FRAXA Research Foundation is a rare disease foundation that is attempting to develop new treatments and ultimately a cure for Fragile X syndrome. FRAXA is a leader in what has recently been termed community-based drug development. Families and friends of people affected by Fragile X have come together, not only to advocate and raise awareness, but to specifically direct biomedical research toward therapeutic development.
Understanding and Tackling Fragile X Syndrome
Fragile X is the most common inherited cause of intellectual disability and autism spectrum disorders, and it is caused by a trinucleotide repeat expansion in a single gene. FRAXA's initial efforts have been directed toward funding basic research to understand the mechanisms of disease, then funding translational research to identify potential treatment targets. Success in these efforts forms the basis for ongoing community-based drug development programs, as we now have many “drug-able” targets, and we have identified therapeutics, such as specific drugs, which can address those targets. We have established highly effective and efficient methods for preclinical validation of promising therapeutic strategies. This key step that has led to many clinical trials in Fragile X patients.
Non-Profit Drug Discovery: A Model for Rare Disease Foundations
In many ways, these efforts resemble rational drug discovery as done by pharmaceutical companies, but FRAXA does this on a non-profit basis and on a shoestring budget. This method of community-based drug discovery has been adopted by numerous other rare disease foundations. However, many of these other organizations are quite young, with hundreds of new rare disease foundations launching in the last few years, many funded by groups such as the Chan Zuckerberg Initiative.
Since we have been at this for much longer than the average rare disease foundation, FRAXA has learned a great deal about the potential pitfalls involved in all these stages of the therapeutic discovery process and we are happy to share our experiences. It is always tempting to try to take shortcuts, and in consulting with many other rare disease foundations, we have observed a tendency to make the same mistakes over and over.
While community-based drug discovery may shorten the path to approval for new treatments, it still takes time. For example, it may be expensive and time-consuming to make multiple animal models and to characterize them thoroughly. Using patient-derived stem cells as a model system might seem like a quicker and easier approach. However, developing treatments for brain disorders requires live animals with whole brains, certainly for the testing of drugs prior to clinical trials, but also for a complete understanding of the disease process itself.
Leveraging Pharma and Biotech Partnerships in Drug Discovery
It is also critically important to develop relationships in the Pharma and biotech industry; many new rare disease foundations assume that the same academic labs which do basic and translational research on their disorder will be able to develop actual treatments for them. However, academics simply don’t understand the drug development process and industry partnerships are the only way to bring investigational therapies to the market. Industry partners also are the only ones who possess the expertise to obtain the financing required for proper testing of investigational therapeutics and for conducting the clinical trials themselves.
Of course, our community-based drug development efforts sometimes focus on repurposing available drugs, where formal FDA approval is not necessarily required. Here it is possible to work outside of industry partnerships, but more and more companies are springing up to exploit new methods for drug repurposing. Many of these companies are eager partners in the drug discovery and development process, bringing significant expertise and financing to the field.
The Power of Persistence in Community-Based Drug Development
Most of all, finding and testing new treatments for rare diseases requires persistence. Therapeutic development for brain diseases is especially difficult, and failures are quite common. It can be a daunting task, even for large Pharma companies with seemingly unlimited budgets.
So, community-based drug development, almost always done by small groups on a meager budget, certainly has its challenges. Many "shots on goal" are required for eventual success, but a sustained and thoughtful approach can succeed, and can make a real difference to rare disease patients and their families.
Dr. Michael Tranfaglia is Medical Director and Chief Scientific Officer of FRAXA Research Foundation, coordinating the Foundation’s research strategy and working with university and industry scientists to develop new therapeutic agents for Fragile X. He has a BA in Biology from Harvard University and an MD from the University of North Carolina at Chapel Hill. His son Andy has Fragile X syndrome.