Gene therapy could help rescue a promising treatment for Parkinson's disease (PD) shelved over safety fears, New Scientist magazine reports. The drug, glial-derived neurotrophic factor (GDNF), was withdrawn in September 2004 - just five months after it had been approved for use in patients. The biotech company that made the treatment, Amgen, stopped a US trial because it feared the protein might cause brain damage. However, a new technique for delivering GDNF via gene therapy could now alleviate these concerns.
Parkinson's disease, which affects around 120,000 people in the UK, is caused by a gradual loss of cells in the area of the brain that controls movement. This results in tremors, muscle stiffness and eventual paralysis, even though the muscles themselves are unaffected. The disease is associated with a lack of dopamine, a brain communication chemical. In 2000, a group of US scientists showed that GDNF could promote the growth of dopamine-producing nerve cells in monkeys affected by a PD-like illness, alleviating their symptoms.
Patients enrolled in Amgen's trial had showed some improvement, but the company halted the experimental treatment over fears that it would cause brain damage similar to that seen in monkeys. Now, another US biotech firm called Rheogene might have come up with a solution: they have designed a gene therapy treatment that allows scientists to precisely control how much GDNF is delivered to the brain. It involves the use of a 'switch' attached to the GDNF gene that is only turned on in the presence of a chemical called diacylhydrazine, which can be given as a pill. 'When it's off, it's off', said Mark Braughler of Rheogene.
The company hopes that it can begin clinical trials with PD patients in 2008, after completing tests on rodents and monkeys. They also say that the system could potentially be used for other gene therapy treatments, by replacing the GDNF gene with a different target gene. 'These mechanisms are important kinds of things to develop', said Mark Kay, of the American Society of Gene Therapy.