LETTER FROM OUR RESEARCH DIRECTOR

Dear Supporter,

Community support is the life force behind our research and I would like to thank you for visiting our web site to get more information about our research on Juvenile ALS and other neuromuscular diseases.

It is important to point out, that much of the research you will hear about on this web site is new and was leveraged by The Erin Godla Research Fund for Neuromuscular Diseases. Your donations have helped us generate some of the preliminary data showing the government that "we can do this, so give us the big dollars".

ALS remains one of the most pressing unsolved mysteries in medical science. Only a small fraction of cases are understood, and these involve rare ALS families with super oxide dismutase gene mutations (SOD). The SOD mutations appear to be a “gain of function”, in that the abnormal enzyme seems to have too much activity (rather than the “loss of function” that characterizes most genetic disorders). Why too much SOD activity throughout the body leads to specific problems with the motor neuron is not at all understood.

Juvenile ALS likewise is poorly understood. There are rare families where gene mutations have been found, but the majority of cases, such as Erin Godla, have no known cause for the disease.
What research approaches are being taken at Children’s National Medical Center?

The Center for Genetic Medicine houses approximately 90 scientists working in a collaborative and synergistic environment, applying their cumulative expertise to a large number of disorders. In the last four years since it’s founding, the Center for Genetic Medicine is emerging as one of the premier “post-genomics” research institutes in the USA. The research covers high technology genetics, ethics, molecular diagnostics, clinics, and an international clinical trial network called “CINRG”. The single largest focus of research is neuromuscular disease (disease of both muscle, and neurons leading to the muscle).
The approach being taken towards ALS and juvenile ALS is distinct from other research groups, at both the basic and clinical levels.

•Molecular definition of the neuromuscular junction using laser capture microscopy, expression profiling, antibody production, and proteomics methods.
• Definition of the sequence of events occurring during nerve loss (denervation) at the neuromuscular junction.
• Effect of SOD mutations on the molecular architecture of the neuromuscular junction.
• Definition of the sequence events taking place when muscle is re-innervated (nerve grows back to muscle).
• Increasing our understanding of the effect of known mutations in microtubule traffic in motor neuron disease (spastin pathways).
•Establishment of the Cooperative International Neuromuscular Research Group (CINRG) for conducting pediatric neuromuscular clinical trials.

The over-riding hypothesis to be tested by this research is that molecular changes at the connection of the nerve and muscle (neuromuscular junction) drive much of the pathophysiology of motor neuron disease.

This is considered an unusual approach to motor neuron disease, as current dogma is that the motor neuron cell body, in the spinal cord, is the site of disease. However, there is accumulating evidence at many fronts that suggests that factors provided by the muscle to the motor nerve via the neuromuscular junction are a major player in the pathophysiology of motor neuron disease.
The ALS and Juvenile ALS group within the Center for Genetic Medicine currently includes a director of research (Eric Hoffman), director of clinics and clinical trials (Diana Escolar), two post-doctoral fellows (Khaled Bouri, Annamaria Molon), two graduate students (Javad Nazarian, Shayma Fawwaz), and the CINRG clinical trial group (Erik Henricson, Lauren Morton). More detail on their recent progress can be found elsewhere in this web site.

Dr. Eric Hoffman, Ph.D.
Director, Research Center for Genetic Medicine
Children’s National Medical Center