A collaboration between startup company Healx and nonprofit FRAXA Research Foundation is moving forward with preclinical testing after identifying a list of existing therapies that hold the most promise for treating fragile X syndrome.
In late 2016, Healx, based at the University of Cambridge in England, received a $44,000 grant from FRAXA to identify new fragile X therapies based on treatments already approved by the U.S. Food and Drug Administration for other disorders, such as diabetes. This method, called drug repurposing, can be a quick and inexpensive way to develop new therapies.
To accomplish this, researchers used frontline drug-matching technologies developed at the University of Cambridge involving machine learning algorithms and computational biology to establish links between existing therapies and rare diseases.
This process identified eight therapies that hold the most potential for treating fragile x, including topiramate (anti-epileptic, autistic spectrum disorder), phenformin (linked to memory improvement), quercetin (antioxidant with anti-inflammatory proprieties), penbutolol (used to treat high blood pressure), zardaverine (a bronchodilator agent), disulfiram (used for chronic alcoholism), sulindac (non-steroidal anti-inflammatory) and metoprolol (beta-blocker used in autism treatment).
FRAXA has now granted Healx another $47,500 to continue with a new round of studies.
With the most promising compounds selected, the Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI), which provides quick, cost-effective, objective testing of potential fragile X treatments, is testing them in animal models of the disease at the University of Chile.
Researchers expect to finish the preclinical research within the next two years, after which they will determine which compounds are the best candidates to advance to clinical trials.
If any of the therapies show successful results in clinical trials, physicians can consider “off-label” prescription of the medicine or repurposing it to improve patients’ quality of life.
In a second study, Healx will investigate potential therapy combinations for the treatment of fragile x from a portfolio of both existing chemicals and natural products. Combining different compounds presents several therapeutic advantages, including a multi-pronged attack on the disease, lower doses due to synergistic effects, and reduced severe side effects.
Lead combination candidates identified through this study will be validated experimentally in cell systems and animal models in collaboration with FRAXA-DVI and other academic and industrial partners.