Study of mice suggests babies with Tay-Sachs relief
Removal of brain protein could alleviate some symptoms, extend life for affected children.
By JUDY SIEGEL-ITZKOVICHSULEIMAN IGDOURA 370(photo credit: McMaster University)
Tay-Sachs disease, the degenerative and always fatal neurological genetic disease that is most commonly carried by Ashkenazi Jews, has been recognized even by ultra-Orthodox rabbis as a legitimate reason for the abortion of an affected fetus. But readily available drugs called tumor necrosis factor agents may have a “dramatic effect” on children with this condition, according to scientists at McMaster University near Toronto.“There is hope for this disease,” says biology Prof. Suleiman Igdoura, lead researcher of the study. “Imagine what that could mean for parents who have a child diagnosed with this incurable condition, who may have only a few years with their child.”Tay-Sachs is a genetic disorder caused by the absence of vital enzymes that are involved in the breakdown of waste within cells.The rare autosomal recessive genetic disorder is also known as GM2 gangliosidosis or hexosaminidase A deficiency. Without these enzymes, waste accumulates and eventually destroys healthy cells, leading to paralysis, blindness, mental retardation and eventually death.The defective gene has been carried mostly among Ashkenazi Jews, but a different mutation affects isolated non-Jewish French Canadians and Cajun people in Louisiana.Igdoura and his team have found that when a key protein in the brain known as TNFa is removed, some of the devastating symptoms of Tay-Sachs and a similar disease called Sandhoff were much less severe when tested in mice. Those symptoms include spasms, muscle wasting and loss of neurological function.The findings are significant because the protein can be managed by FDA-approved drugs, readily available on the market, said Igdoura.“With Tay-Sachs and Sandhoff, we have very little to offer families in terms of therapeutics to help their children,” said Igdoura, whose article was just published in Human Molecular Genetics.“These are orphan diseases where there are not many medications available. But we feel this is a significant step in improving quality of life and quite possibly extending lives,” the Canadian biologist said.Prof. Ephrat Levy-Lahad, head of the medical genetics institute at Jerusalem’s Shaare Zedek Medical Center, told The Jerusalem Post that the number of babies actually born in Israel with Tay- Sachs is very, very small because of pre-marital and other testing.
Most Tay-Sachs babies born in the world are not Jewish. But when it happens, it is devastating to the family, she said, as they usually die by the age of four or five after great suffering.“The advantage is that TNF inhibitors already exist and are used on various patients. If this use pans out, it will be a new pathway and be easier to research,” said Levy-Lahad.“It’s gratifying that researchers haven’t given up studying Tay- Sachs, even though there are few cases because of genetic testing.But if the TNF agents do nothing to protect the Tay-Sachs baby’s brain and lungs, giving the medication would just prolong its suffering. We wouldn’t recommend not doing termination of a pregnancy; it’s still a clear indication for abortion. Avoiding such pregnancies are most effective.”“There are distinct stages within the disease, so we wanted to find targets we could interfere with, to delay the terrible outcome or halt it altogether,” explained Igdoura.Using mice that were genetically altered to mimic Tay-Sachs and Sandhoff, researchers found levels of TNFa rose significantly during the early stages of the diseases.But when TNFa was subsequently removed, there was a significant improvement in the lifespan of the mice and neurological function.“We also found that neurons didn’t die as early as they do with the disease, so we delayed the progression as well,” continued Igdoura.“We have identified a molecule that is the culprit and we believe there are drugs available to stop it,” he said.
