Neurology

Human sample and mouse studies identified a mAb against misfolded SOD1 that could help treat ALS harboring SOD1 mutations. Screening of memory B cells isolated from healthy elderly volunteers for mAbs that bind to misfolded SOD1 yielded a mAb that bound denatured misfolded SOD1 and oxidized misfolded human SOD1 with EC₅₀ values of 70 and 600 pM, respectively. In a transgenic mouse model of ALS expressing human G93A-mutant SOD1, intracerebroventricular infusion of a mouse version of the mAb decreased the severity of motor impairment and disease-associated body weight loss and increased survival compared with vehicle. Also in the model, i.p. injection of the mouse mAb delayed disease onset, decreased the severity of motor impairment severity and increased the weight of the gastrocnemius muscle and survival. In a transgenic mouse model of ALS expressing human G37R-mutant SOD1, the mouse chimeric mAb delayed disease onset, decreased motor impairment severity and increased the number of neurons in the ventral horn, the weight of the gastrocnemius and flexor digitorum longus muscles, and survival. Next steps by AL-S Pharma AG include testing the mAb in ALS patients.

Alexion Pharmaceuticals Inc. has the SOD1 inhibitor Decuprate bis-choline tetrathiomolybdate in Phase III testing for Wilson disease and preclinical testing for ALS...