Thursday, June 21, 2007

New strategies to treat neurological disorders

By Mike Nagle

20/06/2007 - Experts from around the world have gathered this week to discuss the best emerging therapies for a number of neurological disorders such as multiple sclerosis and stroke.

Thousands of scientists and clinicians have descended on the island of Rhodes, Greece for the European Neurological Society (ENS) congress and the latest drugs are the centre of attention.

One central topic at the scientific conference is multiple sclerosis (MS), a chronic inflammatory disease that attacks the central nervous system (CNS).

"About 400,000 people in Europe have MS and about one million worldwide," said the ENS president, Professor Giancarlo Comi.

"MS is still not curable. A number of new findings have been made in recent years, however, with regard to the origins of the disease and new therapeutic strategies. These new insights help us to mitigate the course of the disease and delay the development of permanent disabilities."

The scientists took time to focus on the mechanisms underlying the process of axonal degeneration which characterise the progressive phase of the disease. There is some evidence that some of these mechanisms are at least partially independent from inflammation.

According to Prof. Comi, modulating and suppressing the immune system only has a modest effect at best on the progressive phase of the disease.

"One important goal in the treatment of this severe disease has to be to develop therapies that repair the damage MS causes in nerve cells," Professor Comi said. "There is increasing scientific evidence that the course of MS is shaped by different disease mechanisms in its early and late phase."

Researchers from France, Germany and Switzerland believe they have proof for a hypothesis first posited in the late 19th century. According to this new evidence, certain stem cells differentiate very early on in human development into nerve cells or into glia cells - the maintenance and support cells in the CNS.

They showed that there are two different types of stem cells that differentiate into either glia or nerve cells. This finding from Dr Zalc, Hôpital Pitié Salpêtrière, Paris, and colleagues, contradicts the viewpoint that nerve cells form first and that glia cells then develop from them.

Prof. Comi said: "Key fundamental research findings like these could well enable MS therapy to advance in significant ways."

Professor Martin Schwab, from the University of Zurich, presented promising results for his antibody therapy that can restimulate nerve growth in animals, following injury or stroke. In the human brain, nerve fibre growth is restricted to distances below 2mm as it is inhibited by several substances found in myelin sheaths - the protective coverings found on nerves.

One of these substances is the membrane protein Nogo-A. Prof. Schwab and his team have developed an antibody that blocks this target. When they tested its effect in animals, they found that the drug stimulated nerve fibre growth over comparatively long distances substantially improved "functional restoration", such as running, swimming or gripping.

Professor Ioannis Milonas, chairman of the ENS Congress, said: "The new agent is currently being tested in a Phase I clinical study in a European network of centres for spinal cord injuries."

Another possible stroke therapy discussed at the event was developed by a group of Swiss scientists from University Hospital Zurich. Annett Spudich and her colleagues are examining the effectiveness of multidrug resistance-associated protein 1 (MRP1) as a stroke therapy in mice. They injected mice subjected to stroke injury with MRP1 substrates 17betaEG and GSNO immediately and saw a dose-dependent decrease (17betaEG) or increase (GSNO) in brain injury. If MRP1 expression was knocked out completely, these injury effects were also blocked. This indicated that MRP1 was needed by the two substrates in order to gain access to the brain.

"Strokes are the third most common cause of death and the most common cause of severe disability for adults in industrialised countries," said Professor Gerard Said, secretary general of the ENS.

He continued: "They have found that MRP1 might be a substance for transporting drugs across the blood cerebrospinal fluid barrier, a physiological barrier between the central nervous system and the blood stream."

If this proves to be the case, MRP1 could be used as a gateway through which drugs could travel directly to the brain regions affected by a stroke.