The failure of Amgen-Regeneron Partners' brain-derived neurotrophic factor in amyotrophic lateral sclerosis (ALS), delivered subcutaneously, was a reminder of the difficulties researchers have faced in developing neurotrophic factors. While the risks of developing BDNF and other neurotrophic factors remain substantial, scientists continue to believe the chance is worth taking.

Both the enthusiasm about neurotrophic factors and the problems in figuring out how to use them derive in part from the way they were discovered. "Most of this is based initially on the biology of these molecules - nerve growth factor was first - and their role in the development of the nervous system," said Ronald Lindsay, vice president of neurobiology at Regeneron Pharmaceuticals Inc. (REGN, Tarrytown, N.Y.). "In terms of their absolute physiological role, we know they have profound effects."