current research
- Though there are currently no treatments for Tay-Sachs, there have been advances towards some brought through research. This research includes gene therapy, molecular chaperone, substrate inhibition, stem cells, and bone marrow transplant.
- The purpose of gene therapy is to restore the missing beta-hexosaminidase enzyme by introducing the right genetic code, causing the proper enzyme production to occur. The best way for the genetic code to be delivered is by using a viral vector. The virus is non-disease causing and is altered so that it contains the missing genetic code, and it is used as means to introduce the correct genetic information. The Tay-Sachs Gene Therapy Consortium has gotten positive results by using a gene therapy system called adeno-associated viral vectors in mice. They still haven't been able to see those same results in human patients. The main issue with gene therapy is that the FDA won't approve it for the market because they believe it's still in its experimental phase. Other challenges include the difficulty of creating effective vectors, the fact that the vector is only effective if introduced to a large amount of cells, it is hard to insert the gene into the correct brain cells, and the insertion of the gene could cause cancer.
- Molecular chaperone is currently being researched as potential therapy for adults with the Late Onset form of Tay-Sachs. Molecular/pharmacological chaperones are molecules that are small enough to cross the blood-brain barrier into the central nervous system. They attach to a non-functional beta-hexosaminidase enzyme, making it take the correct, functional shape. The issue with this type is that the enzyme must be present (which isn't the case for all Tay-Sachs patients), it only works with certain mutations, the wrong dose of chaperones can actually reduce enzyme function, and there is a lack of biomarkers (indicators in an organism).
- Substrate inhibition is where the small substrate inhibitor molecules slip through the blood-brain barrier into the central nervous system. Here, they decrease the amount of substrate (waste) that builds up. This research shows delayed symptoms and prolonged survival in their mouse models, but it hasn't always been successful with humans. One medicine, Zavesca, was given to patients as an inhibitor, but it showed no therapeutic benefit. The main challenge of substrate inhibition is trying to keep pace with the rapid substrate accumulation. Secondly, Zavesca also showed gastrointestinal side effects like diarrhea.
- Stem cells are being genetically altered to produce the missing beta-hexosaminidase enzyme and are sent to the central nervous system. Currently, this technique is being tested on animals. Unfortunately there are many challenges presented with this treatment, such as the immune system rejecting the cells; the cells may change in an unexpected way; different disease may be transferred through the stem cells; the ability to upscale the amount of cells needed by humans; and there is controversy over whether this method is moral.
- Bone marrow transplant is when a person with Tay-Sachs has marrow replaced with that of an unaffected individual donor that is capable of making the missing beta-hexosamindase enzyme. Right now, only two places conduct this procedure: Duke University Medical Center and the University of Minnesota. This is most likely the result of the fact that this procedure can have devastating effects on the patient, especially children. Most children die from this procedure's complications, because, for the healthy bone marrow to be introduced, the immune system has to be destroyed, lest it reject the new marrow.