Paper Showing Direct CNS Delivery of Gene Therapy Provides Enhanced Protection in a Severe Mouse Model of SMA.
January 18, 2012.
Gene replacement strategies have shown great promise in animal models of SMA. In this current study, the Lorson Laboratory used self-complementary Adeno Associated Virus expressing full-length SMN (scAAV9-SMN) to compare two different routes of viral delivery in a severe SMA mouse model. This was accomplished by injecting scAAV9-SMN vector intravenously (IV) - often referred to as systemic delivery, or intracerebroventricularly (ICV) - direct CNS delivery, into SMA mice.
Both routes of delivery resulted in a significant increase in lifespan and weight compared to untreated mice with a subpopulation of mice surviving more than 200 days. However, the ICV injected mice gained significantly more weight than their IV treated counterparts. Likewise, survival analysis showed that ICV treated mice displayed fewer early deaths than IV treated animals. Also, animals receiving ICV injections also had higher SMN protein levels in the brain and lumbar spinal cord as compared to IV injected animals.
Thus, the authors of the Lorson paper conclude that intrathecal delivery may prove to be a desirable route of administration should AAV gene therapy for SMA reach clinical trials ,and; collectively, this study demonstrates that route of delivery is a crucial component of gene therapy treatment for SMA.