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Tay-Sachs, Canavan, GM1 and Sandhoff diseases

The Tay-Sachs Gene Therapy (TSGT) Consortium Results and Progress toward a Cure

In preparation for submission of an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) to conduct a clinical trial in Tay-Sachs disease patients, last fall the Tay-Sachs Gene Therapy (TSGT) Consortium scientists performed a final feasibility and safety study in non-human primates (NHP). During this study they were surprised to find severe neurological symptoms after injecting the vectors containing the genes. They found dramatic neuronal loss in the thalamus.  The TSGT Consortium scientific team believes that the toxicity in the NHP brain after gene transfer was caused by massive overexpression of the enzyme in the neurons that then triggered cell death.

The researchers of the Tay-Sachs  GeneTherapy Consortium are still committed to developing a safe and effective gene therapy for Tay-Sachs and related diseases. The team has developed a new plan to understand and resolve the unexpected adverse neurological response seen in unaffected primates and advance to clinical trials as quickly as possible. They are generating a panel of AAV vectors that have a broad range of gene expression and will assess their safety and efficacy in a stepwise manner as described in the following specific aims. NTSAD and Cure Tay-Sachs Foundation have each committed 50% of the budget needed to continue this important research.

Step 1: Test different vector combinations in special mice to find right  enzyme expression level with minimal toxic side-effects.

Step 2: Test new vector in primates with hopes it yields the desired enzyme expression with minimal toxic side-effects.

Step 3: Long term primate study of new vector with some dose escalation in preparation of clinical trial!

Each step is dependent on successful completion of the prior step so it is difficult to predict a timeline. These steps are also pending FDA feedback. 

Progress Reports

 View March 2014 progress report on Milestone I (.pdf).

 October, 2013 brief update: The TSGT team is testing a new panel of vectors in special mice to find the right enzyme expression level with minimal toxic side-effects. Results of the mouse studies are expected by January. The next step will be to test the top three new vectors in primates with hopes that at least one will yield the desired enzyme expression with minimal toxic side-effects. The TSGT team has always worked with dedication and passion although they are working with a renewed sense of urgency and purpose after Porter Heatherly, who has GM1, visited Dr. Martin's lab. Click here for the story.

View pdf February 2012 (72 KB) (.pdf)

View pdf  September 2011 (69 KB)  (.pdf)

View the full   pdf December 2010 (54 KB)  (.pdf) update on the progress with the animal trials and natural history study.

View pdf July 2010 (61 KB) (.pdf)

View pdf March 2010 (8 KB)  (.pdf)

View   pdf January 2010 (8 KB)  (.pdf)

Related Research Publications:

pdf Dramatic Phenotypic Improvement after Adeno-Associated Virus Gene Therapy in a Feline Model of Sandhoff Disease (54 KB)  (.pdf)

pdf Long-Term Phenotypic Correction of Feline Lysosomal Storage Disease by Intracranial AAV Gene Therapy (53 KB)  (.pdf)

pdf Gene Transfer Corrects Acute GM2 Gangliosidosis-Potential Therapeutic Contribution of Perivascular Enzyme Flow (790 KB)  (.pdf)

pdf Effective gene therapy in an authentic model of Tay-Sachs-related diseases (595 KB)  (.pdf)