March 11, 2004
Team led by UW’s LaSpada publishes work on growth factor drop and motor neurons
Spinal cord levels of a certain growth factor fall in mice just before the onset of symptoms similar to X-linked spinal and bulbar muscular atrophy, a form of motor neuron disease. These research results are published in the March 4 edition of the journal Neuron.
While spinal and bulbar muscular atrophy is rare, its pathology is related to more common degenerative neuromuscular disorders such as Lou Gehrig’s disease and Huntington’s disease.
A team led by Dr. Albert R. La Spada, professor of laboratory medicine, neurology, and medicine in the Division of Medical Genetics, created transgenic mice with a mutation in the gene that directs the formation of androgen receptors. In mid-adulthood, the mice experienced a gradual weakness in their hind legs accompanied by degeneration of motor neurons.
The researchers found that abnormal androgen receptors interfered with a cell’s ability to produce vascular endothelial growth factor (VEGF). VEGF is important for the general health and survival of motor neurons, and has been shown to rescue motor neuron cells grown in the laboratory.
Activating the vascular endothelial growth factor pathway may be one of the ways that motor neuron cells protect themselves from damage. It is possible, La Spada added, that many motor neuron disorders might share disruption of VEGF production as part of the underlying mechanism of nerve cell degeneration.
La Spada cautioned that motor neuron disease researchers can’t exclude the role of other factors or genes at this time, and noted that additional work is needed to see if giving VEGF to affected mice would prevent or reverse their disease.
However, if increasing the levels of VEGF in the spinal cord could be shown to help guard the nerve cells from harm, this could have therapeutic relevance in the search for treatments for patients with motor neuron disease.
La Spada directs the UW Center for Neurogenetics and Neurotherapeutics. Other researchers on this study were Drs. Lisa Ellerby and Michelle LaFevre-Bernt of the Buck Institute for Age Research in Novato, Calif., and Bryce Sopher, Patrick Thomas, Ida Holm, Scott Wilke, Carol Ware, Lee-Way Jin, and Randell Libby, all of the UW.