Vamshi K Rao1, Kapil Arya2, Yohei Harada3, Nancy L Kuntz1, Christine J DiDonato1, Galia Napchan-Pomerantz4, Amit Agarwal5, Vikki Stefans6, Masahisa Katsuno7, Aravindhan Veerapandiyan2. 1. Division of Neurology, Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2. Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 3. Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 4. Department of Pediatric Pulmonology, Joe DiMaggio Children's Hospital, Hollywood, Florida, USA. 5. Division of Pulmonology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 6. Department of Pediatrics and Physical Medicine and Rehabilitation, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. 7. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract
BACKGROUND: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking. METHODS: This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy. RESULTS: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved. CONCLUSIONS: Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy.
BACKGROUND: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking. METHODS: This was a retrospective study describing our centers' experiences in treating SMA1 patients with combination therapy. RESULTS: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved. CONCLUSIONS: Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy.
Authors: Arlene M D'Silva; Sandra Holland; Didu Kariyawasam; Karen Herbert; Peter Barclay; Anita Cairns; Suzanna C MacLennan; Monique M Ryan; Hugo Sampaio; Nicholas Smith; Ian R Woodcock; Eppie M Yiu; Ian E Alexander; Michelle A Farrar Journal: Ann Clin Transl Neurol Date: 2022-02-16 Impact factor: 4.511