Tay-Sachs

=Tay-Sachs Disease: Hoping For A Cure= Gabrielle Javier 12/9/2010


 * Abstract:**

Tay-Sachs Disease is a merciless killer among young children. It is characterized by a slow decline of the nervous system that leaves the child unable to perform any basic functions like swallowing, breathing, or grasping things with hands. Once diagnosed with TSD, an infant’s life expectancy is 2 to 5 years. Few treatments are successful at prolonging life and no cures currently exist.


 * Introduction:**

When I started this research project, Tay-Sachs Disease interested me in a strictly academic way, but did not take long for the severity of this genetic disease to hit me. Reading about the cruel facts and listening to the tragic stories left me feeling frustrated by the hopelessness of this disease. As they become progressively incapacitated by the degeneration of their nervous system, children are missing the everyday joys of growing up. I am unfortunately one of many people worldwide that are just learning about TSD and its devastating effects. My hope is that the word is spread and the treatments are found so all of the individuals suffering from TSD can live a normal life.


 * Discussion:**

Tay-Sachs Disease is a genetic neurodegenerative disease that is progressive. Infantile and Juvenile Tay-Sachs is fatal.
 * //What Is Tay-Sachs Disease?//**

In a family where only one parent carries the Tay-Sachs gene, 50% of the offspring will not inherit the gene, and 50% will inherit the gene, but will remain unaffected. However, in a family where both parents carry the gene, 25% of the offspring will not inherit the gene, 50% will inherit the gene, and 25% will receive the gene from both parents and will be affected by Tay-Sachs Disease.
 * //Genetic Pre-Disposition//**

The populations that are most at risk for carrying the Tay-Sachs gene are Ashkenazi Jews (from Eastern Europe), Louisiana Cajuns, and French Canadians. According to //Cure Tay-Sachs Foundation//, 1 out of 27 Ashkenazi Jews, French Canadians, or Louisiana Cajuns carries the gene; 1 out of 50 Irish-Americans carries the gene; 1 out of 250 Americans carries the gene. (CTSF)
 * //At Risk Populations//**



TSD is caused by a deficiency of an enzyme known as Hexosaminidase A, or Hex-A. Lack of production of this enzyme is coded by a defected gene on chromosome 15. (National Human Genome Research Institute) In a normal person’s cell, Hex-A is responsible for breaking down GM2 ganglioside (a lipid) in the lysosomes. In an individual suffering from TSD, the absence or insufficient levels of Hex-A means that gangliosides are not broken down, thus accumulating in the lysosomes. It is the accumulation that damages the cells – particularly nerve cells – and it is the damage to these nerve cells that causes the debilitating symptoms.
 * //What Is The Cause?//**

The damage to the nerve cells and brain cells causes the gradual breakdown of the nervous system. Symptoms vary depending on the particular type and individual experience of TSD. (NTSAD)
 * //What Are The Symptoms?//**

__//Classic Infantile Tay-Sachs//__ A baby with Infantile TS appears to develop normally up to 6 months of age. By 2 years old, the child may have lost muscle tone (hypotonia) and muscle control, resulting in the inability to sit, crawl, or turn over. Often times, seizures become common. A decreasing field of vision and mental capacity will ultimately leave the child blind, mentally impaired, paralyzed and non-responsive. (NTSAD) The child will have trouble breathing or swallowing. Infantile TS slowly ends a child’s life between 2 and 5 years of age. (National Human Genome Research Institute) Complications from breathing (Aspiration Pneumonia) can also cause death. (Cleveland Clinic)

__//Juvenile Onset Tay-Sachs//__ Symptoms become apparent between 2 and 5 years of age, at a slower rate that that of Infantile TS. The regression may start with incoordination and trouble with walking. (Cleveland Clinic) Throughout late childhood and adolescence, the some of the Classic symptoms develop, although a bit milder. While vision, hearing and most mental functions remain unaffected, the decline includes loss of muscle and mental capacity, and slurred speech. (NTSAD) Death – often a result of infections – usually occurs in adolescence. (Cleveland Clinic)

__//Adult/Late Onset Tay-Sachs (LOTS)//__ LOTS is the most rare form of Tay-Sachs and symptoms mostly start appearing in adolescence. The most common symptoms are slurred speech, loss of muscle and muscle control, and erratic coordination, so it is often misdiagnosed. Additionally, symptoms are accompanied by psychological difficulties. (Cleveland Clinic) Because LOTS is caused by a Hex-A deficiency – rather than a complete absence – the results are less devastating, and do not end in death. (NTSAD)


 * //How Is Tay-Sachs Disease Diagnosed?//**
 * Blood tests can be done to measure Hex-A levels
 * Prenatal diagnosis: Amniotic fluid testing (Cleveland Clinic)
 * Eye examinations done by doctors: a ‘cherry-red spot’ in the back of the individual’s eye is a result of the lipid storage, and is a tell-tale sign.


 * //What Kinds Of Solutions Are Available?//**

//Gene Therapy:// This method is geared toward utilizing “modified virus cells as vehicles to transport and duplicate Hex-A enzymes into the brain”. The Cure Tay-Sachs Foundation has raised over $400,000 to fund this type of therapy and is encouraged by the success from the first year of gene therapy research.

//Enzyme Replacement Therapy (ERT)// Hex-A has been produced in laboratories to replace or support the deficient enzymes. Although this method has been successful in other disorders with faulty lysosomal functions, it still presents problems crossing the blood brain barrier. (CTSF)

//Ganglioside (or Substrate) Inhibitors// The hope with this method is to create a balance inside cells by slowing the production of GM2 gangliosides so it matches the weakened rate of breakdown. (Platt) Clinical trials have yielded mixed results. (CTSF)

//Cord Blood Transplant// Umbilical Cord Blood Transplant is like a bone marrow transplant, however cord blood is less specific and can easily match the recipient’s marrow. To introduce the new blood, the existing blood stream has to be destroyed with chemotherapy or radiation. Then the new blood is introduced via IV. Recovery time can vary depending on type of medication or post-chemo or post-radiation organ damage. Survival rates are very low. (CTSF)

To date, Dakota Bihn, a young girl suffering from TSD, is the only child to survive a Cord Blood Transplant, which slowed the progression. Here are a few videos that tell her story:

media type="youtube" key="1nj7TdG5MfA?fs=1" height="293" width="360"

media type="youtube" key="WbUpMBHioT8?fs=1" height="291" width="359"

Although different treatments are becoming available and sometimes successful at slowing the progression of the disease, nothing has proved to be the cure for TSD. Tragically, for many cases, the only thing a family can is to enhance the quality of life for the sufferer, is to provide comfort and love.

In this video, Gavin is a young boy suffering from TSD. The second half of the video tells his story.

media type="youtube" key="a5JWQCBOMx4?fs=1" height="223" width="360"


 * Literature Cited**

Brain Briefings, //Society for Neuroscience//, February 2007, []

Cleveland Clinic. 1995-2010. []

CTSF – Cure Tay-Sachs Foundation. 2007. []

Human Diseases and Conditions. []

National Human Genome Research Institute. National Institute of Health. Updated June, 28, 2010. []

NTSAD – National Tay-Sachs & Allied Diseases Association, Inc. 2007. []

Platt, Frances M. and Butters, Terry D. 2000. Substrate deprivation: A new therapeutic approach for the glycosphingolipid lysosomal storage diseases. Expert Reviews in Molecular Medicine, 2, pp 1-17 doi:10.1017/S1462399400001484

Tay-Sachs Disease - Genetic Basis And Clinical Manifestations Of Tay-Sachs Disease. 2010. []

Tay-Sachs Disease Overview. Mayo Clinic. 2001-2010. []

“Tay-Sachs Disease Stem Cell Gene Enzyme Treatment” Wed, November 10, 2010 []