EFFECTIVE USE OF A NEUROTROPHIC ACTH(4-9) ANALOG IN THE TREATMENT OF A PERIPHERAL DEMYELINATING SYNDROME (EXPERIMENTAL ALLERGIC NEURITIS) -AN INTERVENTION STUDY

Demyelinating syndromes are an important group of nerve disorders for which no effective therapy exists and which are life threatening in a substantial proportion of the patients. In the present experiments we assessed the ameliorative effect of Org 2766, a degradation resistant ACTH(4-9) analogue devoid of corticotrophic and melanotrophic action i n experimental allergic neuritis (EAN), an animal model for a human de myelinating disease, the Guillain-Barre syndrome (GBS). In order to mi mic the clinical situation, peptide treatment was initiated at the fir st appearance of neurological symptoms in each animal. The ACTH(4-9) a nalogue treatment substantially suppressed the neurological symptoms i n animals with EAN, as assessed by clinical scoring and resulted in a significant improvement of motor performance. Furthermore, histologica l examination of the sural nerve provided a morphological basis for th e beneficial functional effect of peptide treatment: more myelinated f ibres were present in EAN animals treated with the ACTH(4-9) analogue in comparison with EAN animals treated with saline. Further analysis o f the sural nerve indicated a complete preservation of the diameter di stribution of myelinated fibres in sural nerves of peptide-treated ani mals. In contrast, saline-treated EAN animals exhibited a significant loss of small and intermediate size myelinated fibres in the sural ner ves. This study provides first evidence for the amelioration of the fu nctional and anatomical deficits in an animal model of the GBS syndrom e by an interventive synthetic neurotrophic peptide treatment.