Existing cancer medication offers potential to treat Huntington's disease

December 06, 2017

A drug already used to treat certain forms of cancer may also be an effective therapy for Huntington's disease, according to a new study in the latest issue of Science Translational Medicine. The same study also increases our understanding of how this drug, and other medications like it, may offer hope for other neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease.

Huntington's disease is a devastating, inevitably fatal disease, with no medications that slow or stop disease progression. In this study, mice with the equivalent of Huntington's disease became more mobile, recovered from neurodegeneration, and lived longer after being treated with bexarotene. The same research builds on a 2016 study where La Spada and his team showed that the drug KD3010 is an effective treatment for Huntington's disease in mice and in human patient neurons made from stem cells.

Senior author Al La Spada, MD, PhD, (photo) said the study results are exciting not just because these drugs worked, but because of how they worked. "It's not just the response from the drugs, but the mechanistic pathways these drugs are targeting," said La Spada, director of the forthcoming Duke Center for Neurodegeneration and Neurotherapeutics. "These pathways are relevant to other neurodegenerative disorders and potentially the aging process, itself in addition to Huntington's disease."

Bexarotene and KD3010 function by activating PPARδ, a transcription factor that keeps neurons functional in two ways: by keeping mitochondria healthy and active, and by helping neurons remove dysfunctional proteins. Mice--and humans--with Huntington's disease have problems activating PPARδ. When La Spada and colleagues treated Huntington's mice with bexarotene or KD3010, they observed improved mitochondrial health in neurons, as well as increased removal of damaging misfolded proteins.

The same factors of impaired mitochondrial function and protein misfolding are recognized as increasingly important in diseases like Alzheimer's disease, Parkinson's disease, and ALS.

The study doesn't mean that patients with Huntington's disease or other conditions should rush to get bexarotene or KD3010. Further research needs to determine how to use these drugs in human patients. Bexarotene can have difficult side effects at high dosages, and optimal doses aren't known, while KD3010 has only been tested in human subjects for type II diabetes.

Instead, future therapies for Huntington's disease and other neurodegenerative conditions may take a cue from HIV treatments and involve a "cocktail" approach of combined medications. Lead author Audrey Dickey, PhD, found that, taken together, bexarotene and KD3010 produced better results in cells even when given at lower doses.

"With this approach, we could minimize side effects with lower doses of each compound, even when together the treatments provide a higher effect than either one alone," said Dickey. "We are carrying out further research on the underlying mechanisms of neuroprotection and applying this research to other diseases with similar issues of mitochondrial dysfunction and protein quality control, such as Parkinson's disease, Alzheimer's disease, and ALS."
-end-
The article was written by La Spada, Dickey, and colleagues at the Duke Department of Neurobiology, University of California San Diego, the Salk Institute for Biological Sciences, and the Johns Hopkins School of Medicine. It is available online here.

Duke Department of Neurology

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.