How Close are We to a Cure for Fragile X?

Jeannie Lee

I would say to families, not to lose hope because I think we are in a position now to make a real difference to the lives of patients and the lives of families.

Jeannie Lee, MD, PhD
FRAXA Investigator
Harvard Medical School
Massachusetts General Hospital

What will a cure for Fragile X look like? It’s a question we all ask at some point. Will it be a pill taken every day for life? Will it be combinations of medicines, tailored to each individual? Will it be a protein replacement injection once a week? Will it be a one-time gene therapy infusion that fixes every cell in the body at the same instant?

The answer is probably all of the above. The cure for Fragile X isn’t a pipe dream. It’s a process, and we are right in the thick of it.

Engineering a Cure for Fragile X

What FRAXA does goes far beyond what most people think of as “research.” We are running a massive engineering project. We are constantly troubleshooting this complex project and making adjustments. Although this is a daunting task, we have validated dozens of potential therapeutic strategies which are now ready for clinical trials. Indeed, that’s where the backlog is today: we have far more treatment candidates than we have clinical trial capacity.

The Fragile X field has had challenges with clinical trials (as is true for all fields of brain research), and so we are developing new methods and measures to assess treatments quickly and efficiently, using fewer subjects. For example, because of donors like you, at this very moment at Boston Children’s Hospital, FRAXA Investigator Dr. Carol Wilkinson is evaluating a child’s thinking, skills, and communication by measuring brain activity with non-invasive electroencephalography (EEG), instead of relying on subjective interviews.

It looks increasingly likely that combinations of conventional drugs will be required to obtain useful therapeutic effects in Fragile X. As we have learned more about the functions of the missing protein (FMRP), we have found that it does so many different things in the brain that it is unrealistic to expect any one small molecule to fix everything.

Because of donors like you, at this very moment in Cambridge, England, supercomputers at Healx are harnessing Artificial Intelligence (AI) techniques to data-crunch millions of combinations of medicines and supplements available today at your local drug store. In Santiago, Chile, Dr. Patricia Cogram and her team at the FRAXA Drug Validation Initiative (DVI) are testing the best combinations (from that long list of validated candidates!) in mice, using new methods to detect truly synergistic effects. We’ve had some definite hits, and now we are planning clinical trials of the best combinations, using the most advanced trial methods.

This project was made possible by $80,000 in contract research grants from FRAXA to Healx, which led to $56 Million in additional private financing, enabling Healx to dramatically expand this project and fund clinical trials.

At the same time, we are pursuing definitive treatment for Fragile X [a cure]. We are funding major projects studying gene therapy, gene repair, gene reactivation, and protein replacement. For example, thanks to donors like you, at this very moment in Boston, Massachusetts, Harvard scientists Dr. Jeannie Lee and Dr. Hungoo Lee are fine-tuning a Fragile X gene reactivation approach using a small molecule cocktail. We are confident that this and other strategies will eventually be ready for the clinic. And when they are, we will be ready, with clinical trial methods that have been tested and proven to be the best possible.

What FRAXA does is unique and essential to engineering a cure. These FRAXA-funded investigators and many, many others are hard at work at this very moment because of donors like you. Let’s keep them working. Let’s add more teams so that we have the best possible chance of bringing hope to families and friends affected by Fragile X.

THE AUTHOR

Explore Current Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.