 |
 |
The source of this article is Michael J. Fox.com: http://tinyurl.com/djgzp Reprieve for 'Risky' Parkinson's Drug By Peter Aldhous, New Scientist Magazine January 26, 2006 THE first thing his family noticed was the return of his smile. Having earlier watched Robert Suthers's face turn into the "Parkinson's mask" as his facial muscles became less responsive, this was a hopeful sign. GDNF, or glial-derived neurotrophic factor, the experimental drug he was taking to treat his Parkinson's disease, appeared to be working. But in September 2004, after Suthers had been on the drug for just five months, it was controversially withdrawn because of safety fears. Amgen, the biotech giant running the trial that included Suthers, became concerned that high doses of GDNF might damage the part of the brain important for balance and posture, as seemed to happen in tests on monkeys. Now Rheogene, a biotech firm in Norristown, Pennsylvania, has come up with a technique that might address these concerns. It has developed a "safety switch" that should allow GDNF to be delivered to the brain by gene therapy, precisely controlling the amount produced. By hooking this switch to the gene for GDNF, it might be possible to control the amount of GDNF produced in the part of the brain damaged by Parkinson's, so that each patient gets a high enough dose to be therapeutic, but without unwanted side-effects. The company has already won the backing of The Michael J. Fox Foundation for Parkinson's Research, which plans to invest up to $4.2 million in the company's research over the next four years. "This technology looks exciting," says foundation president Deborah Brooks. "GDNF remains, in our view, one of the most promising therapies for Parkinson's disease." Rheogene's switch is based on the receptor for ecdysone, a hormone that makes insects shed their external skeletons. The ecdysone receptor binds to the genes that control this moulting, switching them on in the presence of the hormone, or a molecule called a diacylhydrazine that mimics it. This molecule can be given as a pill and has no effect on the body other than activating the receptor. The complete switch consists of the gene for the receptor, the DNA sequence to which it binds, and a "promoter" sequence that drives the activity of the target gene, in this case the one for GDNF. When introduced into a cell, the receptor is synthesised and completely shuts down the target gene until it is activated by the diacylhydrazine (see Graphic). "When it's off, it's off," says Mark Braughler, Rheogene's vice-president for therapeutics. The system may offer finer control than other technologies designed to control the action of genes. By giving more or less diacylhydrazine, doctors will be able to regulate the amount of protein produced. To treat Parkinson's, viruses engineered to contain Rheogene's switch, hooked to the gene for GDNF, will be injected deep into the brain, where they should be taken up by brain cells. After completing extensive tests in rodents and monkeys, Rheogene hopes to begin clinical trials in 2008. It is not just Parkinson's patients who could benefit. Rheogene's system could be useful in treating many diseases simply by replacing the GDNF gene with a different target gene. "These mechanisms are important kinds of things to develop," says Mark Kay of Stanford University in California, president of the American Society of Gene Therapy. Amgen says it is keeping an open mind on the prospects for GDNF, if a way of delivering the drug safely and effectively can be found. "We want to explore how this could still be used," says Donna Masterman, who heads the company's GDNF development programme. But that's scant consolation for the patients who were enrolled in Amgen's trial, who are fighting for access to the drug through the courts. "It's been devastating," says Kristen Suthers, whose father has deteriorated significantly since it was halted. From issue 2536 of New Scientist magazine, 28 January 2006, page 13 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn