Nerve Conduction - RESEARCH

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Nerve Conduction - RESEARCH

http://www.msaustralia.org.au/publications/mslife/mslife_issue_11/nerv

econduction.html

When medical science finds a way to stop all MS attacks — what then?

Will it be possible to repair the damage MS has already done? This

question has propelled neurologist and molecular neuroscientist

G. Waxman, MD, PhD, professor and chairman of Neurology at

Yale University, throughout his career. As an acknowledgement of his

painstaking, groundbreaking research on nerve fibres that have lost

their protective myelin coat and become, in medical

terms, demyelinated, the American Academy of Neurology and the

National Multiple Sclerosis Society has awarded

Dr Waxman the prestigious 2002 Dystel Prize for MS Research, on

April 16th in Denver, Colorado.

Dr Waxman, who also directs Yale's PVA/EPVA Centre for Neuroscience

and Regeneration Research Centre of Yale University in West Haven,

Connecticut, says the path to his current work reaches back to his

medical student days in the 1970s. While attending the Albert Einstein

College of Medicine, he became enamoured of the work of Dr

Huxley, the Nobel Prize-winning physiologist who discovered the sodium

channel.

" When I did some of my first research in London, I got to meet Huxley "

Dr Waxman recalled. To his disappointment, his hero had left the field

of sodium channels. " At that time it was a mystery why, " he said.

Nevertheless, young Dr Waxman was inspired to devote his life to

studying nerve impulse conduction in normal, demyelinated and

regenerating nerve fibres.

To understand this work, it's necessary to learn a little about nerve

conduction. Nerve fibres (or axons) are like long chutes that act as

delivery pathways for electrical signals travelling from one site to

another within the central nervous system (the brain and spinal cord)

or from the central nervous system to sites all over the body. Running

along the axons are clusters of different kinds of pore-like molecules

designed to admit particles – or ions – of salts or minerals.

Chief among them are sodium channels. They allow electrical signals to

be created. Each sodium channel has a kind of trap door that opens and

closes to let through sodium ions in response to signals from the

axon. Dr Waxman explained, " Some sodium channels open and close

slowly, some rapidly, some have an on/off switch that's easy to turn

on, others have a switch that's hard to turn on. " A second type of

pore-like molecule is the potassium channel. Potassium channels act as

a brake. Sodium channels and potassium channels operate together,

generating sequences of precisely timed nerve impulses that carry

information within the brain and spinal cord. Dr Waxman's early

research showed that when the axon's protective myelin sheath is

damaged, as happens in MS, the exposed parts of the axon don't contain

enough sodium channels to power nerve conduction. The lost or weakened

nerve messages cause many MS symptoms such as poor vision or loss of

motor power.

Genes run the show

Dr Waxman wanted to know what happened next. " We learned there are 10

different genes in the nerve cell's DNA that produce different sodium

channels. When an axon is damaged, the sodium channel genes that

should be turned on are turned off, and those that should be turned

off, turn on. The cell produces the wrong kind of channel.

Dr Waxman By Diane O'Connell The Dystel Prize for MS

Research was established in 1994 by n and Dystel in honour

of their son, , whose promising legal career was cut short by

progressive MS. The prize is given jointly by the NMSA and the

American Academy of Neurology and is the only professional award given

annually to honour outstanding contributions to MS research.

It's like putting a type A battery into a radio that needs a type C. "

The damaged nerve cell may continue to fire in an inappropriate buzz,

like static on a radio, or pins-and-needles, or numbness, or pain.

Studying laboratory animals, Dr

Waxman and his colleagues recently found that special nerve cells in

the brain called Purkinje cells also produce the wrong kind of sodium

channels in lab animals that had lost their myelin.

When the researchers studied autopsy tissues from people with MS, they

found the reason why: " Something linked to theMS was causing a sodium

channel gene to turn on inappropriately, " Dr Waxman said. When this

`off' gene is turned on, the cell activity becomes strikingly

perturbed and it fires in inappropriate patterns. " The Purkinje cells

are supposed to fire in a precise pattern, enabling us to play piano,

do gymnastics, or throw a football, " he explained. " In a person with

MS, these essential cells may talk nonsense to each other, and that

causes loss of coordination. "

" If we can learn how to control these genes or the channels they

produce, we may be able to improve function in

people with MS. "

Regaining conductivity

Dr Waxman's research has also revealed that damaged axons can

reorganise themselves and establish new sodium channels, even in areas

that have been stripped of their myelin.

The new channels restore the ability of the axon to conduct electrical

impulses. " This prompts us to ask what triggers this process, " said Dr

Waxman. " Can we induce this change? In other words, can we develop

therapies that will cause people with MS to have remissions? " Dr

Waxman and his research team are searching for the " promoters " , or

switches, that control the production of new sodium channels. In a

third area of research, Dr Waxman is looking into ways to rescue nerve

fibres before they die. It is now well known that some nerve fibres

degenerate, or even die, in MS.

Researchers think this may be the cause of permanent disability. Dr

Waxman's research suggests that nerve fibres die when calcium ions

flow, in inappropriately large amounts, into nerve fibres. Dr Waxman's

research has identified the molecules that permit this damaging inflow

of calcium. " Our hope is to develop drugs that will block the pathway,

and protect the axons by keeping the calcium out, " he said. " If we can

do that, we have a good chance of preventing degeneration and loss of

axons in the brain and spinal cord. "

A science fiction world

Twenty years after meeting Dr Huxley in London, Dr Waxman discovered

why his hero had left the field of sodium channels. In 1995, Dr Waxman

edited a medical text called The Axon, for which Dr Huxley wrote an

introductory chapter. " In the 1960s, any idea of analysing the sodium

channels by the methods of molecular neurobiology would have seemed to

us to be science fiction, " Dr Huxley wrote. " Any idea that such work

would be relevant to humans was beyond science fiction, " he said

privately.

" Today, we're living in his `science fiction,' " Dr Waxman said. " The

molecular revolution has given us powerful research tools. Hopefully

we can make all this science relevant to humans, especially to people

with MS. " Diane O'Connell is a freelance writer who frequently writes

about medical topics.

Reprinted from Inside MS, Summer 2002, with permission of the National

MS Society, USA. The National MS Society (USA) is proud to be a source

of information about multiple sclerosis. Our comments are based on

professional advice, published experience, and expert opinion but do

not represent individual therapeutic recommendation or prescription.

For specific information and advice, consult a qualified physician.

The International Reid Nicholson Award has been established to

recognise people who are or who have been caregivers to people with

multiple sclerosis and who have demonstrated outstanding commitment

and devotion in the support of a loved one.

http://www.msaustralia.org.au/publications/mslife/mslife_issue_11/nerv

econduction.html