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.

Bitter Sweet News for Asthma Sufferers!

In a discovery that could potentially transform asthma treatment, researchers from Maryland have found our lungs carry receptors for bitter tastes.

The study, just published in Nature Medicine, found that receptors in the lung are the same as those that cluster together as taste-buds on our tongue.  In experiments using human and mouse lung tissue and mice with asthma, they found stimulating these receptors in the lungs with bitter substances  opened the airway more extensively than any known drug currently available for the treatment of asthma or chronic obstructive pulmonary disease.

These results came as a surprise to the scientists, who had expected bitter substances to constrict the airways rather than open them.

I initially thought the bitter-taste receptors in the lungs would prompt a ‘fight or flight’ response to a noxious inhalant, causing chest tightness and coughing so you would leave the toxic environment, but that’s not what we found,” said lead researcher Dr Stephen Liggett.

In their experiments, the researchers tested bitter compounds such as quinine and chloroquine substances commonly used  to treat malaria.  However, there are thousands of other non-toxic, bitter compounds that are known to activate these receptors including natural plant substances and some synthetic agents.

Sadly for the campari, citrus and bitter chocolate lovers among us, the researchers did not find any link between eating bitter foods and improved breathing.  “Based on our research, we think that the best drugs would be chemical modifications of bitter compounds, which would be aerosolized and then inhaled into the lungs with an inhaler,” Liggett said.

Even then, inhaled therapies may not be available for years.

SRxA’s Word on Health will continue to follow this story and bring you all the latest developments.  In the meantime, if you want to spread the word about currently approved asthma treatments, please contact us to learn more about how our world class teams of Clinical Advisors can help.

“Ouchless” Flu Vaccine

Instead of getting a BandAid after your flu shot, a new delivery patch could actually allow people to receive their vaccine this way.

The patches contain hundreds of tiny little needles, so small you don’t even feel them, that dissolve into the skin and release the vaccine. The result –  simplified immunization programs. By eliminating the use of needles and syringes, three of the biggest problems simply disappear.

  • fear of needles
  • disposal of leftover needles and syringes
  • the need for trained medical personnel

The microneedle patches are applied like a BandAid and could allow self-administration of vaccine during pandemics as well as in schools and assisted-living facilities.  They could also simplify large-scale immunization programs in developing nations.

Researchers led by Professor Mark Prausnitz of Georgia Institute of Technology reported their research on microneedles in Sunday’s edition of Nature Medicine.

The business side of the patch apparently feels like fine sandpaper. In tests,  people rated the discomfort at 1/10th – 1/20th that of getting a standard injection. In other words, nearly everyone said it was painless.

The patch, which has been tested on mice, was developed in collaboration by researchers at Georgia Tech and Emory University. The work was supported by the National Institute of Health. The researchers are now seeking funds to begin tests in people and, if all goes well, the patch could be in use in five years.

Flu vaccination is recommended for nearly everyone, every year. According to Prausnitz, “Many people don’t get the shot because it’s inconvenient, but if they could get it in the mail or at the pharmacy they might do so.” The patch is placed on the skin and left for 5  to 15 minutes although it can remain longer without doing any damage.

Asked if the term “microneedle” might still frighten some folks averse to shots, Prausnitz said he was confident that marketers would come up with a better term before any sales began.

SRxA’s Word on Health challenges you to come up with some creative ideas.