Drug treatment with VPA in SMA1 infants

A clinical trial designed to evaluate the combination of Valproic Acid (VPA) and L-Carnitine for the treatment of Spinal Muscular Atrophy in infants with Type I SMA, called Carni-Val Type I, is being conducted by the Project Cure SMA group, fully funded by Families of SMA. Specifically this trial will assess the safety of VPA and L-Carnitine in infants and develop improved methods to assess the strength and motor abilities of severely affected infants.

Sandra Reyna, clinical trials Manager, said: “This trial sets the stage for future successful multi-center clinical trials in children with SMA Type I. We hope that the successful completion of this clinical trial will reduce barriers to future studies in SMA infants for new therapies currently under development”.
Thirty-six infants with SMA Type I, ages 2 weeks to 12 months have been enrolled in the trial at North American sites and trial recruitment here is closed at this time. Enrolled infants receive drug treatment for 12 months. The trial will be completed in the fall of 2010 and results released in 2011.
Dr. Kathryn Swoboda, Principal Investigator for Project Cure SMA said: "We are very pleased to have successfully reached our target enrollment in the SMA CARNI-VAL Type I trial. This achievement represents a monumental effort on the part of coordinators, investigators and families, who worked closely together to meet the needs of these fragile infants and enable their participation. This milestone should prove invaluable in helping us to effectively measure meaningful change in outcomes for those most severely affected by this devastating disease”.

Meanwhile, a study has been published in the journal Neurobiology of Disease on September 4 with negative results about treatment with VPA in SMA patients. The paper “Valproic acid blocks excitability in SMA type I mouse motoneurons” has published by a research team of the University of Wuerzburg, Germany. Valproic acid (VPA), an antiepileptic drug and HDAC inhibitor, has been identified as a drug candidate for spinal muscular atrophy. Based to its potential to up-regulate SMN expression from the SMN2 gene in fibroblasts and lymphoblastoid cell lines from SMA patients, the researchers analysed the effects of VPA in isolated motoneurons from mice of a model for SMA type I. Treatment with VPA increased SMN expression but unexpectedly also led to reduced growth cone size and reduced excitability in axon terminals of mutant motoneurons. The data indicate effects of VPA which might aggravate disease specific symptoms in SMA patients.

(sources: Families of SMA, PubMed)