Canavan disease is an autosomal recessive degenerative neurological disorder caused by defective ASPA gene. ASPA is responsible for the production of the enzyme aspartoacylase, an enzyme essential for breaking down concentrated brain molecule N-acetyl aspartate. The lack of this breakdown interferes with growth of myelin sheath of the nerve fiber, and as a result, symptoms appear in early infancy and progress rapidly, which may include mental retardation, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone, blindness, seizures, and ultimate early death.
To date, there is no cure or treatment for Canavan disorder.
In a collaborative research effort with Dr. P Leona investigative team at UNDMJ, the Samulski lab designed an AAV vector that efficiently transduces neuronal cells carrying the ASPA transgene under CMV promoter. After demonstrating safety and efficacy in non-human primates the Samulski lab produced FDA approved GMP vector in the UNC Vector core facility for Phase I clinical trial which was used in the first neuronal gene therapy trial in the US. The outcome of these studies were recently published in Science Translation were the investigators found that the gene transfer approach was safe, decreased N-acetyl-asparate, seizure frequency and provided clinical stabilization. Clinical stabilization was greatest in the youngest patients supporting that early detection and treatment with gene therapy-mediated enzyme replacement in neonatal period may offer the best opportunity for reduction of symptoms and long-term stability in patients with Canavan disease.
Full citation for the paper:
Paola Leone, David Shera, Scott W.J. McPhee, Jeremy S. Francis, Edwin H. Kolodny, Larissa T. Bilaniuk, Dah-Jyuu Wang, Mitra Assadi, Olga Goldfarb, H. Warren Goldman, Andrew Freese, Deborah Young, Matthew J. During, R. Jude Samulski and Christopher G. Janson. Long-Term Follow-Up After Gene Therapy for Canavan Disease. Sci Transl Med, Vol. 4, Issue 165, p. 165ra163, 2012. DOI: 10.1126/scitranslmed.3003454.
Read article on North Carolina Biotechnology website: "UNC's Samulski Parlays NCBiotech Support Into Cutting-Edge Gene Therapies"
Read article on the DNA Science Blog on the PLOS website: "Gene Therapy for Canavan Disease: Max’s Story"
Read article for Genomics on SciCasts website: "Gene Therapy Cocktail Shows Promise in Long-term Clinical Trial for Canavan Disease"
The Youtube video below was released by Science Translational Medicine Press and is a trailer adapted from a documentary to be released sometime in 2013.