US Tax Deductible EIN: 26-0256621

- (562) 212-1071

- 2409 E. Luke Avenue Phoenix AZ 85016

US Tax Deductible EIN: 26-0256621

- (562) 212-1071

- 2409 E. Luke Avenue Phoenix AZ 85016

Gene Therapy

Gene Therapy activity for Tay-Sachs and Sandhoff is at a very high level and some clinical trials for your child may be available for you. This is a rapidly changing situation and somewhat complex. For the most up to date information, please call us at 562-212-1071 PT.

The science of gene therapy has been advancing very quickly over the past ten years. The concept of using gene therapy to treat Tay-Sachs disease is to use molecular trucks (vectors also referred to as viral vectors or AAV) to transport one or more therapeutic genes into diseased cells in the brain. Once inside the cells those vectors will direct the production of large amounts of normal Hex A enzyme, which will be distributed throughout the entire brain. This will lead to elimination of lysosomal storage in the brain, and possibly reversal of deficits and resumption of normal neurological development.

Tay-Sachs disease is an excellent candidate for gene therapy because:

  • Tay-Sachs is caused by mutations in a single gene (the Hex A gene). Therefore we only need to restore the activity of one enzyme, which can be accomplished by introducting one gene (hexA) or two genes (hexA and hexB simultaneously) since higher levels of HexA can be reached if both hex genes are introduced simultaneously into the target cells.
  • Cells have the ability to take Hex A from outside the cell and absorb it. If we can create Hex A in the brain, the cells are adept at picking it up and using it.

The gene therapy work that is most interesting to us is that of the Tay-Sachs Gene Therapy Consortium composed of researchers from seven highly regarded academic institutions (Auburn University, Boston College, Cambridge University, NYU, Massachusetts General Hospital, Harvard Medical School and University of Massachusetts). Their work as individual scientists has focused on lysosomal storage diseases (LSDs) affecting the brain. These researchers have combined their expertise with the goal of initiating a gene therapy clinical trial for Tay-Sachs disease (and Sandhoff disease) in early 2017. The Consortium's first year of reasearch was funded entirely by private sources (include $300,00 from the CTSF) at a cost of $423,000. But in 2009, the research team was awarded a four year $3.5 million grant from the NIH. The team found wonderful success with small animal models (mice) large animal models (cats) and even a rare breed of Jacob Sheep that where discovered to suffer from Tay-Sachs disease in 2009. This first year of research produced unbelievable success in small animal models and vector distribution throughout the brain. The second year of research focus on large animal models - and again the results where spectacular. However, as the team prepared to submit clinical trial request to the FDA in late 2012 - a problem was found. While testing a new vector delivery device that could pinpoint areas of the brain with more percision than ever before - the team found vectors injected into primate brains where causing unwanted symptoms. The primate brains where having and adverse reaction to the vectors. The finding where a complete suprise and the team determined it could not move forward safely without fully understand why the primate brain reacted differently that the mice, cats and sheep. And most importantly - how would the human brain react! 2013, 2014 and 2015 where dedicated to finding those answers.

In late 2015 the TSGT team believes it has created vectors that will not be toxic in primates - and ultimately humans. A new plan was established at a cost of $1,045,000 to move the project to clinical trials in early 2017. The new plan includes expanded testing, vector manufacturing and another Toxicity study all in hopes of gaining FDA approval for clinical trial. The team has gotten guidance from the FDA and believes it is following the "road map" set forth to be approved.

Here is how it might work. All the genes of a virus (adeno-associated virus) are removed and replaced with the HexA gene and other non-viral genetic elements necessary to direct production of the enzyme in infected cells. This is what is commonly known as a viral vector because of it is derived from a virus and it can shuttle (vector) genetic information into cells. The virus vectors carrying a normal HexA gene are then injected into the brain, and infected cells will start make large amounts of active HexA enzyme which is released into the brain. In essence the viral vectors turn brain cells into microfactories of normal enzyme in the brain. Diseased cells throughout the brain pick up this enzyme released from those manufacturing centers and use it to metabolize (recycle) GM2-ganglioside and eliminate this main product stored in their lysosomes. The concept is quite simple, and it has been demonstrated to be highly effective in treating mouse models of different lysosomal storage diseases, including GM2-gangliosidoses. Untreated GM2 mice (Sandhoff disease) die at 3-4 months of age. Members of the Consortium have shown that animals treated by the approach described above survive up to 2 years. Although treated animals still present movement abnormalities their lifespan has been increased by 8-fold!

Translation of this approach into an effective treatment in humans has considerable challenges:

  • Size - The human brain is ~2000-fold larger than the mouse brain.
  • Complexity The human brain anatomy is considerably different than the mouse.
  • Delivery modality Although it has been relatively easy to treat mice, the targets in the human brain will have to be carefully chosen to minimize risk and at the same time achieve global distribution of enzyme throughout the brain.
  • Timing of treatment Can severely affected patients resume normal development after treatment? Recent experiments in mouse models of LSDs indicate that the earlier the intervention is performed the better the outcome. This raises the question of when it may be too late to alter the course of disease?

We know gene therapy works in animals models. After the primate issues we need to safely upscale to larger animal models and ultimately human trials. The Tay-Sachs Gene Therapy Consortium has a fourteen month plan to prove the theory and develop a clinical trial protocol. Our is the research will meet FDA guidelines for clinical trial. The new plan cost $1,045,000 and does not include the cost of clinical trial - which may cost and additional million. We are hopeful that some of the larger pharmaceutical companies may be interested in funding the research as we near clinical trial.

One of the real benefits of gene therapy is that if we can prove that this therapeutic approach works in Tay-Sachs, the vectors can be packed with genes that would help other LSD diseases. From what will be learned during this pre-clinical and clinical studies we may be able develop treatments for many other neurological diseases including Parkinson's, Alzheimer's or multiple sclerosis (MS). Ongoing gene therapy trials in Parkinson´┐┐s patients have already shown hopeful results.

To read the detailed Tay-Sachs Gene Therapy Consortium project description click here.

Visit the Tay-Sachs Gene Therapy Consortium website at