UK Scientists repurposing old drugs – possible new treatments for Parkinson’s?

By bringing together cutting-edge stem cell technologies and computational biology, researchers at Oxford University have developed a unique way to identify existing drugs that could potentially be repurposed for treating Parkinson’s. This promising research, published in the journal Human Molecular Genetics, uses a stem cell technique to turn a small piece of skin from people with Parkinson’s into dopamine-producing brain cells – identical to those that are lost in Parkinson’s. Researchers then studied the patterns of gene activity in these Parkinson’s brain cells and compared them to those observed in the same brain cell types grown from people of a similar age without the condition. The team used a global database which holds information about the effects of thousands of different drugs, many which are already in clinical use, to look for ones that could normalize the gene activity of the Parkinson’s brain cells. They identified clioquinol – a drug which was first developed in the 1930s that is still used today in creams to treat skin infections. When taken orally, and over extended periods of time clioquinol can have serious side effects. Due to this, clioquinol as originally developed, is unlikely to be a future treatment for Parkinson’s. However, new drugs based on clioquinol may deliver the benefits without the risks.

Credit given to Professor Richard Wade-Martins, co-lead author on the study and head of the Oxford Parkinson’s disease Centre andThe team used a global database which holds information about the effects of thousands of different drugs, many which are already in clinical use, to look for ones that could normalise the gene activity of the Parkinson’s brain cells.

They identified clioquinol – a drug which was first developed in the 1930s that is still used today in creams to treat skin infections. When taken orally, and over extended periods of time clioquinol can have serious side effects. Due to this, clioquinol as originally developed, is unlikely to be a future treatment for Parkinson’s. However, new drugs based on clioquinol may deliver the benefits without the risks.

Professor Richard Wade-Martins, co-lead author on the study and head of the Oxford Parkinson’s Disease centre

 Dr. Caleb Webber, Investigator at the Parkinson’s UK funded Oxford Parkinson’s Disease Centre and co-lead author of the study.

Sources: https://www.parkinsons.org.uk/; mhttp://www.news-medical.net/news/20170119/New-way-of-repurposing-existing-drugs-could-unearth-promising-treatments-for-Parkinsone28099s-disease.aspx

A naturally-occurring compound has been found to block a molecular process thought to underlie Parkinson's disease, and to suppress its toxic products, scientists have reported. The findings, although only preliminary, suggest that the compound, called squalamine, could be exploited in various ways as the basis of a potential treatment for Parkinson's disease. The compound has previously been used in clinical trials for cancer and eye conditions in the United States, and a trial in Parkinson's disease patients is now being planned by one of the researchers involved in the study. Squalamine is a steroid which was discovered in the 1990s in dogfish sharks, although the form now used by scientists is a safer, synthetic analogue. To date, it has been extensively investigated as a potential anti-infective and anticancer therapy. But in the new study, researchers discovered that squalamine also dramatically inhibits the early formation of toxic aggregates of the protein alpha-synuclein - a process thought to start a chain reaction of molecular events eventually leading to Parkinson's disease. Remarkably, they also then found that it can suppress the toxicity of these poisonous particles. The researchers carried out a series of experiments which analyzed the interaction between squalamine, alpha-synuclein and lipid vesicles, building on earlier work from Cambridge scientists which showed the vital role that vesicles play in initiating the aggregation. They found that squalamine inhibits the aggregation of the protein by competing for binding sites on the surfaces of synthetic vesicles. By displacing the protein in this way, it significantly reduces the rate at which toxic particles form. Further tests, carried out with human neuronal cells, then revealed another key factor - that squalamine also suppresses the toxicity of these particles. Dr Michael Zasloff, professor of surgery and pediatrics at Georgetown University School of Medicine in the USA is Dr Michael Zasloff, professor of surgery and pediatrics at Georgetown University School of Medicine in the USAplanning a clinical trial with squalamine in Parkinson's Disease patients in the US.

Further research is, however, needed to determine what the precise benefits of squalamine would be - and what form any resulting drug might take. In particular, it is not yet clear whether squalamine can reach the specific regions of the brain where the main molecular processes determining Parkinson's disease take place but may be a huge building block on which to develop further treatments. The researchers suggest that it would be particularly interesting to start investigating the efficacy of squalamine as a means to alleviate certain symptoms and may be the target of study in the US. If taken orally, for instance, the compound may perhaps relieve the severe constipation many patients experience, by targeting the gastrointestinal system and affecting alpha-synuclein in the gut.

Sources: St John's College, University of Cambridge, UK; http://www.news-medical.net/news/20170117/Naturally-occurring-compound-can-inhibit-early-formation-of-toxins-linked-to-Parkinsons-Disease.aspxSource:

St John's College, University of Cambridge

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