Science News

Drug triggers repair in MS-damaged brain

Thu, 10th Oct 2013

Chris Smith

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A drug that can reverse the damage done by the disease MS (multiple sclerosis) has been Demylinisation in MSdiscovered by US scientists.

Multiple sclerosis affects about 1 person in every thousand. It's a progressively disabling disease caused by the immune system attacking a protective layer called myelin - made by cells called oligodendrocytes - that surround and insulate nerve fibres in the brain and spinal cord.

The loss of myelin causes affected neurones to fail to transmit faithfully the messages that should be passsing along them, leading to sensory, visual and movement problems and, in severe cases, paralysis.

But, there is evidence that, if the immune assault can be curtailed, a population of dormant brain stem cells, called oligodendrocyte precursors, can replace the lost myelin-making oligodendrocytes, leading to the re-insulation of the neurones denuded by the disease symptomatic improvement.

However, these cells appear to be too few in number to adequately replace those lost to the immune attacks, so recovery is incomplete at best.

Now, by screening over 100,000 different drugs, a team in California have uncovered one that strongly stimulates the production of new myelin-producing cells, known as oligodendrocytes, leading to the repair of MS brain lesions.

Ironically, the drug identified by Scripps Institute scientist Luke Lairson and his colleagues, is benztropine, which has been used for years to treat tremor in people with Parkinson's Disease. As such, it is already licensed for human use.

Benztropine works by blocking the action of a nerve signalling chemical called acetyl choline, which also keeps the oligodendrocyte precursors cells that make myelin in a quiescent state.

Interrupting this suppressive signal with benzotropine awakens the stem cells, triggering them to multiply and turn into new oligodendrocytes.

The team made the discovery by incubating the precursor cells with drug molecules in a culture dish before looking for markers of myelin production.

Promising leads were then tested further by growing precursors cells alongside cultured neurones and looking for evidence of successful myelination. When benztropine emerged as the most powerful candidate tested, the team then administered the agent to mice with the rodent equivalent of MS.

Treated animals showed dramatic improvements in their symptoms, and, under the microscope, significant re-myelination had taken place. In some further tests, the team also administered a low dose of immune-suppressing drugs; given alongside the benztropine, this regimen resulted in an even larger clinical benefit.

The researchers nonetheless urge caution. They point out in their paper in Nature, where the work is published, that, "benztropine has significant neurological and psychiatric side effects," emphasising that further preclinical and clinical evalution will be needed before the findings can be translated to the clinic.

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This is a really interesting study. Previous approaches attempted to halt damage to nerves by the immune system - almost damage limitation. But this is an effort to restore oligodendrocyte differentiation and thereby myelin maintenance to halt damage and potentially repair it. Fascinating stuff. simonbishop, Thu, 10th Oct 2013

Great news. If this turns into a viable MS treatment, what sort of time-to-market could we expect, considering that it would be based on a well understood drug? Skyli, Thu, 10th Oct 2013

I suspect it would have to be in trials for a long time. Benzatropine has many side effects as well as its use in Parkinsons. The study says they are looking into other drugs and chemicals that remyelinate nerves, possibly by a completely different mechanism - perhaps they might find something in there that has fewer side effects and could come to market quicker? simonbishop, Thu, 10th Oct 2013

In all likelihood, this is in trials already; the publication cycle is always behind what's actually happening on the ground. I suspect that they'll run a multi-way trial looking at a combination of immunosuppressant, benztropine and benztropine/immunosuppressant interventions. The paper hints at this at the end where it shows that lower doses of both in combination achieves the same benefits as intense immunosuppression alone, but without the obvious side effects of heavy immune suppression.

I will be interested to see what the people who have been doing the Campath trials make of this. Here is the link to an interview Alistair Coles gave me in 2008 on what they were finding: http://www.thenakedscientists.com/HTML/content/interviews/interview/1012/ chris, Sun, 13th Oct 2013

Thank you Chris; a very interesting article.

Does anybody know what the status of CamPath is at the moment? Skyli, Mon, 14th Oct 2013

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