The first studies of human gene therapy for Parkinson's disease have shown that the technique is safe and can reduce symptoms for patients, two groups of researchers have reported.
All of the 24 patients who received therapy in the two separate trials received some benefit and none had any significant side effects, researchers reported at neuroscience meetings Tuesday and last week.
Gene therapy has a tarnished reputation because of problems encountered in trials involving other diseases, said Katie Hood, deputy chief executive officer of the Michael J. Fox Foundation for Parkinson's Research.
The Food and Drug Administration temporarily halted gene therapy trials in 1999 after an 18-year-old being treated for a mild genetic disorder died after a violent reaction to the procedure. Trials were halted in 2005 after three French children being treated for inherited immunodeficiency disease developed leukemia and one of them died.
"It's very encouraging that two companies were able to show benefits with no significant adverse effects," Hood said. "Safety is obviously the first hurdle."
Experts and the researchers themselves, however, cautioned patients against investing too much hope in the findings because Parkinson's studies are notorious for showing placebo effects.
Only when the techniques are tested in controlled trials, now in the planning stages, will researchers be able to determine whether the benefits are real and lasting.
Parkinson's, which strikes as many as 100,000 Americans each year, is characterized by severe tremors and rigidity in the limbs, and loss of muscle control. It results from the death of brain cells that produce the neurotransmitter dopamine, which plays a key role in transmitting commands from the brain's muscle-control centers. The disorder's cause is unknown.
Both teams used the same gene therapy technology, inserting a desired gene into the common adeno-associated virus. AAV readily infects humans but has never been shown to cause disease.
One team, led by Dr. Matthew J. During of the Weill Cornell Medical Center in New York, used a gene that is the blueprint for an enzyme called glutamic acid decarboxylase. That enzyme converts chemicals in the cell into a neurotransmitter called GABA, which is essential for controlling muscle movements.
Earlier studies have shown that Parkinson's disease is marked by a deficiency of GABA in a part of the brain called the subthalamic nucleus. Injecting GABA into the brain can ease disease symptoms, but the neurotransmitter is quickly cleared, limiting its benefits.
During's team injected one side of the brains of 12 patients with one of three different concentrations of the gene therapy agent.
He told Tuesday's meeting of the Society for Neuroscience in Atlanta that all 12 patients had an improvement of at least 25% on a conventional scoring system used to assess the severity of Parkinson's symptoms, four of whom improved at least 37% and five others 40% to 65%.
The benefits have persisted for a year. Placebo benefits are usually transient, researchers noted.
Brain imaging showed an increase in metabolism on the side where patients received the gene therapy, and the amount of increase correlated with the degree of improvement in symptoms, During said.
The gene therapy agent was manufactured by Neurologix Inc. of Fort Lee, N.J., a company created by During and his colleagues to commercialize the technology. Neurologix paid for the study. During said the neurologists who assessed the patients' condition had no financial ties to the company.
The second study, led by Dr. William J. Marks Jr. of UC San Francisco, used the gene for a growth factor called neurturin, which is closely related to the better-known growth factor GDNF.
Studies have shown that injecting GDNF into the section of the brain known as the putamen can impede, and possibly reverse, the loss of dopaminesecreting cells.
Marks and his colleagues injected 12 Parkinson's patients with one of two doses of the gene therapy agent. Patients receiving the lower dose had a 40% decrease in Parkinson's symptoms, and those receiving the higher dose had a 50% reduction, he reported at last week's American Neurological Assn. meeting in Chicago. The researchers have monitored the patients for nine months.
"This is a clinically meaningful benefit that has been sustained over time," Marks said.
The gene therapy agent used by Marks was developed by Ceregene Inc. of San Diego. Marks said he had no financial ties to Ceregene.
The company paid for the trial with the Fox foundation. The foundation recently announced it would invest $1.9 million in a controlled trial of the approach.