References
Marshall, Lindsay J., et al. “Poor translatability of biomedical research using animals—A narrative review.” Alternatives to Laboratory Animals 51.2 (2023): 102-135. Hamilton, Sean, and Benjamin R. Kingston. “Applying artificial intelligence and computational modeling to nanomedicine.” Current Opinion in Biotechnology 85 (2024): 103043. Alonso-Roman, Raquel, et al. “Organ-on-chip models for infectious disease research.” Nature Microbiology 9.4 (2024): 891-904. Medrano, Madeline, and L. F. Carver. “The Integration of Community-Dwelling Non-Human Companion Animals in Research Programs: A Scoping Review.” One Health Innovation 2.1 (2024). Newell, Jonathan, et al. “Clinical Application and Trials with Nutraceuticals.” Nutraceuticals for Alzheimer’s Disease: A Promising Therapeutic Approach. Singapore: Springer Nature Singapore, 2023. 287-317
- About the author: Douglas Mulhall’s latest book, Discovering the Nature of Longevity: Restoring the Heart and Body by Targeting Hidden Stress, explores prevention and therapies for heavy metals contamination. The American Institute of Stress recommends it and carries a Foreword by the Chief author of the American Heart Association statement on toxic heavy metals. He co-develops award-winning certifications and standards for products globally and is a registered ISO expert on a global standard for declaring the contents of products.
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