Zavesca Clinical Trials for Tay-Sachs

                Beginning in 2003, clinical trials for a new drug called Zavesca were being conducted here in the United States at New York University School of Medicine and Cleveland University Hospital.  At that time, this drug was being used in Europe to help those affected with the Late Onset Tay-Sachs disease, so the United States decided to begin tests here to see if this is a possible treatment or cure for this disease that would be safe enough for Americans to use. According to doctors and scientists in Europe, this drug is helping Late Onset Tay-Sachs patients with their gait and motor function.

                Zavesca is a substrate reduction or inhibitor therapy pill that appears to work best for those with the Late Onset Tay-Sachs. This drug reduces the buildup of GM2 ganglioside aiding in the neurological functioning of these patients. Zavesca’s chemical name is OGT918 or miglustat and comes in pill form as a 100 mg capsule, but has been used as crushed pill forms for the clinical trials involving those babies affected with Tay-Sachs disease.

                There are some very serious side effects associated with the use of Zavesca such as extreme nerve damage that may result in numbness, tingling, burning sensations, and tremors in the hands and feet. Some not so serious side effects include, but are not limited to: diarrhea, constipation, problems with vision, abdominal pain, weight loss, dizziness, headaches, and muscle weakness. As with any medication, there is a possibility of severe allergic reactions that could cause extreme swelling of the throat and difficulty breathing, as well as hives and redness.

                Due to the complexity and newer release of Zavesca here in the United States of America, this medication can be very, very expensive for patients who do not have health insurance, or who do have health insurance, but this medication is not covered. On average, Gaucher patients take one 100 mg capsule three times daily. Each pill costs about $110 totaling at about $330 a day to take this medication. Amazingly, this medication is one of the cheapest options in its class and is usually the first recommended medication for those suffering from Gaucher disease.

                There must be real hope for this drug because in 2005, scientists decided to have clinical trials with Zavesca for infants affected with the Tay-Sachs disease and they crushed the capsules and administered the medication orally or through feeding tubes. For today though, Zavesca is not used for the treatment of any level or stage of Tay-Sachs and is only approved for the use in patients suffering from Gaucher disease and is only used if enzyme replacement therapy was unsuccessful or not a feasible option. However, research and clinical trials are still being conducted to hopefully find a treatment or cure for Tay-Sachs disease.  

Substrate Reduction Therapy Research

                Last week, stem cell gene therapy was discussed as a current research topic for the curing and/or treating of Tay-Sachs disease. There are many other therapies and drugs being researched and tested in hopes of finding a cure for this illness. Another research theory is the idea of using substrate reduction therapy to help those infants affected with Tay-Sachs.

                Substrate reduction therapy is centered on the idea of lowering the rate of ganglioside production to better match the level of residual hex A enzyme in the nerve cells found in the brains of patients suffering from Tay-Sachs. The ideas of substrate reduction therapy was thought of in the early 1980s, but there were mixed emotions regarding this notion and so it took a while before scientists and researchers decided to test the idea. The problem with substrate reduction therapy for patients suffering from Tay-Sachs disease is the amount and time at which it is used on a patient. The lipids which make up the phospholipid bilayer around cells may be distorted and cellular production and differentiation could be disturbed.

                The main downside about substrate reduction therapy is the fact that this is yet another therapy that has a hard time passing through the blood-brain barrier. This treatment has been useful for those affected with Gaucher disease which is similar to Tay-Sachs in how both have enzyme production abnormalities. However, the big difference is that Gaucher disease does not stem from the brain, but rather the spleen. This treatment is said to have helped close to 3,000 people worldwide affected with Gaucher disease. Maybe one day Tay-Sachs will have a cure found like this one that is being used for the Gaucher disease.

                Substrate reduction therapy is not available at this time to those diagnosed with Tay-Sachs disease. It is still being tested on mice and primates, but scientists and researchers are hopeful that the FDA will allow them to extend studies to clinical trials, but when and really even if that will happen is still a big question being asked. It is also being discussed that perhaps no one treatment will slow, stop, or reverse the Tay-Sachs disease, but rather a combination of various drugs and therapies.   

Tay-Sachs Disease Stem Cell Gene Therapy Research

                At this time, there is no known cure for Tay-Sachs disease. There are medications only available to help make the patient more comfortable and able to function a bit better. However, scientists, doctors, and researchers are working together to find a cure for this illness and they have been coming up with some cutting-edge techniques and research theories. Some of these studies include stem cell therapy to help slow or reverse the effects of Tay-Sachs disease.

                There is research being done with adult stem cells, umbilical stem cells, and Hematopoietic stem cells which are cells that have not differentiated yet. It is hoped that stem cells could help replace genes that are defective or mutated such as the Tay-Sachs mutation. There has even been research on using stem cells to regrow tissues and neurons. Scientists are hopeful, but they have said on many occasions that any cures resulting from stem cells are still many years of research and experiments away.

                There are many controversies with the use of stem cells in research to cure diseases and illnesses. Many are ethical and moral issues involving the type of stem cells used and in what way they are being utilized. A large barrier to using stem cells for treatment is that we still don’t know enough about these cells and what they can and cannot do. It’s difficult to just put something into someone’s body when we do not fully understand the pros and cons of that treatment.  

                When it comes to Tay-Sachs, scientists are running into challenges with how to best insert the stem cells into the brain of an affected person and having the cells aid in transport of genes and enzymes into the correct neurons. Also, it’s difficult to find a cure or therapy that can be inserted into the bloodstream and then cross the blood brain barrier. This is a very, very selective barrier the brain has so as to protect this vital organ from bacteria and diseases that may be in the blood itself, but this is what makes treatments difficult to work properly. Tay-Sachs results from problems in the brain itself, and if the treatment cannot simply be inserted into the bloodstream and pass this barrier, it becomes so much more difficult to administer therapy effectively and safely. This barrier is there for a reason and to just manually insert the stem cells into the brain may increase the likelihood of infection and bacteria getting into the brain which is potentially fatal. Also, the brain is less likely to accept the new stem cells when they did not “naturally” come into the brain via normal passageways.  

                Stem cell research is looking more and more like a possible treatment for not only Tay-Sachs, but other diseases and illnesses, as well. There is still a long road ahead of research studies and experiments and treatment trials with stem cell therapy and transplantation.