MOTOR NEURON DISORDERS AND NEUROPATHIES: EP.244 Clinical characteristics of SOD1 and c9ORF72 positive ALS: findings from the Canadian neuromuscular disease registry

Abstract

The Canadian Neuromuscular Disease Registry (CNDR) is a nationwide neuromuscular disease registry. The CNDR collects data in affiliated clinics across Canada and currently has over 4100 total and 1500 ALS patients registered. Therapies for genetic-based ALS are under development targeting two of the most common genes associated with ALS, c9ORF72 and SOD1. The objective of this study is to characterize SOD1+ and c9ORF72+ ALS patients in Canada. Data from consenting ALS patients were recorded at 13 affiliated ALS clinics across Canada. Patients with a known SOD1 or c9ORF72 mutation and gender- and age-matched control individuals without a known genetic mutation or family history of ALS were included in the analyses. Progression rates were calculated in the first-year post-diagnosis by change in ALSFRS-R/time. Patients without multiple visits within the first-year post-diagnosis were excluded from progression analyses. Similarly, patients whose ALSFRS-R scores coincided with clinical trial participation were excluded from progression analyses. Baseline data from 25 SOD1 patients, 51 c9ORF72 patients, and 76 age- and gender-matched sporadic controls are presented. Median age at diagnosis was 58.3, 59.6, and 59.5 years for SOD1, c9ORF72, and controls respectively. SOD1 patients were 54% male, c9ORF72 65%, and controls 63%. Of the 25 SOD1 patients with mutation recorded, 48% had the Ile113Thr mutation. Progression analyses was performed on the subset of 12 SOD1 cases, 33 c9ORF72 cases, and 45 controls with complete data, and without clinical trial participation. ALSFRS-R progression rates were 1.0 points/month (range: 0-2.8) for SOD1, 1.2 points/month (0-3.4) for c9ORF72, and 0.9 points/month (0-2.4) for controls. Further longitudinal analyses incorporating potential confounders will be presented.