FRAXA Research Foundation initially partnered with Healx in 2016 to identify existing drugs with potential to treat fragile X syndrome, using machine learning algorithms and computational biology. The study produced results, and now FRAXA and Healx have launched a new round of studies to evaluate combinations of compounds, including both drugs and natural products.
The purpose of this NeuroNEXT study is to find out if the drug AFQ056, made by the pharmaceutical company Novartis, is safe and has beneficial effects on language learning in children who have fragile X syndrome (FXS). The study also aims to find out if a structured language intervention can help children with fragile X syndrome communicate better.
“We are trying to target the first event that goes wrong in fragile X syndrome”, says Todd, “One reason our previous attempts to develop treatments for fragile X syndrome have failed is that they’ve tried to target the downstream effects of losing the fragile X protein. The protein does many things… bypassing all the functions that it normally takes care of has proven difficult from a pharmacologic perspective.”
While there are over 8,000 rare diseases affecting an estimated 350 million people worldwide, only around 200 of these conditions have effective treatments. Due to the high cost of developing new drugs, rare diseases have historically been less attractive to pharmaceutical companies. Drug repurposing systematically leverages the detailed information available on approved drugs and reduces the time and money needed to deliver safe “new” treatments, but with greater success rates and a potentially more immediate impact on health care.
With a 2017 grant from FRAXA Research Foundation of $90,000, Dr. Andreas Frick’s team at Neurocentre Magendie, in France, will test non-invasive imaging using magnetic resonance imaging (MRI) as a potential biomarker for future fragile X syndrome clinical trials.
According to Dr. Erickson, AZD7325 is a drug that selectively boosts GABA neurotransmission in the brain. GABA is the primary neurochemical in the brain that blocks brain activation. GABA activity is in balance in the brain with Glutamate activity, which is the primary neurochemical that causes brain activation. In fragile X, GABA activity is insufficient and glutamate activity is excessive, likely causing brain activity to be out of balance. AZD7325 attempts to correct parts of this imbalance by boosting the insufficient GABA activity in the brains of people with fragile X
With a $51,000 grant from FRAXA Research Foundation, Dr. Craig Erickson will conduct a double-blind, placebo-controlled clinical trial of AZD7325 in adults with fragile X syndrome at Cincinnati Children’s Hospital. The compound being studied is an investigational new drug from AstraZeneca that targets GABA (A) receptors.
With a $66,714 grant from the FRAXA Research Foundation awarded over 2015-2017, Dr. Francois Corbin at the Universite of Sherbrooke will test the safety and synergistic effects of lovastatin and minocycline in patients with fragile X syndrome.
With a $90,000 grant from FRAXA Research Foundation awarded over 2016-2017, University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, are exploring drug combinations to limit hypersensitivity to sounds in fragile X mice.
Drs. Mahmoud Pouladi and Kagistia Utami at the Agency for Science, Technology and Research (A*STAR) in Singapore have won a $67,500 research grant from FRAXA Research Foundation. Their goal is to reactivate the gene which is silenced in people who have fragile X syndrome.
The FRAXA Drug Validation Initiative (FRAX-DVI) provides speedy, cost-effective, objective testing of potential new fragile X treatments. FRAXA has funded FRAX-DVI for $50,000 in 2017.
This 2017 grant of $90,000 is funded jointly by FRAXA and the Fragile X Research Foundation of Canada. A previous FRAXA grant to the Sonenberg lab has led to great interest in the available drug, metformin, as a potential treatment for fragile X syndrome. FRAXA is currently organizing clinical trials of metformin.