A prospective, randomized, placebo-controlled evaluation of corticoneuronal response to intrathecal BDNF therapy in ALS using magnetic resonance spectroscopy: feasibility and results.
During the multicenter, phase III trial of intrathecal BDNF in ALS, we evaluated the neuronal marker N-acetylaspartate (NAA) as a surrogate marker of therapeutic efficacy using proton magnetic resonance spectroscopic imaging (MRSI) in a prospective and blinded manner. Selected subjects tolerated the study well without pump malfunction. The NAA to creatine (Cr) intensity ratio (NAA/Cr) was measured in the precentral and postcentral gyri, the superior parietal lobule, the supplementary motor area, and the premotor cortex. After 4.5+/-0.6 weeks treatment, NAA/Cr did not change significantly in any of the regions in the BDNF-treated group (n=5) compared to the placebo group (n=6). The lack of change in NAA correlated with the lack of clinical efficacy and supports the validity of NAA/Cr as a surrogate in this setting. MRSI is a feasible and safe method to evaluate intrathecal therapies in ALS.
Kalra
Sanjay
S
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Genge
Angela
A
Arnold
Douglas L
DL
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000737:chemistry; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D007278:Injections, Spinal; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009046:Motor Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010919:Placebos; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D010919:Placebos; D001224:Aspartic Acid; C000179:N-acetylaspartate