As promising as a drug candidate may be, the unfortunate truth is that not all of them end up performing as hoped – but that doesn't mean they're completely useless. Researchers at Oxford University have managed to give second life to an experimental cancer drug known as tasquinimod, which has now shown promise in preventing Parkinson's.
Tasquinimod emerged as a promising drug in fighting solid tumors, with most research focusing on using it to treat prostate cancer. The drug made it through to phase three clinical trials, but unfortunately it didn't seem to extend overall survival rates in patients, and after those disappointing results development was discontinued for prostate cancer treatment.
But the work wasn't for nothing – the clinical trials so far have shown that tasquinimod is well tolerated by the body, and it could still potentially help treat other illnesses, such as Parkinson's disease.
To investigate the drug, the Oxford team first took skin cells from patients with a rare genetic form of Parkinson's, and turned them into a type of stem cell known as induced pluripotent stem cells (iPS). From these the researchers grew brain cells in vitro, allowing them to observe progression of the disease in the lab.
The team found that the key may be an error with a protein known as HDAC4. When that happens, this protein begins to repress certain genes, which in turn messes with the brain cells' ability to regulate the natural cycle of proteins. That means those proteins build up in the cells, which has long been known to contribute to Parkinson's and related neurodegenerative diseases like Alzheimer's.
Tasquinimod comes to the rescue by blocking HDAC4, meaning those key genes aren't "switched off," and effectively halting progression of the disease.
"We think that switching off these genes in brain cells may play a vital role in the cell damage and death that occurs in Parkinson's," says Richard Wade-Martins, co-lead author of the study. "Finding a way to 'turn them back on' with a drug could be a promising, unexplored way to develop new treatments."
The researchers then repeated the study using iPS cells gathered from people with the more common non-genetic form of Parkinson's, and found that the same pattern of inactive genes seems to be at play. That indicates that these people might also benefit from the treatment, although the team also acknowledges that some people don't seem to respond to it.
"The study also highlights the growing number of drugs which can be repurposed from their original medical use to treat Parkinson's," says David Dexter, Deputy Director of Research at Parkinson's UK, which funded the study. "Developing a drug from scratch is a long, slow and expensive process. By finding existing drugs and moving them rapidly into clinical trials, we can make them available for people with Parkinson's much more quickly, easily and cheaply."
Although that process may be streamlined, it is still early days for tasquinimod. The study has only been conducted on a total of 10 patients so far, so more testing will need to be done before it could become a viable treatment option.
The research was published in the journal Cell Stem Cell.
Source: Oxford University
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