Urgent call for new drugs to treat causes of Parkinson’s

Deryal Wood

Deryal Wood was 45 when she first began to suffer tremors in her hands. Her symptoms slowly worsened and she was diagnosed nine years ago as having early onset Parkinson’s disease. “I was given the drug L-dopa. The tremors disappeared,” she said.

But the tremors returned a few years later and doctors had to increase her dosage. “The side effects became horrible. My legs would freeze and I would fall over. I would suffer terrible muscle cramps every couple of hours,” said Wood, who lives with husband David and daughter Fay in Bexley, Kent.

As Wood’s symptoms worsened, she was offered treatment called deep brain stimulation, which involves placing electrodes deep into a patient’s brain. That has brought her tremors and movements back under control so that she can lead a fairly normal life.

“However, it does not control the depression, insomnia or exhaustion that I also experience because of Parkinson’s. Patients like me want something that slows down or halts the degeneration in our brain cells and so stops the disease,” she said.

It is a view shared by a rising number of doctors and scientists who believe action needs to be taken to discover a new class of drugs to tackle the degenerative nerve ailment.

Current medicines treat only the symptoms, they say, and should be supplemented with agents that directly attack its underlying cause.

To date, these efforts have failed, despite intense efforts by pharmaceutical companies which have spent billions on the quest.

“Drug companies have produced absolutely nothing to help with the degenerative process of Parkinson’s over the past two decades,” said Dr Tom Foltynie, at University College London’s Institute of Neurology. “We desperately need to take a new approach.”

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Foltynie was speaking last week as scientists marked the 50th anniversary of the first use of levodopa, perhaps better known as L-dopa, the most effective drug ever created to treat Parkinson’s. It can extend patients’ quality of life for years, but eventually loses its effectiveness, as it has with Wood.

About 130,000 people in Britain are affected by Parkinson’s disease, which is caused when brain cells, which make a chemical messenger called dopamine, start to die. As a result, messages between brain cells become disrupted and patients’ movements are disturbed.

Some suffer from rigidity of stance, others develop tremors. Later they can develop dementia, anxiety and depression. L-dopa can mask the development of some of these symptoms – particularly those that  affect movement – but only for a few years. Slowly the tremors and rigidity return.

This point was backed by Foltynie. “Essentially we are in exactly the same position we were in 50 years ago when it comes to treating Parkinson’s,” he said.

“We are temporarily restoring the flow of dopamine in the brain, but we are not halting the continued degeneration of brain cells. It has been a remarkably frustrating battle. Drugs that have looked really promising in laboratory tests have proved toxic or ineffective when actually put in patients.”

However, there have been some positive developments. Foltynie’s team is developing a promising Parkinson’s treatment based on a diabetes drug, while another group, at Sheffield University, and funded by Parkinson’s UK, has been using skin cells taken from Parkinson’s patients to study how other medicines might affect them in laboratory tests.

The aim is to isolate drugs that have passed safety regulations for treating other conditions but which could also have an impact in halting the degeneration of brain cells in Parkinson’s disease.

“The crucial point is that existing drugs have already passed drug safety regulations and so could be put into patients very quickly,” said Dr Heather Mortiboys, one of the Sheffield team’s leaders. “That makes this approach very attractive.”

However, only drugs that can pass through the blood-brain barrier will work in the case of Parkinson’s disease.

The barrier protects the brain against attacks by bacteria but also blocks out medicines with large molecular structures.

“We are screening thousands of drugs while rating their ability to cross the blood-brain barrier and their ability to halt brain cell degeneration – and have identified several that could have potential as drugs for Parkinson’s disease. Our project has two years to go and, yes, we are hopeful,” she said.

Source: theguardian.com

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