Effective use of a neurotrophic ACTH4-9 analogue 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 ACTH4-9 analogue devoid of corticotrophic and melanotrophic action in experimental allergic neuritis (EAN), an animal model for a human demyelinating disease, the Guillain-Barré syndrome (GBS). In order to mimic the clinical situation, peptide treatment was initiated at the first appearance of neurological symptoms in each animal. The ACTH4-9 analogue treatment substantially suppressed the neurological symptoms in animals with EAN, as assessed by clinical scoring and resulted in a significant improvement of motor performance. Furthermore, histological examination of the sural nerve provided a morphological basis for the beneficial functional effect of peptide treatment: more myelinated fibres were present in EAN animals treated with the ACTH4-9 analogue in comparison with EAN animals treated with saline. Further analysis of the sural nerve indicated a complete preservation of the diameter distribution of myelinated fibres in sural nerves of peptide-treated animals. In contrast, saline-treated EAN animals exhibited a significant loss of small and intermediate size myelinated fibres in the sural nerves. This study provides first evidence for the amelioration of the functional and anatomical deficits in an animal model of the GBS syndrome by an interventive synthetic neurotrophic peptide treatment.
Duckers
H J
HJ
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
Verhaagen
J
J
de Bruijn
E
E
Gispen
W H
WH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D005260:Female; D009043:Motor Activity; D009068:Movement; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone