Story URL: http://news.medill.northwestern.edu/chicago/news.aspx?id=164436
Story Retrieval Date: 9/21/2014 1:05:17 AM CST
U.S. Air Force photo/Master Sgt. Maurice Hessel
Tay-Sachs is a result of not enough hexosaminidase-A, also known as Hex-A, an enzyme produced by the Hex-A gene.
With Tay-Sachs, the gene is abnormal and because of this the cells do not produce this certain type of enzyme. This enzyme, Hex-A, is needed to break down a particular kind of fat substance known as ganglioside GM2, said Dr. Joel Charrow, a genetics specialist at Children’s Memorial Hospital and professor at Northwestern University Feinberg School of Medicine.
“It’s not the kind of fat that you eat, so you can’t affect it by diet,” he said.
“It’s something the body makes and the body needs, but the body also needs to be able to control and to regulate the amount of GM2 in the cells and to be able to break it down as well,” he said.
The gangliosomes GM2 accumulates in the cells, “the most devastating effect is the accumulation of the GM2 in the nerves of the brain,” Charrow said.
It’s not entirely understood how the accumulation of the GM2 in the nerves of the brain causes neurological problems. What is understood is that the cells become stuffed with the GM2 and don’t function properly, Charrow said.
There are three forms of Tay Sachs: infantile, juvenile, and late-onset.
“The infantile version usually hits kids at birth or even before birth and those kids live to be 3 to 5 years old, and they usually have no Hex-A or very very low levels of Hex,” said Kenneth Bihn, the president of Cleveland-based Cure Tay-Sachs Foundation. Symptoms can vary but include slow development and a loss of peripheral vision. By the age of two, most children have seizures and diminishing mental function. As time progresses the infant will lose his or her ability to sit up, turn over, crawl, sit, or even reach out.
The most rare form of Tay-Sachs is juvenile Tay-Sachs, these children have enough Hex-A to clear some of the GM2 in their brains but not enough to sustain life, and the children diagnosed with this type of Tay-Sachs may live, at most, to be 15-years-old, Bihn said. Symptoms vary but include lack of coordination, slurred speech, tremors, and sometimes the child will develop mental illness.
The late onset form of Tay-Sachs is typically diagnosed in adolescents.It has recently been recognized as a rare form of Tay-Sachs and the details of this type of Tay-Sachs are not completely known, according to the National Tay-Sachs & Allied Diseases Association website. The symptoms for late onset form of Tay-Sachs include slurred speech, tremors and lack of coordination.Adolescents who are diagnosed with this form of Tay-Sachs are often misdiagnosed.
Tay-Sachs disease is always fatal.
As Tay-Sachs disease – a deadly genetic disease– becomes more rare among the human population, more research, instead of less, is being done to find a cure.
“We decided we’ve got to fight bigger, so we started this foundation to raise money to support research for Tay-Sachs,” said Kenneth Bihn, the president of the Cleveland-based Cure Tay-Sachs Foundation and the father of a Tay-Sachs child.
Cases of Tay-Sachs, a lysosomal storage disease affecting tiny organs in cells that store enzymes, are in decline. Last year about 11 children were diagnosed with the disease compared to the 100 per year that were diagnosed before prenatal testing began, according to a report in the April 16 issue of Science magazine.
“Theoretically it makes sense that you’d rather cure breast cancer because that effects millions of women and this effects 15-to-20 kids, so that makes sense from a societal standpoint. But I would say as a parent, who has a child who has the disease – it’s always fatal, it always has been fatal – let’s cure it,” he said.
Despite the decline, research on Tay-Sachs has not slowed down, according to Dr. Joel Charrow, a genetics specialist at Children’s Memorial Hospital and professor at Northwestern University Feinberg School of Medicine.
“I think there is continued interest in lysosomal storage diseases; Tay-Sachs and others that affect the brain, and research continues in that area,” Charrow said.
There are three ways scientists and researchers have conceived to treat this condition, he said.
The first approach is to use gene therapy and replace the gene with a working copy of it that would produce the right enzyme to break down the fat that is obstructing the nerve cells in the brain.
“The only way they’ve done this is in cells that circulate in the blood,” he said. “And there are a couple approaches that have been taken to get genes into other types of cells.”
One method is to infect a patient with a gene-packaged virus that would go to the brain and introduce the gene into brain cells that way.
“Potentially this is a lot riskier. This may be the more promising research, but it is also the type of research that has to be conducted extremely carefully,” Charrow said.
The second approach could use enzyme replacement therapy. This type of therapy is currently being used to treat a number of other lysosomal storage diseases.
“But none of the diseases which there are currently enzyme replacement therapies have significant brain involvement,” Charrow said. “And this is where the problem pertaining to curing Tay-Sachs lies. There is a significant amount of brain involvement when it comes to Tay-Sachs."
The other predicament with the brain is the blood-brain barrier, which prevents large molecules from passing into the brain, he said.
“People have labored for about 40 years to find out how to get things passed that barrier. There has been some progress in understanding the blood brain barrier and finding ways to sneak things across it, but that research is at a pretty basic level," Charrow said.
The third potential approach to curing Tay-Sachs is finding drugs that can decrease the rate of production of ganglioside GM2, a fatty substance that accumulates in the brain of Tay-Sachs patients.
“The idea would be to decrease the rate of GM2 so that there would be less accumulation. And people are working on that in animal models and in tissue cultures,” Charrow said.
Research for a cure also involves money. The National Institute of Health recently granted $3.5 million to the Tay-Sachs Gene Therapy Consortium, which will conduct the first comprehensive Tay-Sachs Natural History study, according to Susan Kahn, the executive director of the National Tay-Sachs & Allied Diseases Association. The study will be instrumental in designing a future clinical trial.
“There’s a lot going on and it’s not specifically for Tay-Sachs disease but for very closely related conditions in which the technology should be transferrable from one disease to the other,” Charrow said. There are about 40 other lysosomal storage diseases.
Bihn agreed, “Theoretically, if we can cure one neurological disease that’s going to have serious ramifications on other neurological diseases.”