experimental approach to treating Parkinson's disease may need to be reconsidered
following evidence suggesting that it may make patients worse.
is a protein that is a focus for research as it is a major component of
Lewy bodies - clumps of protein that develop in nerve cells in the
brain and that are found in all Parkinson's disease cases.
Mutations in the alpha-synuclein gene have been identified as a cause of familial Parkinson's disease for a very small minority
of patients and the protein was thought by many to play role in the development of the
disorder more generally.
pharmaceutical companies, including Alnylam Pharmaceuticals, who helped fund
this research, have been developing drugs designed to reduce levels of alpha-synuclein.
A vaccine targeting
alpha-synuclein is currently in early clinical trials.
In the study, researchers
in the USA followed 1,098 Parkinson's disease patients for up to 15 years. Patients'
DNA was sequenced to determine the presence of gene variants that control how
much alpha-synuclein nerves produce. They then looked at the association
of these gene variants with patient outcomes.
expected, high levels of alpha-synuclein increased the risk of developing Parkinson's
disease. But patients who had the disease and had lower levels of
alpha-synuclein were more likely to suffer more severe motor symptoms, such as
tremor and impaired movement, and decline in cognitive skills.
Patients who produced the least alpha-synuclein had a 23
percent greater risk
of becoming wheelchair-dependent or developing
dementia than other patients.
'Our research suggests therapies that seek to
suppress alpha-synuclein in Parkinson's disease may actually accelerate the
disease process and increase the risk for developing severe physical disability
and dementia', said lead author Dr Demetrius Maraganore, chairman
of neurology at NorthShore University Health System.
far the research has only been presented at a conference, the American Academy of Neurology Annual Meeting, and
not in a peer-reviewed journal. However, Dr Maraganore says, 'it is our responsibility to release these data
because [experimental alpha-synuclein-countering treatments] may have long-term
research by the same laboratory group showed that people who inherit a DNA mutation increasing alpha-synuclein production have a 50 percent greater
chance of developing Parkinson's disease than those that do not.
Dr Maraganore suggests that alpha-synuclein is a
protein that is critical for healthy nerve function, so that too little or too
much at different points in time can be harmful.