Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis

The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA a nd brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle bio psies from five patients with amyotrophic lateral sclerosis (ALS), six pati ents with other neuromuscular diseases and eight healthy control persons. A ll five patients with ALS had higher GDNF mRNA expressions in their biopsie s than the healthy control group (almost a three fold increase). Among the other patients only one, who had a rapidly progressing toxic polyneuropathy , showed a GDNF mRNA expression above those of the controls. The BDNF mRNA expressions in the biopsies from the ALS patients were in the same range as those from the healthy controls, although the mean value of the ALS patien ts was higher. The only biopsy that showed a markedly higher BDNF mRNA expr ession was taken from one patient with progressive muscular atrophy. These results suggest that increased GDNF mRNA expression in muscle is an unspeci fic response to ongoing denervation and that this response is maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves to be a constant finding in ALS the rationale for the use of GDNF as a therapeutic agent in ALS must be questioned. (C) 1999 Elsevier Science B.V. All rights reserved.