Vitamin D Is A Prognostic Factor Of Amyotrophic Lateral Sclerosis And Confers Protection To Motoneurons In Vitro (P4.084)

OBJECTIVE: To study prognosis of amyotrophic lateral sclerosis (ALS) patients according to plasma vitamin D (VD) levels and to determine the effect of VD on motoneurons (MNs) in vitro for both survival and neuroprotective effects. BACKGROUND: ALS is a rapidly evolving and incurable MN disorder with a highly variable prognosis, ranging from 3 months to more than 20 years. There is to date no consensus biomarker linked to ALS prognosis. The detrimental consequences of VD deficiency have been documented in several neurological diseases, such as multiple sclerosis, Alzheimer’s disease, stroke or Parkinson’s disease. DESIGN/METHODS: 74 ALS patients had plasma VD level measurement and were followed quarterly. Prognosis was studied according 2 parameters: 1) survival; 2) rate of decline, defined by the number of ALSFRS-R points lost each month. Purified MNs from mice embryos were cultured for 48hrs and 1,25(OH)2D3 (the biologically active hormone) was added at progressive concentrations to evaluate MN survival and MN protection against Fas-ligand induced apoptosis. RESULTS: ALS patients with a severe VD deficiency (SVD, < 25nmol/L) had a 4 times higher rate of decline compared to patients with normal VD levels (NVD, 1.42 vs 0.36, respectively, p=0.00013). In the NVD group, median survival was 52.8 vs 29.5 months for SVD patients (log rank, p=0.002). After adjustment for age at onset, risk of death was increased in SVD patients compared to those with NVD (Cox proportional hazard, HR 5.9, 95% CI 1.4 to 24.3; p=0.01). In vitro, VD significantly potentiated the effect of neurotrophic factors (+ 40 % survival at 100 nM, p<0.001) and completely prevented MNs from Fas-induced death (p<0.001). CONCLUSIONS: Our findings suggest that vitamin D as a reliable prognostic factor of ALS and support a neuroprotective function of vitamin D on MNs in vitro. Study Supported by: Disclosure: Dr. William has received personal compensation for activities with Novartis, Merck & Co. Inc., Sanofi-Aventis Pharmaceuticals Inc., Biogen Idec, and Actelion. Dr. Tremblier has nothing to disclose. Dr. Plassot has nothing to disclose. Dr. Alphandery has nothing to disclose. Dr. Salsac has nothing to disclose. Dr. Pageot has nothing to disclose. Dr. Juntas-Morales has nothing to disclose. Dr. Scamps has nothing to disclose. Dr. Daures has nothing to disclose. Dr. Raoul has nothing to disclose.