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Cellular Protection Mechanism To Halt Parkinsonís

by Gopalan on December 27, 2011 at 9:58 PM
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 Cellular Protection Mechanism To Halt Parkinsonís

A novel therapy for Parkinson's disease seeks to make use of the way the mitochondria is protected from common viruses.

The research at the University of Cambridge, published this week in the Journal of Experimental Medicine, involved molecular virologists working in collaboration with neuroscientists to share their expertise across disciplines.


Current treatments for Parkinson's centre on symptomatic drugs which help treat some of the motor features of the disease, but they are not able to stop it from progressing. Indeed, over time these drugs can produce their own side-effects.

The novel methodology developed by the Cambridge researchers stemmed from the work of Professor John Sinclair and colleagues at the Department of Medicine in studying the ways in which common viruses - such as herpes - seek to survive and replicate in cells in the body. When these viruses invade a cell, a tiny component of the virus called the Beta2.7 gene guards the mitochondria from damage for an interval of time - typically five days - so that the virus can replicate and spread from cell to cell.

In looking at how the virus gene functions, Professor Sinclair spotted the potential for harnessing this protective function to help cells survive attack by neurological disorders. The component of the virus that protects the cells' mitochondria is a section of RNA (ribonucleic acid) which, like DNA, is essential for life. The molecular virologists led by Professor Sinclair used a method of complexing (mixing) the RNA derived from a human cytomegalovirus to a protein of a rabies virus. This protein was selected as it enables the beta2.7 to cross into the brain when the whole complex is given into the circulation, and, as only of a portion of the rabies and herpes viruses are used, there is no danger of contracting any disease from either virus.

Having identified the potential offered by the virus as an agent for 'search and rescue', Professor Sinclair collaborated with Professor Roger Barker and colleagues at the Cambridge Centre for Brain Repair to see whether this novel protein/RNA complex could protect neurons from cell death associated with PD. Using rat models, the results have been promising and resulted in a further tranche of research funding from the Michael J Fox Foundation to take work in the laboratory forward to help develop the novel therapeutic for eventual clinical use.

The researchers emphasise that much work remains to be done in taking the therapy to the point at which clinical trials can be undertaken. "Our results with rat models are tremendously encouraging, but we need to do a lot more in terms of refining and optimising the therapy before it could be used in patients. For example, we don't know what the dosages or frequency of treatment might need to be in treating humans," said Professor Sinclair.

"What we have established is proof of principle - essentially showing that this is a truly novel and highly promising pathway for treating not just the dopamine cell loss in Parkinson's but also all cell losses in this condition, as well as other chronic neurodegenerative disorders."

The novel therapy offers a number of significant advantages over all currently used surgical and drug therapies. Professor Barker explained: "In many ways the therapy we've developed is a beautiful treatment. It can be delivered through an injection direct into the bloodstream, for example into the arm of the patient. This makes it much easier to use than many other putative disease-modifying therapies such as growth factors which have to be injected directly into the brain. This new agent also appears to be non-immunogenic - in other words it does not trigger an immune response so it can be used repeatedly and should still maintain its potency. Finally, it appears to go only into the brain and nowhere else in the body and then to target only cells that are unwell."

The next stage of the research will be to test the novel therapy in other models of Parkinson's to help define the dosage and time course of delivery.

The researchers' work in harnessing the behaviour of viruses may have wider applications for the treatment of other neurodegenerative diseases - including Alzheimer's and Huntington's diseases.

Source: Medindia

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