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On the Shoulders of Giants

2019 started with the exciting announcement that our 2018 research awards totaled $10 million! We take our hats off to the hundreds of Rett families who put their urgency and passion to work raising funds and to our colleague, Tim Freeman, who leads this impressive effort. Although we personally are typically not involved with RSRT’s fundraising activities we can imagine how difficult it is to raise the dollars necessary to support our Roadmap to a Cure. It is our responsibility to wisely invest your fund raising dollars – and it is a responsibility we take very seriously.

Be Vigilant for Breakthrough Discoveries! This is a vital ideal that we all share and try to live up to every day. When we identify a discovery that can be applied to Rett Syndrome, we actively recruit the pioneering researchers to our cause - with a primary emphasis on therapeutics that could be curative. Recruiting leading scientists’ focus and energy to Rett isn’t always easy, as other disorders with less hurdles to jump are often more attractive. So it’s fortunate that we are a tenacious bunch. The proposals funded this year are a direct product of this proactive and sometimes relentless strategy.

We have been carefully monitoring progress with CRISPR, meeting with the leading scientists and encouraging them to apply CRISPR to Rett. Fortunately, CRISPR technology has now expanded to allow CRISPR to function like an eraser rather than a scissor, an important development that opens the door for difficult-to-treat neurological disorders. The awards to Beam Therapeutics and MIT leverage these recent scientific discoveries and aim to correct mutations that cause Rett Syndrome in brain cells at the level of both DNA and RNA.

The two awards to UMass Medical School, take advantage of top talent in their RNA Therapeutics Institute, where Nobel Prize winners and CRISPR company founders expand scientific knowledge every day. One program aims to replace the entire section of MECP2 DNA where most mutations occur with a normal section that is mutation free. This approach would allow 97% of our Rett patients to be treated with just one gene editing approach! The other UMass program aims to trick MECP2 mutant cells into ignoring their mutation and making functional protein. Although this particular approach would benefit only those patients with certain mutations (those that end in X), about 1/3 of the Rett patient population could be helped. This program will use a treatment that the FDA is already familiar with, which would speed development if it proves to work in Rett.

Importantly, all of these approaches will only correct cells that make mutant MECP2, which reduces the risk of making too much MECP2, thereby providing a potential advantage over current gene therapy approaches.

Our primary goal in funding cutting-edge research programs like these is to advance them to a stage where biopharma companies can take them forward. The success of our Gene Therapy Consortium 1.0 in partnering with AveXis/Novartis is proof that this is possible – a strategy we seek to repeat with all of our curative approaches. Our ultimate goal is to deliver life-altering therapeutics as soon as possible. We won’t rest until we have achieved that.