Issue link: http://www.e-digitaleditions.com/i/399268
Julie Smith came to Raptor Pharmaceuticals in 2012 and currently serves as the company's President and CEO (designate). Ms. Smith aims to utilize her experience in drug development and commercialization for orphan diseases to bring promising drug therapies to patients with rare diseases around the world. Prior to her current position at Raptor Pharmaceuticals, Ms. Smith served as Chief Commercial Officer of Enobia Pharma, Inc., Vice President of Commercial at Jazz Pharmaceuticals, and led the global marketing efforts for enzyme replacement treatments at Genzyme General. HD Insights recently interviewed Ms. Smith about Raptor Pharmaceuticals' work with cysteamine bitartrate for HD. Below is an edited transcript of the conversation. HD INSIGHTS: How did you become interested in HD? SMITH: I first heard about HD from Abbey Meyers, who was one of the founders of the National Association of Rare Disorders (NORD). NORD was founded with the assistance of Woody Guthrie's widow, so HD was one of the first rare diseases put forward. Patient advocates came to the forefront and really pushed for policy changes and improvements that would help communities affected by rare diseases. When you hear the story of someone affected by HD, it leaves an indelible imprint on you. HD INSIGHTS: Can you tell us about the mechanism of action of cysteamine in HD? SMITH: Cysteamine, a prodrug of cystamine, mobilizes cysteine as it is metabolized. This is believed to have several therapeutic benefits. Firstly, the systemic increase in cysteine has been shown to have both a direct and indirect anti-oxidative effect to cells, while cysteine is rate-liming in the biosynthesis of glutathione, a potent anti-oxidant that has shown protective effects in patients with HD. Secondly, a recent paper published by Solomon Snyder at Johns Hopkins showed that individuals with HD have a major deficit of cystathionine gamma-lyase, which is essential for biosynthesis of cysteine, suggesting another reason that boosting systemic cysteine may be important in HD therapy. 1 Thirdly, cysteamine has been shown to up-regulate a number of the cell's own adaptive stress responses. Mutant huntingtin (mHTT) causes cell stress because the cell must deal with the mutant protein, which it does by forming aggregates. Aggregates of mHTT may trap other normally functioning proteins, and mHTT fragments are difficult for cells to process. Cysteamine up-regulates several heat shock proteins, which may help to normalize protein folding. Mis-folding is indeed a characteristic of mHTT. Finally, it has been observed that cysteamine increases the production and intracellular transport of brain-derived neurotrophic factor, which has also been shown to be deficient in the brains of individuals with HD and other neurodegenerative diseases. HD INSIGHTS: Please describe the design of your clinical trial. SMITH: The study was first conceived of and designed in 2010. The French members of the Huntington team had designed a proof-of-concept study, and the more they came to understand the biology of cysteamine, the more excited they became about its potential application in HD. They approached Raptor as we were forming a company, and requested access to RP103, to conduct a prospective placebo-controlled, 36-month trial in early-stage HD patients. The trial consisted of two separate segments: an 18- month placebo-controlled segment, followed immediately by an 18-month open-label, treatment segment with RP103. The primary objective of the trial was to measure the efficacy, safety, and tolerability of RP103 in the treatment of total motor deterioration, compared to placebo, at 18 months, which was the primary endpoint. Meet the CEO VITAL SIGNS NAME: Julie Smith, BS CURRENT POSITION: President and CEO (designate) of Raptor Pharmaceuticals EDUCATION: Bachelor of Science in Biological and Nutritional Science, Cornell University HOBBIES: Spending time with her two little boys, six and eight Copyright © Huntington Study Group 2014. All rights reserved. H D I N S I G H T S HD Insights, Vol. 9 12