GDNF SLOWS LOSS OF MOTONEURONS BUT NOT AXONAL DEGENERATION OR PREMATURE DEATH OF PMN PMN MICE/

Glial cell line-derived neurotrophic factor (GDNF), a member of the TG F-beta superfamily, has been shown to be a highly potent neurotrophic factor that enhances survival of various neuronal cell types including motoneurons. To assess its therapeutic potential in treating neurodeg enerative diseases such as amyotrophic lateral sclerosis, we treated m utant mice displaying motoneuron degeneration (progressive motor neuro pathy; pmn) with encapsulated GDNF-secreting cells. Effects of GDNF tr eatment on pmn/pmn mice were compared with previous results obtained w ith ciliary neurotrophic factor (CNTF) [Sagot Y, Tan SA, Baetge E, Sch malbruch H, Kato AC, Aebischer P (1995) Eur J Neurosci 7:1313-1322]. I n contrast to CNTF, GDNF did not increase the lifespan of pmn/pmn mice . However, GDNF significantly reduced the loss of facial motoneurons b y 50%, a value similar to what was observed when CNTF was administered to the pmn/pmn mice. Surprisingly, myelinated axon counts revealed th at GDNF had no effect on nerve degeneration. Therefore, despite its po tential in rescuing motoneuron cell bodies, the inability of GDNF to p revent nerve degeneration in pmn/pmn mice suggests that its usefulness in the treatment of motor neuron diseases may be restricted to cotrea tment with other factors that act on the nerve process.