New Therapeutic Treatment Discovered for Huntington's Disease

A recent study looks a a new target therapy for Huntington's disease.

This genetic disorder that affects roughly one in 10,000 individuals from 35 and up can lead to increasingly severe problems, often involving mental and behavioral disorders. And unfortunately, many patients who suffer from this health issue will die as there is no current treatment to modify its progression. 

Study authnors Michal Mielcarek, Gillian Bates and colleagues at King's College London looked at how the enzymes one of the enzymes as a target that could provide a possible new treatment. For instance, the new study looks at an enzyme involved in the process and how the classlic role transcription of HDAC4 benefits the health issue. (Humans have eleven different HDAC enzymes, according to background infroamtion from the study.

The study notes the following regarding the enzyme, courtesy of a press release: "The researchers noted that the HDAC4 protein naturally contains a region that, like mutant huntingtin, is rich in the amino acid glutamine. They show that HDAC4 can associate directly with huntingtin protein in a manner that depends on the length of the glutamine tracts, but that this association between HDAC4 and huntingtin occurs in the cytoplasm of nerve cells in the mouse brain, and - surprisingly - not in the nucleus, where HDAC4 is known to have its transcriptional role.

"Bates and colleagues did their work in an aggressive disease mouse model of Huntington's disease - the gold standard model for this type of study. They find that halving the levels of HDAC4 in the cells of Huntington's disease mice can delay the aggregation of huntingtin in the cytoplasm, thereby identifying a new route to modulating the toxicity of mutant huntingtin protein. Crucially, reducing HDAC4 levels can also rescue the overall function of nerve cells and their synapses, with corresponding improvements seen in coordination of movement, neurological performance and lifespan of the mice. In agreement with the cytoplasmic association between HDAC4 and huntingtin, this all happens without any obvious improvement in the defective gene transcription in the nucleus.

"There are currently no disease-modifying therapeutics available for Huntington's disease. It is still very early days and it is important to note that the medical applications of any therapy arising from this study have not been studied in a clinical setting and are far from clear. However, one broad-brush HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) had previously been shown to improve movement defects in preclinical tests in this mouse model. The authors have shown in a related publication that, in addition to inhibiting HDAC enzyme function, SAHA decreases levels of the HDAC4 protein. Therefore it is hoped that the development of HDAC4-targeted compounds may be a promising strategy in improving the lot of Huntington's disease patients."

More information regarding the study can be found via the journal PLOS Biology.