Neurotrophins and other growth factors in diabetic neuropathy.

There is enthusiasm for the application of knowledge concerning neurotrophins and other growth factors to human neurologic disease. New neurotrophins and other growth factors or inflammatory mediators that influence neurons and axons have been recently identified. Diabetic neuropathy may be an ideal testing ground for these substances because specific neurotrophins and growth factors could theoretically prevent loss of diabetic dorsal root ganglion (DRG) cells or enhance regeneration of diabetic nerves. Several of the neurotrophins support DRG cells in culture or prevent their loss during neonatal development, and a few help prevent retrograde loss of adult DRG cells after axotomy. Early Phase I trials suggest that nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 are reasonably safe agents as administered in short-term trials to humans, but there are lingering experimental doubts. For example, it has not been established whether DRG cells are targeted by diabetes. Additional work suggests that simultaneous and sequential cocktails of trophins are required to support and rescue neurons and that the use of single agents may not be sufficient. Finally, it in uncertain whether trophins might act as a general tonic for DRG cells to prevent diabetes-related injury or whether they are actually deficient in human diabetic patients.