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