While genetic therapy has the potential to be transformative for Prader-Willi syndrome, the fact is genetic therapy technology is still in its early stages and it could be many years before it’s viable for PWS. While FPWR continues to move genetic approaches forward, we are cognizant of the need for treatments to be available in the short-term. As such, we have developed a strategy and research plan that balances short-term goals to repurpose existing therapies that may improve health and quality of life, with the longer-term goals of developing new and potentially transformative therapeutics.Two research programs: the clinical care research program and the pharmacotherapies program, have been established to accelerate development of pharmacological treatments for PWS patients. The goal of the clinical care research program is to address the most immediate challenges of PWS and improve the quality of life of patients, whereas the pharmacotherapies program will focus on the development of new and potentially transformative treatments for PWS.
Both the Clinical Care and Pharmacotherapies programs aim to reduce the huge investment of time and money that developing a drug from scratch requires. The average time for a drug to go through pre-clinical and clinical research and receive approval is 12-15 years, and the process can end up costing millions of dollars. To accelerate the availability of treatments for PWS, our programs will use a drug/device repurposing strategy. This approach refers to the process of using existing drugs/devices to treat an indication different than what they were originally developed for. This strategy can quickly advance therapies as it builds upon data that is already available.
The existing drugs/devices could include approved and marketed drugs, pre-clinical molecules from academic institutions that were never advanced, compounds already in clinical development for other indications, or drugs/devices that failed to show efficacy in clinical trials for the indication being studied but have the potential to be used for other diseases. A great example of this approach is the development of sildenafil (Viagra), which was originally tested for the treatment of angina without much success. A serendipitous discovery of its side-effects in clinical trials led to it being repurposed for the treatment of erectile dysfunction instead.
Clinical Care Research Program: Repurposing FDA Approved Drugs to Speed Up Treatment Availability
The clinical care research program will take a directed approach to evaluating drugs/devices that are already approved and on the market for the treatment of other conditions, and support repurposing of the most promising ones for PWS. This can significantly reduce the time and expense required to get the therapy approved for use in PWS as data regarding its safety and efficacy are already available, a process that, as mentioned above, can take several years. This effort will focus on symptoms that are of immediate concern to the PWS community. The clinical care research program will be guided by the clinical care advisory board, which is a collaborative panel of physicians, health professionals, and parents.
With the help of this panel, we will identify studies and trials, with a relatively short turn around time, and high feasibility, to address symptoms that are most challenging to individuals with PWS and their caregivers. Some of the symptoms under consideration include behavioral problems, scoliosis, seizures, GI motility, central adrenal insufficiency, hypotonia, etc. Following this, the FPWR team will investigate currently available treatments for each symptom and begin to develop comparative studies to evaluate whether these treatments could be more efficacious in improving PWS symptoms than those currently being used by patients. The goal is to develop studies that are highly feasible and can be rapidly repurposed for PWS within a short time frame (1-3 years).
The Pharmacotherapies Program: Supporting Potential Therapies in Early Stage Development
The pharmacotherapies program aims to develop new pharmacological agents for PWS using a three-pronged approach, with an initial focus on obesity and hyperphagia.
The first approach is directed towards discovering new drugs using a high-throughput screening strategy which requires the development of cellular models for PWS. The second approach focuses on drugs that are currently being developed by industry for obesity and hyperphagia. Although this strategy is conceptually similar to the one used for the clinical care program, a key difference is that this program will focus on early-stage therapies, such as those that are in pre-clinical or clinical development but not already marketed. The aim of this program is not to perform or fund clinical trials for PWS but to support additional studies or encourage the development of clinical trials in PWS by industry.
The third approach is to promote and support pharmaceutical companies that are already developing drugs for PWS. Some clinical trials for existing or altered drugs are already either ongoing or planned in PWS, and supported by FPWR. An example of this is a Phase 1 clinical study, co-funded by FPWR, to investigate Diazoxide Choline Controlled Release (DCCR) tablets, a new formulation of the FDA-approved drug, Diazoxide, for treatment in PWS.
FPWR prioritizes innovative research that will eliminate the challenges of Prader-Willi syndrome. The clinical care and pharmacotherapies programs balance our short-term goals of improved quality of life with our long-term goals of transformative treatments. Together with our translational research programs, grants program and research tools, we will address the challenges of therapeutic development and accelerate the availability of treatments for PWS.