August 8, 2003
A study reported in the journal Science on a novel form of gene therapy that delayed ALS symptoms in mice has "great potential" for improving motor neuron survival, comments Dr. Lucie Bruijn, science director and vice president of research for The ALS Association.
"For some time there has been a concerted effort among researchers to identify methods to enhance or encourage motor neuron survival," said Dr. Bruijn on the study published in the August 8 issue of Science. "Delivery of nutrients to the motor neuron via gene therapy has great potential as indicated in this study. This study also reaffirms the potential of IGF-1 as an effective treatment for ALS."
A research team led by investigators Dr. Jeffrey Rothstein of Johns Hopkins University and Dr. Fred H. Gage of The Salk Institute for Biological Studies report that delivery of IGF-1 (insulin-like growth factor) can be efficiently transported from muscle to motor neurons using a virus as the transport mechanism. The investigators also report that IGF-1 showed beneficial effects in a transgenic mouse model of ALS even into late stage of the disease.
Dr. Rothstein, recognized for his ALS expertise including ALSA-funded studies of excess glutamate and the dysfunction of the glutamate transporter in ALS, has for many years worked with The ALS Association, serving on its Scientific Review Committee including chairing the Committee on several occasions.
According to the Science article, the investigators used an adeno-associated (respiratory) virus to initiate delivery of two neurotrophic factors (NTFs), IGF-1, and GDNF. Although numerous clinical studies have sought to test the safety and effectiveness of neurotrophic factors in ALS, delivery (crossing the blood-brain barrier) has always proven problematic. In this study, the therapeutic proteins are delivered into the muscle via the virus and travel from the muscle back to the spinal motor neurons.
In a current ALSA-funded project, Dr. Eva Feldman at the University of Michigan is studying various viral vector systems to deliver therapeutic proteins to the motor neurons. ALSA has also funded Dr. Feldman's prior work in this area.
Johns Hopkins reported that a clinical trial using IGF-1 gene therapy is being planned, but that is a year or so away. Meanwhile, in a collaborative effort with the Great Lakes ALS Consortium, ALSA is co-funding a multi-center clinical trial of Myotrophin™ (IGF-1). For more information go to Myotrophin.
Contact: gcash@alsa-national.org
