The most recent advances have been especially exciting. The first clinical trial partially funded and approved by the Food and Drug Administration (FDA) and the National Institute of Health (NIH), in which a new and more potent viral vector is being used to transport the genes into the brains of Canavan children, is ongoing at the Robert Wood Johnson Medical Center. Many of the children have been monitored, and the parents of each and every child are reporting clinical improvement, as supported by MRI and MR spectroscopy scans. Lindsay Karlin, now eleven years old and the first child treated in the first trial in 1996, has shown no deterioration since receiving the latest gene vector. Researchers expect to use the findings from this study to apply to research for other, more common diseases, including Parkinson's Disease, Alzheimer's Disease, multiple sclerosis and stroke.
Stem Cell Therapy
The Canavan Research Foundation is also supporting stem cell therapy, the transplantation of normal neural stem cells into the brain. Stem cells have the potential to develop into any type of cell, and the research teams that we are supporting are currently developing stem cells that will take over for the faulty cells in the brains of Canavan children and produce the enzyme that the children lack. We are focused on identifying and supporting researchers who demonstrate the greatest potential to bring their work to clinical trial in the next two years. Stem cell therapy may also hold the key to curing a host of other diseases, including genetic and degenerative diseases, stroke and traumatic brain and spinal cord injury.
Our objective is to speed up research through private funding so that it may become available as quickly as possible to those who need it, adults and children like Lindsay whose time is running out.
University of Medicine & Dentistry of New Jersey / Robert Wood Johnson Medical School, Director of the Cell & Gene Therapy Center and Associate Professor, Neurosurgery; Coriell Center for Medical Research, Adjunct Member
Following post-doctoral studies in Montreal, Dr. Leone was an Associate Research Scientist at Yale University from 1996-1998. From 1998-2001, she was Associate Director of the CNS Gene Therapy Center at Jefferson Medical College and an Assistant Professor in the Department of Neurosurgery. Dr. Leone has been responsible for the development and characterization of viral (AAV, adenovirus, retrovirus) and non-viral vectors for the treatment of Canavan Disease and other disorders. At Yale and Thomas Jefferson Universities, she was the IND/FDA sponsor of two separate 'Gene Therapy for Canavan Disease' studies.
Dr. Leone is currently Principal Investigator on the Canavan gene therapy protocol using adeno-associated viral vectors. Her laboratory is conducting in-vivo studies of both viral vectors and stem cells and their use in neural transplantation for therapeutic applications on a variety of neurodegenerative disorders, brain and spinal injuries and stroke. She also leads investigations on pharmacological, genetic and stem cell therapies on animal models of Canavan Disease, Amyotrophic Lateral Sclerosis, Parkinson's Disease, Tay Sach's Disease and other neurological disorders. For more information on the research initiatives led by Dr. Leone, please click here for the Cell & Gene Therapy Center.
Please click the links below for scientific abstracts published by Dr. Leone and her team.
Janson et. al. "Lithium Citrate for Canavan Disease." Pediatric Neurology (15 Apr 2005). 33(4):235-243.
Janson et. al. "Gene Therapy of Canavan Disease: AAV-2 Vector for Neurosurgical Delivery of Aspartoascylase Gene (ASPA) to the Human Brain." Human Gene Therapy (20 Jul 2002). 13:1391-1412.
Leone et. al. "Aspartoascylase Gene Transfer to the Mammalian Central Nervous System with Therapeutic Implications for Canavan Disease." Annals of Neurology (2000). 48(1):27-38.
Leone et. al. "Global CNS gene transfer for a childhood neurogenetic enzyme deficiency: Canavan Disease." Current Opinion in Molecular Therapeutics (1999). 1(4):487-492.
McPhee et. al. "Effects of AAV-2-mediated aspartoascylase gene transfer in the tremor rat model of Canavan disease." Molecular Brain Research (2005). 134:112-121.
Tavazzi et. al. "Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism." Clinical Biochemistry (4 Aug 2005).
Evan Y. Snyder, M.D., Ph.D.
Harvard Medical School, Professor of Pediatrics, Pediatric Neurology, Neonatology; Director, Stem Cells and Regeneration Program, The Burnham Institute
Dr. Snyder is the world-renowned leading researcher and co-founder of the stem cell field. His work focuses on understanding the mechanisms underlying Canavan disease and other childhood neurodegenerative diseases. Dr. Snyder's work investigates Canavan at a molecular and cellular basis - particularly as programmed into the central nervous system at the stem cell level. Dr. Snyder's work focuses on studying implanted stem cells in Canavan animal models with the goal of treating afflicted Canavan children. For more information on the research initiatives led by Dr. Snyder as well as scientific literature published by his team, please click here for the Synder Lab at the Burnham Institute.