Novel protein might protect against Huntington’s disease: Study shows that deleting Rhes significantly decreases problems associated with behavior in diseased animal models.

Researchers from the Florida campus of The Scripps Research Institute (TSRI) have conclusively established the pivotal role of an activating protein, Rhes (Ras homology enriched in striatum), in focusing the toxicity of Huntington’s disease within the striatum (small section of the forebrain controlling body movements and cognitive processes). The study was published in the journal Neurobiology of Disease.

Protect Against Huntington’s Disease

Huntington’s disease specifically affects the area of the brain involved in controlling movement – potentially destroying nerve cells with a bombardment of toxicity. “Our study definitively confirms the role of Rhes in Huntington’s disease,” said Assistant Professor Srinivasa Subramaniam at TSRI, who led the study. “Our next step should be to develop drugs that inhibit its action.”

In a study performed earlier, Subramaniam and his colleagues demonstrated that Rhes could bind to a sequence of repeats in the Huntington’s protein (a protein associated with the disease). This results in increased damage and death of nerve cells. The present study shows that deleting Rhes significantly decreases problems associated with behavior in diseased animal models.

Moreover, it was also seen that injecting Rhes into the cerebellum (a region not affected by Huntington’s toxicity) of these animals resulted in exacerbation of motor functions, such as balance and coordination. Lesions and damaged nerve cells were also found in the cerebellum, confirming the toxic and deleterious effects of Rhes protein even in areas impervious to damage by Huntington’s disease.

“Perhaps the biggest question to emerge from this study is whether Rhes is a good drug target for Huntington’s disease,” said Subramaniam. “The short answer is ‘yes.’ Drugs that disrupt Rhes could alleviate Huntington’s pathology and motor symptoms.”

Supriya Swarnkar, first author and a part of Subramaniam’s lab, said, “Many Huntington’s disease patients experience psychiatric-related problems, such as depression and anxiety. But it’s unclear whether they are the cause or consequences of the disease. We think, by targeting Rhes, we might block the initiation of Huntington’s, which we predict would afford protection against psychiatric-related problems as well.”