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Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
- Source :
- New England Journal of Medicine. 377:1713-1722
- Publication Year :
- 2017
- Publisher :
- Massachusetts Medical Society, 2017.
-
Abstract
- Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve motor milestones and in death or the need for mechanical ventilation by 2 years of age. We studied functional replacement of the mutated gene encoding survival motor neuron 1 (SMN1) in this disease.Fifteen patients with SMA1 received a single dose of intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA encoding the missing SMN protein. Three of the patients received a low dose (6.7×10As of the data cutoff on August 7, 2017, all 15 patients were alive and event-free at 20 months of age, as compared with a rate of survival of 8% in a historical cohort. In the high-dose cohort, a rapid increase from baseline in the score on the CHOP INTEND scale followed gene delivery, with an increase of 9.8 points at 1 month and 15.4 points at 3 months, as compared with a decline in this score in a historical cohort. Of the 12 patients who had received the high dose, 11 sat unassisted, 9 rolled over, 11 fed orally and could speak, and 2 walked independently. Elevated serum aminotransferase levels occurred in 4 patients and were attenuated by prednisolone.In patients with SMA1, a single intravenous infusion of adeno-associated viral vector containing DNA coding for SMN resulted in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts. Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .).
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
medicine.medical_treatment
Genetic Vectors
SMN1
Spinal Muscular Atrophies of Childhood
CHOP
Disease-Free Survival
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Atrophy
medicine
Humans
Infusions, Intravenous
Motor skill
Mechanical ventilation
Nutritional Support
business.industry
Liver Diseases
Infant, Newborn
Historically Controlled Study
Infant
Genetic Therapy
General Medicine
Spinal muscular atrophy
Dependovirus
Motor neuron
medicine.disease
Respiration, Artificial
Survival of Motor Neuron 1 Protein
Surgery
030104 developmental biology
medicine.anatomical_structure
Motor Skills
Anesthesia
Female
Nusinersen
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15334406, 00284793, and 02122952
- Volume :
- 377
- Database :
- OpenAIRE
- Journal :
- New England Journal of Medicine
- Accession number :
- edsair.doi.dedup.....af15cdce58cda254901625ceb6b14cab
- Full Text :
- https://doi.org/10.1056/nejmoa1706198