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An anti-cancer drug treats Huntington's disease in mice


View:22 Time:2017-12-07


As well age, we tend to develop age-related diseases and health conditions. One group of diseases strongly linked to age are neurodegenerative diseases, which are progressive, debilitating and largely untreatable conditions that destroy neurons. Because the world population is aging rapidly, the number of people with neurodegenerative diseases will also increase, and this will place a big burden on health systems and budgets. The current treatment options for neurodegenerative diseases only treat the symptoms but do not address the cause.

Researchers studying neurodegenerative diseases have now found a novel potential treatment for Huntington's disease (HD), a form of neurodegenerative disease that impairs a person's physical and mental abilities. The study has shown that an anti-cancer drug called bexarotene could treat HD in cellular models of HD as well as in an HD mouse model. Furthermore, the study has provided clearer insights into how bexarotene works. These discoveries will have implications for treatment of not only HD but also other forms of neurodegenerative diseases.

A growing body of evidence suggests that PPARδ, a transcription factor highly expressed in many tissues, is repressed in HD and is required for normal neuronal function, and that boosting PPARδ may block neurodegeneration in HD. Therefore, activation of PPARδ represents a potential therapeutic strategy for HD.

Dr. Albert La Spada, who is a professor at the University of California, has been studying HD for years. Previously, Dr. La Spada and his team demonstrated in mouse models of HD that "pharmacologic activation of PPARδ, using the agonist KD3010, improved motor function, reduced neurodegeneration, and increased survival."

In the new study, Dr. La Spada and his team tested the effect of bexarotene, an FDA-approved drug that is used to treat cancer and seems to promote PPARδ activation. Using cellular models of HD, they found that bexarotene was neuroprotective. Using a mouse model of HD, they discovered that like KD3010, bexarotene improved motor function, reduced neurodegeneration, and increased survival. Further investigation provided insights into the working mechanisms of bexarotene: the drug activated PPARδ to improve mitochondrial function and cellular quality control.

In summary, the results highlight the therapeutic potential of bexarotene for HD. Future research will focus on determining the dosage, safety, and efficacy of bexarotene as a treatment option for patients with HD.

The study is carried out by Dr. La Spada's team in collaboration with researchers from Salk Institute for Biological Studies, Johns Hopkins University School of Medicine, and Duke University Medical Center. You can read the full paper (PPARδ activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis) in the journal Science Translational Medicine.

There is also evidence that bexarotene may reverse memory problems in a mouse model of Alzheimer's disease, suggesting that the drug may have implications for treatment of other neurodegenerative diseases.

CusAb -- a manufacturer of proteins and antibodies -- offers PPARδ recombinant protein, PPARδ monoclonal antibody, and PPARδ polyclonal antibody for research.
 
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