NIH Conference Helps Chart Course of CMT and Peripheral Neuropathy Research

[Guest guest]

NIH Conference Helps Chart Course of CMT and Peripheral Neuropathy

Research

Bethesda, MD, October 22-24, 2006.

More than 50 renowned scientists, representatives from patient

advocacy groups, and directors from the National Institutes of

Neurological Disorders and Stroke attended the NIH Conference on

Peripheral Neuropathy.

This workshop brought together many of the top scientists in the

field and encouraged them to identify the most promising avenues of

research for the next five years. The collaborations and strategies

forged at this workshop should have a tremendous impact on the

course of CMT and neuropathy research.

Among those top scientists were Dr. Shy, Dr. Scherer,

and Dr. Chance from the University of Washington School of

Medicine.

The workshop was an outgrowth of the effort initiated to have

Congress and the NIH recognize the peripheral neuropathies as

important targets for research. They were represented at the

workshop, as were the Muscular Dystrophy Association, the Juvenile

Diabetes Association, and the Neuropathy Research Foundation.

Sunday evening's session included a discussion by Dr. Dyck,

from the Mayo Clinic in Rochester, MN, of what has been done in

developing therapies for peripheral neuropathy and what still needs

to be done. He observed that while peripheral neuropathy is

extremely common, more so than stroke, there is no effective

treatment for any of the inherited neuropathies that can be caused

by any one of more than 100 gene abnormalities.

Dr. Dyck conceded that while symptoms such as neuropathic pain can

sometimes be controlled, severe pain usually responds only to

narcotics and patients can't function on narcotics. The challenge,

he concluded, is to find effective means of both prevention and

treatment, and a necessary first step will be an epidemiological

study to determine the frequency and severity of peripheral

neuropathy.

Another interesting presentation entitled, " From Cone Snail Venoms

to Therapeutics for Pain, " was made by Dr. Baldomero Olivera,

Distinguished Professor of Biology at the University of Utah. He and

other researchers have discovered that there are over 700 species of

cone snails, all of which are venomous, and that the peptides found

in their venom have implications for pain relief in humans. One—

the " shaker peptide " —is now produced as Prialt, a drug used for

intractable pain. He left the group with the admonition that

researchers need to look more often to the animal world to find

drugs to control neuropathic pain.

On Monday, October 23, 2006, the day began with welcomes and

introductions from Porter, Ph.D., Program Director of NINDS

(National Institute of Neurological Disorders and Stroke), Story

Landis, Ph.D, Director of NINDS and Scherer, M.D, Ph.D,

Chairman of the peripheral neuropathy workshop.

Presentations were then given on the following topics:

Disease Mechanisms: Axonal Neuropathies

Disease Mechanisms: Demyelinating Neuropathies

Disease Mechanisms: Neuropathic Pain

Diagnosis and Biomarkers

Therapeutic Development

Clincial Trials

Between three and five speakers addressed each topic, and the floor

was open to questions and comments.

One participant offered up the somewhat disappointing truth that

most therapies to date have failed and have cost a lot of time and

money in the process. In some cases this was due to a poor choice of

targets, candidates or models and strategies. This led another to

observe that the therapy chosen must be linked to the actual disease

mechanism, and that success is most likely when patients are

identified at a sufficiently early stage in the disease process.

The topic of pain in peripheral neuropathies also produced a lengthy

discussion centered around the paradox of how patients can lose

function and sensation and yet experience pain. Almost all patients

with one of the peripheral neuropathies experience burning

sensations, feel unpleasantly cold, have lancinating (stabbing)

pain, or suffer allodynia (pain from stimuli not normally considered

painful). Antidepressants, anticonvulsants and opioids are often

used to treat these types of pain, but it was observed that the

treatment effect is often not sufficient to control the pain and

there are also side effects and cost problems to be considered.

Dr. Kurt Fischbeck, an NIH scientist, discussed what is being done

to find possible cures for the hereditary demyelinating

neuropathies. He mentioned that both onapristone and ascorbic acid

are being tried to " down regulate " the overexpression of PMP 22 in

CMT 1A and that neurotrophic factor treatment using NT3 to promote

nerve regeneration and produce sensory improvement in 1A mouse

models has been tried at Ohio State. Finally, he mentioned the use

of Curcumin, a derivative of curry, to correct protein misfolding as

seen in myelin protein zero or CMT 1B.

The workshop concluded Tuesday morning with a " breakout " session

where the meeting attendees were divided into groups. The mission of

each group was to address one of the six topics presented on Monday

and make a list of broad research objectives that warrant emphasis

in a five-year window of activity. Each group then had a

representative present their list of objectives, highlighting those

considered to be " hot " topics. The whole group then agreed,

disagreed or simply asked questions about the list. Ultimately, the

workshop organizers will collect the edited lists, transcribe them

and provide them to the attendees.