• Christian Mueller, James D Berry, Diane M McKenna-Yasek, Gwladys Gernoux, Margaret A Owegi, Lindsay M Pothier, Catherine L Douthwright, Dario Gelevski, Sarah D Luppino, Meghan Blackwood, Nicholas S Wightman, Derek H Oakley, Matthew P Frosch, Terrence R Flotte, Merit E Cudkowicz, and Robert H Brown.
• From the Horae Gene Therapy Center, Department of Pediatrics, University of Massachusetts Medical School (UMMS) (C.M., G.G., M.B., T.R.F.), and the Department of Neurology, UMMS and UMass Memorial Medical Center (D.M.M.-Y., M.A.O., C.L.D., N.S.W., R.H.B.), Worcester, and the Healey Center for ALS, Department of Neurology (J.D.B., L.M.P., D.G., S.D.L., M.P.F., M.E.C.), and the C.S. Kubik Laboratory for Neuropathology (D.H.O., M.P.F.), Massachusetts General Hospital and Harvard Medical School, Boston.
• N. Engl. J. Med. 2020 Jul 9; 383 (2): 151158151-158.

AbstractTwo patients with familial amyotrophic lateral sclerosis (ALS) and mutations in the gene encoding superoxide dismutase 1 (SOD1) were treated with a single intrathecal infusion of adeno-associated virus encoding a microRNA targeting SOD1. In Patient 1, SOD1 levels in spinal cord tissue as analyzed on autopsy were lower than corresponding levels in untreated patients with SOD1-mediated ALS and in healthy controls. Levels of SOD1 in cerebrospinal fluid were transiently and only slightly lower in Patient 1 but were not affected in Patient 2. In Patient 1, meningoradiculitis developed after the infusion; Patient 2 was pretreated with immunosuppressive drugs and did not have this complication. Patient 1 had transient improvement in the strength of his right leg, a measure that had been relatively stable throughout his disease course, but there was no change in his vital capacity. Patient 2 had stable scores on a composite measure of ALS function and a stable vital capacity during a 12-month period. This study showed that intrathecal microRNA can be used as a potential treatment for SOD1-mediated ALS.Copyright © 2020 Massachusetts Medical Society.

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