Molecular therapies for HD – Ready, Set and GO!

Huntingtin targeting therapeutics are entering the clinical realm… after many years of work, 4 big players in the biotech/pharmaceutical industry are planning clinical trials in HD. Recently you might have heard about Roche, the Swiss pharmaceutical giant, acquiring the rights to develop ISIS’s lead antisense molecule to lower HTT expression in clinical studies. This represented a milestone for CHDI as well, as initialy one of the goals of the donors and of CHDI’s president, Robi Blumenstein, was to enable and fund work to a level of maturity where a large company would become interested in developing a therapy for HD. As with the Pfizer new PDE10 inhibitor drug, CHDI has succeeded in getting a lot of attention from big players in the drug development world. Even before Roche acquired ISIS HD program (set to start trials in 2014 we hope), the orphan-disease pharmaceutical company Shire acquired the rights to develop Sangamo’s exciting zinc finger protein (ZFP), the most advanced allele-specific molecule in clinical development. CHDI continues to work with Sangamo and Shire to bring this therapy to patients as soon as possible. The ZFP developed collaboratively with Sangamo has shown efficacy in vivo in HD models, and the prospect of testing it in the clinic in the next couple of years is extremely exciting.

Two other players are also in the game for being the first to take a molecular therapy for HD to the clinic. Medtronic and CHDI continue to work to develop a surgically-delivered siRNA molecule into patients in 2014. And the latest to enter the game, Genzyme and Sanofi-Aventis, are also in late preclinical studies. All in all, the meny is varied and plentiful. Lets remain optimisitc that one of these experienced players will succeed. The stakes are high, and so are the risks (this type of therapy has never been attempted before in a brain chronic disorder), but equally high is the enthusiasm and the promise of effective, and long-lasting, treatment if they work. To enable this process, CHDI has assembled a ‘biomarker task force’, headed by CHDI’s chief medical officer (Cristina Sampaio) and chief scientific officer (Robert Pacifici). The goal of this task force is to bring the world’s experts in HD and other fields, to identify how best to measure that these therapeutic approaches yield a change in the slope of the progression, or to monitor for a biological effect of lowering HTT in the brain. Not an easy task, but one that is essential for the success of these trials. in the 5+ years I have been leading CHDI’s drug disocvery programs, this is by far the most exciting and challenging year, but one that fills me with hope.