Viral vector containing DNA coding for the human SMN protein; for treatment of 5q spinal muscular atrophy

Professor Mimoun Azzouz, University of Sheffield

10th May 2014

TACT reviewed an application from Professor Azzouz who has developed a AAV9 viral vector (AAV9-) expressing DNA for the human Survival Motor Neuron (SMN) transgene for the treatment of spinal muscular atrophy. To date, Professor Azzouz’s group have (i) performed studies to scale up GLP and GMP AAV9 vector production; (ii) preliminarily demonstrated that scAAV9-SMN can extend the lifespan in SMNΔ7 mice; (iii) worked on dose-response efficacy studies to determine the optimal dose for future preclinical studies; (iv) planned regulatory GLP toxicology and biodistribution studies in rodents; and (v) worked on a dossier submission for a Biologics Licence Application (BLA) to initiate a phase I trial in SMA patients. Overall, TACT believes this is a promising approach to treat a devastating disease. However, TACT recommended that several issues should be considered before moving into the clinic. Specifically, planning for the preclinical toxicology studies will depend on identifying the preferred dose range for the clinical trial. Therefore, generating additional data to support dose selection should strategically best occur as one of the next steps.

 
12 Apr 2017