Related Experiment Video
Updated: Nov 16, 2025
CRISPR/Cas9 Technology in Restoring Dystrophin Expression in iPSC-Derived Muscle Progenitors
Published on: September 14, 2019
Risdiplam in Type 1 Spinal Muscular Atrophy
Giovanni Baranello1, Basil T Darras1, John W Day1
1From the Dubowitz Neuromuscular Centre, National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health University College London, and Great Ormond Street Hospital Trust, London (G.B.), Roche Products, Welwyn Garden City (M.E.-K.), and the Muscular Dystrophy UK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford (L.S.) - all in the United Kingdom; the Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan (G.B., R.M.), and the Pediatric Neurology Institution, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome (E.M.); the Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston (B.T.D.); the Department of Neurology, Stanford University, Palo Alto, CA (J.W.D.); Centre de Référence des Maladies Neuromusculaires, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles, Brussels (N.D.), the Neuromuscular Reference Center, Universitair Ziekenhuis Gent, Ghent (N.D.), and the Division of Child Neurology, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liege and University of Liege, Liege (L.S.) - all in Belgium; the Division of Pediatric Neurology, University Children's Hospital Basel (A.K.), Pharma Development Safety (M.G.), Product Development Medical Affairs-Neuroscience and Rare Disease (K.G., P.F.), and Pharma Development Neurology (R.S.S.), F. Hoffmann-La Roche, and Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel (O.K., H.K., T.S.), Basel, and Pediatric Neurology, Inselspital, University of Bern, Bern (A.K.) - both in Switzerland; the Discipline of Physiotherapy, Faculty of Medicine and Health, University of Sydney, Sydney (K.R.); and I-Motion, Hôpital Armand Trousseau, Paris (L.S.).
Background:
Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein.
Methods:
We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds.
Results:
A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study.
Conclusions:
In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).
More Related Videos
05:55Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice
Published on: October 3, 2011
06:51Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Related Concept Videos
01:21Satellite Stem Cells and Muscular Dystrophy
01:26Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
01:20Myasthenia Gravis: Overview and Treatment
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
01:21Rheumatic Heart Disease III: Medical Management
01:31Skeletal Muscle Relaxants: Therapeutic Uses