Research and Going Forward

November 15, 2008 at 10:45 pm

Please note the disclaimer at the top of the thread.

[B]Research and going forward in GBS and CIDP. [/B]

There is an international Inflammatory Neuropathy Consortium. In this, efforts to advance research in GBS and CIDP include
Cochrane reviews of existing data
A database of people having MMN
The PERINOMS project to get better measures of clinical change in patients
The EGOS project to grade outcome in GBS
Genomics and SNiP databases
SIDGBS: second dose of immunoglobulin in GBS trial to see if this helps those that do not respond adequately to the first course of immunoglobulin
Alumtuzumab trial.

The Cochrane Collection evaluates the medical evidence for practice activities in diseases. This is part of evidence based medicine. GBS and CIDP, being rare, do not have as many randomized controlled clinical trials as most prevalent diseases often do. The number of subjects at any place are limited and the variety in disease courses and treatments are considerable.

Many more clinical trials are needed especially in mild GBS, AMAN, the Miller Fisher variant and other variants, combinations of treatments, and other ways to alter the immune response. As well, better ways to classify and describe the neurologic features and severity of GBS and CIDP are needed and well as to classify response to treatments.

There was a survey of CIDP patients in 2007 and 2008 that will be published soon looking at other medical factors, characteristics, treatments, duration, benefits of treatment, and outcomes as well as socioeconomic impact. Some of this is reported in other sections.

There was a clinical trial in humans using methotrexate to help control CIDP and permit less immunoglobulin to be used. This trial was not successful by itself, but does serve as a pilot of the issues that need to be considered for other trials in CIDP particularly how to get the most uniform starting population, how to alter other treatments, how to measure outcome in an accurate and functionally relevant manner, etc.

There was an international clinical trial of interferon beta 1a. Unfortunately not nearly as many people participated as needed and there is missing data. It was also a short trial and this may not have been optimal.

Potentially promising agents that alter the immune response
Rituximab (Rituxan, anti-CD20) that wipes out B lymphocytes that make antibody.
Eculizumab and other monoclonal antibodies that affect complement.
Natalizumab a monoclonal antibody that affects integrins and thus cell migration as occurs with T lymphocytes.
Lamotriguin that alters the axonal depolarization by sodium channel blockage
Alemtuzumab (Campath, anti-CD52) that wipes out lymphocytes.
Infliximab that affects TNF alpha, an important effector molecule in inflammation.
IFN beta 1a

One of the presenters talked about an animal model for GBS in which one can study nerve damage caused by anti-GM1 and anti-GD1a antibodies. The presence of these bad antibodies delays nerve healing and leads to incomplete recovery. He has a mouse deficient in a central component of complement as well as one defective in the Fc gamma receptor also important in the activity of complement and can use these to study the effect of complement on the damage in CIDP.

One of the presenters talked about erythropoietin as protective of the nervous system in MS and in stroke. He is testing this in the lab using nerve cells in culture and there seems to be promise. The concern is that erythropoietin can increase the risk of blood clots and GBS can as well, so this might be an issue in clinical use. He said that chemical modification of the erythropoietin can still result in the nerve regeneration/repair but does not allow the molecule to increase the blood thickness in the same way that regular EPO does. This medicine will need to be tested in a live mouse model of GBS and then may can be tested in humans to see if it helps nerves to heal. _______________________________________________________________-
Special thanks to Drs. Hughes, Koshi, Gorson, Cornblath, Sheikh, and Ashbury as well as the many other experts that commented on research issues at other times. Their amazing efforts in this rare set of disorders need to be recognized.