Cure hope for Parkinson’s sufferers

Optimism after discovery of genetic link to condition that affects Ashkenazim

THE TREATMENT and understanding of Parkinson’s disease have evolved over the past 50 years. But the most important discovery — a drug that slows or stops the progress of the condition, with its symptoms of tremor, stiffness and slowness of movement — has remained elusive.

Now a consensus is emerging among researchers that a rare genetic condition called Gaucher disease — which is more common within the Ashkenazi community than in the wider community — may hold the key.

It was in 1817 that James Parkinson identified the “shaking palsy” that would later be renamed after its discoverer. A century later, scientist Frederick Lewy observed through his microscope that Parkinson’s patients’ brains showed clear differences from non-sufferers.

In the 1970s the emergence of drugs that improved the movement-related symptoms revolutionised the quality of life for patients.

It is, however, within the last two dec- ades, with the detection of a number of genes that cause Parkinson’s, that we are beginning to appreciate they may lead the way to a cure.

In particular, recent discoveries linking the gene that causes Gaucher disease to Parkinson’s has opened up new and exciting avenues to developing powerful new treatments for both conditions.

Gaucher was first described in 1882. It is caused by the inheritance of a faulty gene (glucocerebrosidase, or GBA) from each parent, resulting in the body’s inability to break down cell products, which then accumulate in parts of the cell called lysosomes.

The disease can manifest itself in many different ways. Some individuals with two faulty GBA genes do not develop symptoms. Most are affected, although the severity may vary greatly, even within the same family.

The diagnosis is initially by the presentation of symptoms like a low blood count or enlarged spleen, followed by blood tests and genetic testing. Current treatments have emerged within the past 20 years and resulted in many affected patients living normal lives.

In the 1990s doctors noticed that some of their Gaucher patients and family members were developing the early signs of Parkinson’s. While two copies of the faulty GBA gene are

Researchers are testing new drugs for both Parkinson’s and Gaucher required to develop Gaucher disease, having one (known as carriers) or two copies increases the risk of Parkinson’s. It appears that within the UK, up to five to 10 per cent of Parkinson’s patients carry one copy of the abnormal GBA gene, rising to 25 per cent in parts of Israel.

There are two goals that follow from the discovery of the Gaucher-Parkin- son’s link. The first is to understand how the faulty GBA gene can cause Parkinson’s. The second is to develop a drug to stop Parkinson’s developing in those who have the faulty GBA gene.

Doctors and scientists at the Royal Free Hospital in London are leading research groups from Italy, Canada, Germany, USA and Israel, using sever- al approaches, including novel stem cell technology, to study the link. New drugs are already being tested.

Gaucher patients and their families can play a crucial role. The Royal Free researchers are using blood and tiny skin samples to develop stem cells in order to study the Gaucher-Parkinson’s link at a molecular level.

Importantly, this allows them to test the success of new drugs in the laboratory before offering them to patients in a clinical trial.

However, more patients and their families are needed for this vital research, currently funded by the Medical Research Council and the EU.

There is significant optimism that, with more help from Gaucher patients and from those with Parkinson’s, significant advances towards new drug therapies for sufferers of both diseases can be made in a short period. This is an edited version of a Jewish Care Health Insight lecture given this week. Professor Tony Schapira is the head of the clinical neuroscience department at the University College London Institute of Neurology. Dr Stephen Mullin is Leonard Wolfson clinical research fellow at the institute. If you would like to participate in the research at the Royal Free, email rapsodi@ucl.ac.uk for details