Huntington’s Treatment Blog

UT Southwestern Medical Center researchers have found that a drug used in some countries to treat the symptoms of Huntington’s disease actually prevents the death of brain cells in mice genetically engineered to mimic the hereditary condition.

The research sheds light on the biochemical mechanisms involved in the disease and suggests new avenues of study for preventing brain-cell death in at-risk people before symptoms appear - making the drug more important than people originally thought.

The drug, called tetrabenazine (TBZ), is commercially distributed as Xenazine or Nitoman and blocks the action of dopamine, a compound that some nerve cells use to signal others. TBZ is approved for use in several countries, but is still awaiting FDA approval in the US. It is used to treat uncontrollable muscle movements in Huntington’s and other neurological conditions.

In the study, the UT Southwestern researchers used mice that were genetically engineered to carry the mutant human gene for Huntington’s, causing symptoms and death of brain cells similar to those seen in the disease. The study focused on an area of the brain called the striatum, which plays a critical role in relaying signals concerning motion and higher thought and receives signals from several brain regions.

The striatum is primarily made up of nerve cells called medium spiny neurons, which undergo widespread death in Huntington’s. One major input to the striatum comes from an area called the substantia nigra, which controls voluntary movements and sends signals to the striatum via nerve cells that release dopamine.

The researchers conducted various coordination tests on both normal and genetically manipulated mice. Engineered mice given a drug that increased brain dopamine levels performed worse on these tasks, while TBZ protected against this effect. Most importantly, TBZ appears to reduce significantly cell loss in the striatum of the engineered mice, the scientists report.
The work was supported by the Robert A. Welch Foundation, the Huntington’s Disease Society of America, the Hereditary Disease Foundation, the HighQ Foundation and the National Institute of Neurological Disorders and Stroke.

For further (important) information, please read this page by Dr. LaVonne Veatch Goodman at the HD Drug Works site.

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St Andrews University (Fife) biologists claim to have moved a step closer to finding a cure for Alzheimer’s disease, in developing a compound which has successfully prevented the disease killing brain cells. It also appears to improve memory and learning ability that is already damaged.

Working with American researchers they developed man-made compounds capable of blocking a nerve cell interaction known to lead to the symptoms of the disease. The results of the study - carried out in the laboratory using a model of the disease - have prompted the Alzheimer’s Research Trust to help fund a further three years research.

A drug that can stop Alzheimer’s disease from killing brain cells is a holy grail for researchers working to overcome the devastating condition which affects more than 500,000 people in the UK alone. The number of sufferers is expected to double to more than one million with the general ageing of the population over the next generation.

Alzheimer’s is linked to the build-up of amyloid protein, which eventually forms “senile plaques”. The amyloid protein inflicts damage by interacting with an enzyme called amyloid beta alcohol dehydrogenase (ABAD) and releasing toxic substances which kill brain cells.

Researchers at St Andrews University initially focused on developing the three-dimensional shape of ABAD and understanding how amyloid attaches itself to the structure.

Dr Frank Gunn-Moore, senior lecturer at the university’s school of biology, said: “Alzheimer’s sufferers produce too much amyloid and ABAD in their brains. Based on our knowledge of ABAD, we produced an inhibitor that can prevent amyloid attaching to it in a living model.”

Dr Gunn-Moore, who led the research, added: “We have shown that it is possible to reverse some of the signs associated with Alzheimer’s disease. The work is now being continued to try and refine the inhibitor into a potential drug. Our research holds a possible key for the treatment of Alzheimer’s disease, particularly in its early stages.”

Dr Susanne Sorensen, head of research with the Alzheimer’s Society, said: “The study provides another important piece in the puzzle for understanding Alzheimer’s disease and points toward a possible new treatment target, which has so far been unexplored.”

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New insights into how bacteria form fibers called curli offer intriguing clues to the formation of harmful protein tangles in diseases such as Alzheimer’s, Huntington’s and Parkinson’s, University of Michigan researchers report.

The research builds on a chance discovery that U-M microbiologist Matthew Chapman and co-workers made five years ago. In research initially aimed at understanding urinary tract infections, they discovered that the common bacterium Escherichia coli makes and employs amyloid fibers, the same types of fibers that are the calling cards of many neurodegenerative diseases. Until then, amyloids were considered “biological blunders” that occurred only when proteins misfolded into deviant forms that aggregate into harmful clumps, Chapman said. But his work showed that bacteria produce amyloid fibers “by design” and use them to adhere to surfaces and to interact with other bacteria.

You can read the full article on ScienceDaily.

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Researchers at the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) have identified a potential new drug target for the treatment of Parkinson’s disease and possibly for other degenerative neurological disorders.

In an upcoming issue of the journal Science, the investigators describe finding, in cellular and animal models, that blocking the action of an enzyme called SIRT2 can protect the neurons damaged in Parkinson’s disease from the toxic effects of alpha-synuclein, a protein that accumulates in the brains of Parkinson’s patients. The study, which also suggests that inhibiting this pathway could help in the treatment of other conditions in which abnormal proteins accumulate in the brain, is receiving early online release on the Science Express website at http://www.sciencexpress.org.

The researchers plan to study the effect of the new inhibitor AGK2 in models of HD.

The full press release, along with editorial comments, can be found on the HD Lighthouse website.

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Important research reported in May 2007 Nature Magazine shows that Huntington’s turns a normally protective enzyme into one that likely accelerates disease progression. Dr. Cynthia McMurray and colleagues show that OGG1, an enzyme that normally repairs damaged DNA, seriously malfunctions and causes a further increase in the already enlarged CAG repeat number in HD brain cells.

Dr. Goodman believes the real and practical “take home” message from this important study is that HD people may now have two good reasons to take Creatine.

Read the full article on the HD Drug Works site.

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Mice carrying the genetic mutation that causes Huntington’s Disease (HD) showed marked improvements in alertness and their ability to learn after they were given drugs that put them to sleep.

Researchers at the University of Cambridge found that daily treatments of Alprazolam or chloral hydrate, two different sedative drugs, enabled them to develop a regular sleep pattern and improved their cognitive function – their ability to understand and act on information.

According to the Cambridge neuroscientists conducting the research, HD mice have abnormal circadian rhythms; their daily sleeping and waking cycles are disrupted and irregular. Since sleep disruption contributes to problems with perception and learning in healthy people, the team wondered whether the circadian disruption and cognitive disturbances in HD mice were linked.

Read the rest

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