Survival and Disease Progression in SOD1 Familial ALS in North America (P3.185)

Objective: The goal of this study is to establish well-documented and recently updated data on the natural history of amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALS-SOD1), including age of onset, survival, respiratory function, and ALS function rating scale (ALSFRS) scores, in order to facilitate the design of future ALS-SOD1 clinical trials. Background: ALS is an adult-onset neurodegenerative disease affecting upper and lower motor neurons, resulting in severe weakness and fatal respiratory failure within 2-5 years. The launch of treatment trials for ALS-SOD1 requires accurate natural history of the disease to define the number of patients needed to determine a change in clinical course and to provide historical control data. Design/Methods: Data were collected via a multicenter retrospective chart review of ALS patients with genetically confirmed SOD1 mutations, cared for after the year 2000 at 15 North American medical centers. A total of 173 ALS patients with SOD1 mutations, including 63 SOD1A4V patients, were analyzed. Genetic testing was performed by individual institutions at the time of diagnosis. Results: Age of onset for all ALS-SOD1 patients was 49.4+/-12.1 years. For SOD1A4V, a mutation known for an exceptionally aggressive disease course, age of onset was 49.5+/-12.4 years. Mean disease duration was 4.6+/-6.1 years for all SOD1 positive, and 1.4+/-0.7 for SOD1A4V. Mean rate of decline for ALS-FRS was -0.9+/-1.3 points/month for all SOD1 and -3.6+/-5 points/month for SOD1A4V. Mean rate of decline for predicted forced vital capacity (FVC) was -2.4+/-3.0 /month for all SOD1 and -11.0+/-13.1 /month for SOD1A4V. Conclusions: Our data demonstrate that SOD1A4V is particularly aggressive and a relatively uniform subset of ALS. Our calculated overall survival for SOD1A4V is approximately 1.4+/-0.7 years, similar to previous data (1.4+/-0.9 years). Our results provide updated ALS-SOD1 natural history data that will be important for designing clinical trials in ALS-SOD1 patients. Disclosure: Dr. Bali has nothing to disclose. Dr. Self has nothing to disclose. Dr. Siddique has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Ratti has nothing to disclose. Dr. Boylan has received research support from Biogen Idec, Cytokinetics, Inc., and Neuraltus Pharmaceuticals, Inc. Dr. Glass has nothing to disclose. Dr. Maragakis has received personal compensation for activities with Advanced Technologies and Regenerative Medicine LLC. Dr. Caress received personal compensation for activities with Glaxo-Smith-Kline and Biogen Idec. Dr. Scherer has received personal compensation for activities with Simon-Kucher & Partners LLC as a consultant. Dr. Appel has received research support from Neuraltus, Inc., and GlaxoSmithKline. Dr. Wymer has received personal compensation for activities with Otsuka, Serono, and Novartis as a consultant. Dr. Gibson has nothing to disclose. Dr. Zinman has nothing to disclose. Dr. Mozaffar received personal compensation from Genzyme Corporation and Grifols for speaking engagements and has served as an advisory board member for Amicus, Biogen idec, Biomarin, Genzyme, Idera Pharmaceuticals and Ultragenyx. Dr. Mozaffar has receive Dr. Jockel-Balsarotti has nothing to disclose. Dr. Allred has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Fisher has nothing to disclose. Dr. Lopate has received research support from Immunex Corp., and Baxter Laboratories. Dr. Pestronk has received personal compensation for activities with Athena Diagnostics. Dr. Cudkowicz has received personal compensation for activities with GlaxoSmithKline, Biogen Idec, Teva Neuroscience, and Cytokinetics. Dr. Miller has received licensing fees from C2N Diagnostics.