ACTIONS OF CNTF AND NEUROTROPHINS ON DEGENERATING MOTONEURONS - PRECLINICAL STUDIES AND CLINICAL IMPLICATIONS

Spinal motoneurons innervating skeletal muscle were amongst the first neurons shown to require the presence of their target cells to develop appropriately. Isolated embryonic chick and rat motoneurons have been used to identify neurotrophic factors and cytokines capable of suppor ting the survival of developing motoneurons. Such factors include cili ary neurotrophic factor (CNTF), which is present physiologically in hi gh amounts in myelinating Schwann cells of peripheral nerves, and brai n-derived neurotrophic factor (BDNF) which is synthesized in skeletal muscle and, after peripheral nerve lesion, in Schwann cells. These fac tors have been further analyzed for their physiological significance i n maintaining motoneuron function in vivo, and for their potential the rapeutic usefulness in degenerative motoneuron disease. Both CNTF and BDNF are capable of rescuing injured facial motoneurons in newborn rat s. Furthermore, CNTF prolongs survival and improves motor function of pmn mice, an animal model for degenerative motoneuron disease, by prev enting degeneration of motoneuron axons and somata. Thus treatment of human motoneuron disease with neurotrophic factors should be possible, provided that rational means far application of these factors can be established considering also the appearance of potential side effects.