Scientists gain much-needed insight into MND

Researchers at University College London, along with collaborators at King's College London, have identified a molecule that could be the key to understanding the cause of neurodegenerative diseases such as motor neuron disease (MND). This insight opens up the possibilities for developing new treatments to treat these progressive conditions.

For decades, scientists have been studying how nerves communicate with their target muscles and it is known that in diseases like MND, the sites of contact between nerves and muscles become weak. However, many mysteries remain as to how these contacts form under normal circumstances and therefore it has been very difficult to determine what has gone wrong in MND. The new work, published in the 19th November online edition of PNAS (10.1073/pnas.0806300105), is thought to put another important piece of the puzzle in place, plus offer a new possibility for developing drugs to treat MND and other neurodegenerative diseases.

It has been found that the signalling molecule, Wnt3, plays a crucial role in creating the connections between nerves and the muscles they control. It does this by assisting another molecule known as Agrin, which co-ordinates construction of the synapse and organises the elements that make up the connection. Without properly-formed synapses, the muscle cannot receive the nerve signal that tells it to contract and hence the muscle weakness that is classic in MND is seen. If researchers can construct a thorough picture to show how synapses are normally formed between nerves and muscles, they can start to look for any elements that are not working properly in people with MND. Further, this might also lead to strategies for nerve repair after an injury.

The team of researchers looked at the function of Wnt signals in chickens, mice and in cells, and in all three cases it was shown to enhance the effectiveness of Agrin. Chickens that do not have the Wnt signal in their developing wings have all of the muscle tissue that would be expected, but they do not make strong connections between nerves and muscles, thus it is known that Wnt is definitely affecting synapse formation rather than anything else related to muscles. Now that researchers understand the role that Wnt plays, they can begin to explore any role it plays in MND and whether it could be a good target for treating this type of neurodegenerative disease.

This news comes as scientists from the University of Rochester and Harvard University have identifed a gene in mice that plays a central role in the proper development of one of the nerve cells that goes "bad" in amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) and some other diseases that affect motor neurons. Furthermore, Genentech and Ipsen/Tercica have signed a letter of intent whereby they have consented to amend the court-ordered settlement agreement to permit Insmed to supply iPlex in connection with named-patient ALS programmes worldwide on a royalty-free basis. Ipsen/Tercica and Insmed also plan to enter into negotiations concerning the development of iPlex for the treatment of ALS, subject to analysing the data from ALS patients in Italy who have received iPlex and satisfying any applicable regulatory requirements.

ALS/MND is a neurological disease that affects over 350,000 of the world's population and kills over 100,000 every year (source: International Alliance of ALS/MND Associations). With limited treatment options and a life expectancy of between two and five years from the onset of symptoms, there remains an unmet clinical need. However, research continues apace and these new developments will be viewed as a step in the right direction.

Lucy Vann - Editor, CNS Drug News



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