Clinical Trials, CRISPR, and Big Data
FRAXA’s mission is to find effective treatments and ultimately a cure for fragile X by accelerating the pace of research. As in building a highway, we aim to speed the flow of traffic (research),eliminating bottlenecks along the route. Even the most complex processes have obvious choke-points that limit flow through the system. If these bottlenecks can be relieved, everything moves a lot faster.
We have been successful at speeding things up in this way.
Early Choke Points
In our early years, when little was known about the causes and effects of fragile X, we funded basic research. The field was the province of molecular biologists and geneticists, so we recruited neuroscientists. FRAXA’s booth each year at the enormous (30,000 scientists!) Society for Neuroscience conference, combined with FRAXA Investigators Meetings and Gordon Research Conferences, attracted new talent to the field. Fragile X is a hot topic in neuroscience today, and thousands of scientists around the world are tackling topics related to fragile X. Basic fragile X research is no longer a bottleneck, and so it is now a lower funding priority.
Other past bottlenecks, such as difficulties obtaining animal models and antibodies, have been resolved by targeted resource grants like the FRAXA Mutant Mouse Resource at Baylor College of Medicine, which distributes mice to scientists worldwide. These grants have ignited an explosion in translational research in fragile X, leading to many promising therapeutic strategies now being investigated.
The main choke point then moved further down the road to the preclinical studies. So FRAXA developed standardized methods to validate promising new drugs, with higher throughput and vastly greater efficiency, like the fragile X drug validation initiative (FRAXA-DVI) in Chile and Argentina.
On to Clinical Trials
With the preclinical bottleneck essentially resolved now, the current bottleneck is clinical trials.
In recent years, we’ve recruited and advised pharma industry partners who have invested tens of millions of dollars in fragile X clinical trials of investigational drugs (companies like Neuropharm, Novartis, Roche, Seaside, Alcobra, and Neuren.) This is one way to bring new fragile X treatments to market. But we also have a growing list of available drugs that have shown promise in preclinical testing, but are still waiting for clinical trials. Because these drugs are already on the market, few companies have any motivation to fund trials. While trials designed to obtain FDA approval for new drugs or new indications are very expensive, trials of available drugs in fragile X can be done on a smaller scale by clinical researchers for far less money. This is a great value, but the costs must be borne primarily by the fragile X community.
In 2016, FRAXA funded three clinical trials, in Quebec, Barcelona, and Antwerp. and two studies of biomarkers in people with Fragile X (in addition to several projects looking to identify biomarkers in animal models.)
In 2017-18 we launched FRAXA Clinical Trial Grants. From now on, all of our larger grants will be reserved exclusively for clinical research with fragile X subjects!
Available Drugs and Other Opportunities
At the same time, advances in technology have opened up new strategies. Drug repurposing is the application of approved drugs to treat new diseases. We have contracted with a leading company in this field, Healx, to conduct an in-depth study of biological changes caused by the fragile X mutation and match those changes to the known effects of all available drugs, via sophisticated computer algorithms. This big data match-making approach to drug repurposing has the potential to reveal treatments for fragile X that can be clinically useful right from the start.
We’re also funding efforts to fix fragile X at the most basic level, by reactivating the silenced FMR1 gene. FRAXA is funding groundbreaking studies using the latest technologies like CRISPR, Xi, and iDRiP to restore the function of the fragile X gene in boys and girls with the full mutation.
We’ve paved a lot of road, and sometimes it seems like our version of the Big Dig will never be done. But this is the last bottleneck. Successful clinical research gives us actual treatments for our kids, so we think it’s time to make this our top priority!
Dr. James Watson, winner of the Nobel Prize in Medicine and member of FRAXA’s scientific advisory board, wrote:
“Studies of fragile X have been galvanized by those most directly affected … experience shows that dedicated, resourceful, and, above all, motivated organizations like FRAXA sometimes do hold the key to cracking these diseases.” (DNA – The Secret of Life)