SRxA’s Word on Health is delighted to share news that could change the lives of the 500 or so children and families in the US, dealing with a rare and deadly disease. The breakthrough, announced this week in the online edition of Nature Medicine, suggests that scientists may have found a way to prevent and possibly reverse the most debilitating symptoms of ataxia telangiectasia (A-T) a rare, progressive childhood degenerative disease that leaves children, unable to walk, and in a wheelchair before they reach adolescence.
Karl Herrup, chair of the Department of Cell Biology and Neuroscience and his colleagues at Rutgers have discovered why this genetic disease attacks certain parts of the brain, including those that control movement coordination, equilibrium, muscle tone and speech.
When the team examined the brain tissue of young adults who died from A-T, they found a protein (HDAC4) in the nucleus of the nerve cell instead of in the cytoplasm where it belongs. When HDAC4 is in the cytoplasm it helps to prevent nerve cell degeneration; however, when it gets into the nucleus it attacks histones – the small proteins that coat and protect the DNA.
“What we found is a double-edged sword,” said Herrup. “While the HDAC4 protein protected a neuron’s function when it was in the cytoplasm, it was lethal in the nucleus.”
To prove this point, Rutgers’ scientists analyzed mice, genetically engineered with the defective protein found in children with A-T, as well as wild mice. The animals were tested on a rotating rod to measure their motor coordination. While the normal mice were able to stay on the rod without any problems for five to six minutes, the mutant mice fell off within 15 to 20 seconds.
However, after being treated with trichostation A (TSA), a chemical compound that inhibits the ability of HDAC4 to modify proteins, they found that the mutant mice were able to stay on the rotating rod without falling off – almost as long as the normal mice.
Although the behavioral symptoms and brain cell loss in the engineered mice are not as severe as in humans, all of the biochemical signs of cell stress were reversed and the motor skills improved dramatically in the mice treated with TSA. This outcome proves that brain cell function could be restored.
Neurological degeneration is not the only life-threatening effect associated with A-T. The disease, which occurs in an estimated 1 in 40,000 births, causes the immune system to break down and leaves children extremely susceptible to cancers such as leukemia or lymphoma. There is no known cure and most die in their teens or early 20s.
Herrup says although this discovery does not address all of the related medical conditions associated with the disease, saving existing brain cells and restoring life-altering neurological functions would make a tremendous improvement in the lives of these children.
“We can never replace cells that are lost,” said Herrup. “But what these mouse studies indicate is that we can take the cells that remain in the brains of these children and make them work better. This could improve the quality of life for these kids by unimaginable amounts.”
We certainly do. A cure cannot come soon enough.