Tay–Sachs disease is a rare autosomal recessive genetic disorder. In its most common variant (known as infantile Tay–Sachs disease), it causes a progressive deterioration of nerve cells and of mental and physical abilities that begins around six months of age and usually results in death by the age of four. The disease occurs when harmful quantities of cell membrane components known as gangliosides accumulate in the brain's nerve cells, eventually leading to the premature death of the cells. There is no known cure or treatment. Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimulus, known as the "startle response". There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.Infantile Tay–Sachs disease. Infants with Tay–Sachs disease appear to develop normally for the first six months after birth. Then, as neurons become distended with gangliosides, a relentless deterioration of mental and physical abilities begins. The child may become blind, deaf, unable to swallow, atrophied, and paralytic. Death usually occurs before the age of four.Juvenile Tay–Sachs disease. Juvenile Tay–Sachs disease is rarer than other forms of Tay–Sachs, and usually is initially seen in children between two and ten years old. People with Tay–Sachs disease develop cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity.Death usually occurs between the age of five to fifteen years.Adult/Late-Onset Tay–Sachs disease. A rare form of this disease, known as Adult-Onset or Late-Onset Tay–Sachs disease, usually has its first symptoms during the 30s or 40s. In contrast to the other forms, late-onset Tay–Sachs disease is usually not fatal as the effects can stop progressing. It is frequently misdiagnosed. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in adolescence or early adulthood – include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a schizophrenia-like psychosis.People with late-onset Tay–Sachs may become full-time wheelchair users in adulthood. Mutations in the HEXA gene cause Tay-Sachs disease. The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the brain and spinal cord. This enzyme is located in lysosomes, which are structures in cells that break down toxic substances and act as recycling centers. Within lysosomes, beta-hexosaminidase A helps break down a fatty substance called GM2 ganglioside. Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, which prevents the enzyme from breaking down GM2 ganglioside. As a result, this substance accumulates to toxic levels, particularly in neurons in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of these neurons, which causes the signs and symptoms of Tay-Sachs disease. Because Tay-Sachs disease impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Even with the best of care, children with Tay-Sachs disease usually die by age 4, from recurring infection.
Tay-Sachs disease is very rare in the general population. The genetic mutations that cause this disease are more common in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. The mutations responsible for this disease are also more common in certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana.
The concept of using gene therapy to treat Tay-Sachs disease is to use molecular trucks (vectors) 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.
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. Diseases 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.

Blogs on Tay Sachs
"The first clue that something might be wrong with Cameron was, oddly enough, a diagnosis of Tay-Sachs disease in her cousin.Cameron had just received a perfect report at her five-month checkup when her parents, Blyth and Charlie Lord, got the news about 18-month-old Hayden. The son of Charlie's identical twin brother, Hayden, had been misdiagnosed a few months earlier as having cerebral palsy before getting the news that he actually had Tay-Sachs, an extremely rare, fatal genetic disease that causes mental and muscular deterioration for which there are no treatments.e both parents must be carriers of the gene for the disease to be present, Blyth knew her own husband must also carry the gene. Blyth went to be tested at Brigham and Women's Hospital, and a month later, despite infinitesimal odds, found that she, too, was a carrier.That was more than 15 years ago, in the fall of 1999. Cameron lived another 18 months, dying four days after her second birthday. Yet Lord, who lives in Newton, says she, her husband and their two healthy teenage daughters still talk about Cameron everyday.

Bibliography http://en.m.wikipedia.org/wiki/Tay–Sachs_disease http://ghr.nlm.nih.gov/condition/tay-sachs-disease http://www.ninds.nih.gov/disorders/taysachs/taysachs.htm http://www.bizjournals.com/boston/blog/bioflash/2015/02/this-disease-takes-away-everything-one-familys.html?page=all
http://commonhealth.wbur.org/2011/11/tay-sachs-human-trial