Functional and neurophysiological evidence of the efficacy of trophic pharmacotherapy using an adrenocorticotrophic hormone4-9 analog in experimental allergic encephalomyelitis, an animal model of multiple sclerosis

Chronic experimental allergic encephalomyelitis (CEAE) is a well-established animal model for the human syndrome, multiple sclerosis. CEAE has striking histological, electrophysiological and clinical analogies with multiple sclerosis and is a valuable animal model for the preclinical pharmacotherapeutical development of new putative therapeutic agents. In this paper, we describe a neurotrophic repair approach in Lewis rats suffering from CEAE. The neurotrophic peptide used is a degradation resistant adrenocorticotrophic hormone4-9 analog. The development of CEAE was examined using a combination of clinical, functional and electrophysiological parameters including somatosensory and motor evoked potentials. The latencies and amplitudes of the various evoked potentials can provide quantitative, objective data regarding the involvement of different nerve tracts in CEAE and the effectiveness of the neurotrophic peptide. Repeated subcutaneous injections of the neurotrophic peptide suppressed the development of CEAE-related clinical symptoms, markedly improved motor performance and reduced the reaction time upon thermal stimulation as compared to saline-treated CEAE animals during a 17 week follow-up study. Prolonged onset latencies of corticomotor evoked potentials and peak latencies of somatosensory evoked potentials due to the demyelination were normalized upon peptide treatment. In addition, peptide treatment substantially prevented total blocking of the corticomotor pathway in CEAE-animals and reduced the attenuation of sensory evoked potentials-related peak amplitudes as compared to saline-treated animals. The functional and electrophysiological improvements observed in CEAE-animals treated with the adrenocorticotrophic hormone4-9 analog, suggest that a neurotrophic repair approach could be of great value to promote the restoration of function in a disabling demyelinating disorder.