T-A T-A to A-T?

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.

As regular readers of this blog know, A-T is a cause close to our hearts, and the courage of these children and their families inspire us daily.

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.”

A-T families are cautiously excited by the news. The A-T Children’s Project facebook page notes “This is certainly hopeful news, and we look forward to the results from further studies.”

We certainly do. A cure cannot come soon enough.

Pine Powder Puts an End to Sneezing

According to researchers at the University of Gothenburg, the end may be in sight for allergy sufferers.  Patients plagued by the misery of seasonal allergic rhinitis, better known as hay fever, can be cured, thanks to a powder derived from pine trees.

Cellulose nasal sprays like Nasaleze and Nasal Ease, have been on the market for years, but there wasn’t scientific evidence they worked – until now.

Now in this latest study, scientists found that the pine tree powder forms a barrier on the mucous membrane when puffed into the nose, filtering out allergens such as tree and flower pollen.

“The cellulose powder has no adverse effects, and this fact makes it a particularly attractive treatment for children,” said study author Dr. Nils Aberg, Associate Professor in the Department of Pediatrics.

The double blind, placebo-controlled  study, was carried out during the birch pollen season and involved 53 children and adolescents aged 8 – 18 years with allergies to pollen. Participants puffed the pine-tree derived cellulose powder in the nose three times daily for four weeks. They also took a daily dose of an oral antihistamine.
Pollen levels were measured every day and were subsequently analyzed in relation to the symptoms reported by the children. Patients or their parents were reminded to report their symptom scores using daily SMS messages sent to their mobile phones.
Results showed a statistically significant reduction in total symptom scores from the nose.  Further data for the study, published in Pediatric Allergy and Immunology, came from past unpublished statistics of pollen levels collected for 31 years at the same location in Gothenburg, from 1979 to 2009.

Dr. Aberg added: “We showed that the nasal symptoms of the children were significantly reduced in those who used the cellulose powder. The best effect was obtained at low to moderate concentrations of pollen”.

Word on Health asked leading allergist, Dr. Bill Storms for his reaction to this study.  He told us, “It appears that the  waxy coat of the pine tree pollen might line the inside of the nose after sniffing it and  this might prevent other pollens from getting into the mucus membranes. However, I note that patients were asked to do this three times a day and I’m not sure how many will do this.  I also wonder if there are any long term effects of putting cellulose in the nose.”

As we’ve said so many times before, further studies are needed.