Australian researchers working with mice have found a way to halt the progressive nerve damage that makes multiple sclerosis (MS) such a debilitating disease.
Steven Petratos, leader of the Monash University team, said he was confident that clinical trials less than a decade away would show the therapy also worked in humans.
Working with colleagues in the United States and Canada, the Melbourne team identified a protein, collapsin response mediator protein 2, or CRMP-2, that in MS patients is modified. They suspect CRMP-2 triggers nerve cell damage when it interacts with another specific protein in the brain, spinal cord or optic nerves.
They managed to block both the modification of CRMP-2 and the interaction. Using gene therapy to breed so-called block-out mice, they found nerve damage could be stopped.
No nerve cell damage
"What we did was to take that gene, make it resistant to damage, and reinsert it using a viral delivery mechanism into the nervous system," he said. "What we found with those mice is that when we tried to induce the disease we didn't see any nerve cell or nerve fibre damage."
The research, published in the latest issue of the journal Brain, was welcomed by Multiple Sclerosis Research Australia chief executive Jeremy Wright.
"It's one of the most exciting breakthroughs we've had," Wright said. "It verifies what science says about the disease - that it's about the immune system going a bit skew-whiff and not having the genetic controls all in place." Wright said the research helped explain how drugs now in use are working.
Women are three time more likely than men to get MS, a disease thought to be caused by the immune system malfunctioning and launching attacks on the myelin cells around nerve endings. The drugs now in use attempt to weaken the whole immune system, and so weaken its attacks. The breakthrough flagged by Petratos offers a different approach.
Progression gets you to the wheelchair
"This is the first treatment where we're starting to get specific attacks on specific molecules," Wright said. "We're blocking the attacks as opposed to trying to dampen the immune system, which means you're not wasting the treatment on the rest of the immune system."
Petratos is buoyed by similar research work he has done on Alzheimer's, another neurological degenerative disease, and one where regulatory authorities have approved the gene therapy approach. Hospital patients in the US have been recruited for clinical trials on gene therapies to treat Alzheimer's.
Having approvals in the bag means clinical trials on MS patients could be less than 10 years away.
"It's the progressive form of MS that responds very poorly to conventional methods of treatment," Petratos said.
"If you have limited damage to nerve fibres (and get the course of injections he expects will form the therapy) you won't end up getting progression. It's the progression that makes you go from ambulant to being in a wheelchair."
(Sapa, May 2012)
The amazing brain