Motor neuron growth factors

The last 5 years have witnessed a great outgrowth in the number of clinical trials testing neuronal growth factors as potential treatments in ALS. These attempts to prevent motor neuron degeneration in ALS with the use of growth factors have their basis in the profound abilities of these molecules to affect motor neuron survival in experimental animals during early development and into maturity. Recent advances in molecular biology have led to the identification of a large number of new potential motor neuron growth factors Table 1, as well as insights into the molecular mechanisms regulating motor neuron death after growth factor deprivation. A major challenge in the field is now to select those growth factors that are the most promising for future ALS trials either alone or in combination therapy.

Growth factors regulate motor neuron survival in vivo.

Two members of the prototypical family of nerve growth factors, the neurotrophins, are powerful modulators of motor neuron survival during development and into adulthood. The neurotrophin family in mammals comprises four members, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), molecules that share a significant degree of sequence homology. ^[1] An early indicator that one or more members of this neurotrophin growth factor family might affect motor neurons derived from experiments performed by Yan and colleagues. ^[2] These investigators demonstrated that motor neurons have the ability to retrogradely transport members of the neurotrophin family, including BDNF and NT-3, after these molecules have been injected into peripheral muscle. This experiment provided evidence that motor neurons express receptors for neurotrophins and might, in fact, respond to them. Localization studies have also demonstrated that skeletal muscle normally synthesizes neurotrophins (BDNF, NT-3, and NT-4) during the period of motor neuron innervation, during the maturation of synapse formation, and into adulthood. ^{[3,4] …}