Letter from FRAXA’s Medical Director: State of the Science

On the eve of Thanksgiving, we want to thank everyone who has helped bring us so close to available treatments – and to take stock of where we are.

by Michael R. Tranfaglia, MD

Medical Director and Fragile X Parent

Each year, we’ve described ever greater progress toward our ultimate goal: disease-modifying treatments and an ultimate cure for Fragile X. At times it must seem that this quest will take forever; however, the pace of research has truly moved into high gear in 2011!

While FRAXA’s mission to find a cure for Fragile X is simple in concept, it is clearly a daunting task. To address the overwhelming complexity of this challenge, we have developed a plan of attack:

• We fund high-quality basic research on the causes of Fragile X, which leads to possible treatment strategies (therapeutic targets).

• We fund some of the finest neuroscientists in the world to pursue these leads and test potential therapeutics in animal models for Fragile X.

• All the while, we are developing close relationships with pharmaceutical companies that have drugs to address these therapeutic targets. These are drugs which may be of use for Fragile X, even though they may have originally been designed for other diseases (a strategy called re-purposing).

We are pleased to report that this strategy is working beautifully. Three major pharmaceutical companies (Novartis, Roche and Seaside Therapeutics) have successfully completed several phases of clinical trials of investigational new drugs for Fragile X, and their trials are now entering the final phase, which we hope will lead to marketing of these breakthrough treatments.

It now appears likely that a new class of medications called mGluR5 antagonists will be approved for the treatment of Fragile X in the next 2-3 years, although nothing is certain in the pharmaceutical business!

We encourage adults and children with Fragile X to consider joining the Phase 2 and Phase 3 clinical trials which are currently enrolling. More information on how to enroll is here

Even though we are very enthusiastic about mGluR5 antagonists, we are not putting all our eggs in one basket. We continue to test other treatment strategies and to look for more pharmaceutical partners to develop other drug classes for Fragile X. As a result, we now have a large pipeline of potential therapeutic compounds being tested, at multiple levels, in collaborations between FRAXA, university scientists and pharmaceutical companies worldwide. The success so far in developing mGluR5 antagonists has encouraged other companies to join in the hunt for new treatments for Fragile X, especially since this is now widely seen as the best way to develop new treatments for autism. A few years ago, we had to work very hard to make each new pharmaceutical company contact; now, many companies approach us, eager to get into this booming field.

As our understanding of the basic mechanisms of Fragile X has increased, we have also found a number of available medications which appear to possess disease-modifying properties. Earlier letters have mentioned the potential of lithium, minocycline and baclofen. This year, evidence was presented at the FRAXA Investigators Meeting that additional available drugs can reverse major symptoms in Fragile X mice. These results are still preliminary, but efforts are underway to organize clinical trials to test these strategies in Fragile X patients. Indeed, one can now envision rational combinations of available medications with even greater potential for disease-modifying effects; clinical trials utilizing such combinations are a near-term possibility.

We anticipate that many of these medications currently in development will be effective, disease-modifying treatments that will improve the lives of people with Fragile X and related autism spectrum disorders. Perhaps more importantly, this first generation of new treatments for Fragile X will pave the way for even better treatments to follow. At every stage, FRAXA will be there to spur and to speed the process of bringing innovative new treatments into the pipeline.

Thank you for all of your support.