org-2766 and Diabetic-Neuropathies

Topics: Adrenocorticotropic Hormone; Animals; Anticonvulsants; Cells, Cultured; Diabetic Neuropathies; Disease Models, Animal; Humans; Melanocyte-Stimulating Hormones; Nerve Regeneration; Nervous System Diseases; Neurons; Peptide Fragments; Pro-Opiomelanocortin; RNA, Messenger

The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDTwarmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDTcold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Diabetic Neuropathies; Double-Blind Method; Humans; Middle Aged; Nerve Growth Factors; Peptide Fragments

In this study we report a randomized double-blind, placebo-controlled trial to evaluate the effect of ORG 2766 in IDDM patients with peripheral neuropathy. Sixty-two patients were selected based on the following criteria: abnormal vibration perception threshold above the 95th-percentile adjusted for age and/or abnormal warm temperature threshold, both measured in the right hand. The patients were randomized into two treatment groups after baseline studies: Group 1 was treated with placebo and Group 2 was treated with 3 mg of the ACTH4-9 analogue ORG 2766 every 24 h. The total study period was 1 year. After 1 year of treatment there was a significant improvement in vibration threshold in Group 1 compared to Group 2. No other parameters improved in the study period. The number of patients selected may have been too small to detect a more important treatment effect. We conclude from this study that ORG 2766 can improve vibration threshold, indicating large myelinated fibre function, but does not affect any of the other neurophysiological function tests.

Topics: Adrenocorticotropic Hormone; Adult; Anticonvulsants; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Peptide Fragments; Perceptual Disorders; Psychomotor Performance; Sensory Thresholds

The effect of treatment of an existing neuropathy in streptozocin-induced diabetic rats with the ACTH4-9 analogue ORG 2766 was examined. Four groups of rats were studied: group 1 consisted of age-matched, non-diabetic controls and groups 2, 3 and 4 of diabetic rats. Sensory and motor nerve conduction velocity (SNCV and MNCV) were measured at weeks 0, 4, 6, 8 and 10. Four weeks after the administration of streptozocin (STZ) all diabetic rats showed a significant slowing of SNCV and MNCV. Treatment was then started: group 2 was treated with placebo, group 3 with a low dos (1 microgram) of ACTH4-9 subcutaneously every 48 h, and group 4 with a high dos (10 micrograms) of ACTH4-9 subcutaneously every 48 h. The animals treated with the high peptide dosage showed a significant improvement in both SNCV and MNCV from week 6 onwards, whereas this beneficial effect was not demonstrated for the rats treated with the low dosage. This study demonstrates that the ACTH4-9 analogue ORG 2766 can ameliorate existing diabetic neuropathy in STZ-induced diabetic rats.

Topics: Adrenocorticotropic Hormone; Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response Relationship, Drug; Male; Motor Neurons; Neural Conduction; Neurons, Afferent; Peptide Fragments; Rats; Rats, Wistar; Reference Values; Sciatic Nerve; Tibial Nerve; Time Factors

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Cisplatin; Diabetic Neuropathies; Humans; Peptide Fragments

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Hydroxydopamines; Male; Oxidopamine; Peptide Fragments; Phenylephrine; Rats; Rats, Inbred Strains; Tyramine

An injection of streptozocin (STZ) was used to study diabetes-induced peripheral neuropathy in rats. In such rats the values of motor nerve conduction velocity and sensory nerve conduction velocity were decreased compared with the values obtained in nondiabetic controls from 3 wk after STZ injection onward. In recent years it has been extensively documented that peptides related to ACTH and MSH exert a neurotrophic effect on the nervous system that results in enhanced recovery of function after mechanical nerve damage. This article documents the beneficial effect of the peptide Org 2766, an ACTH-(4-9) analogue, in diabetic peripheral neuropathy. Chronic subcutaneous treatment of diabetic rats with Org 2766 results in a significant enhancement of both motor and sensory nerve conduction velocity compared with saline-treated diabetic rats. Histological analysis of cross sections of the sural nerve showed no difference in the total number of nerve fibers in saline- or peptide-treated diabetic rats. In contrast, a difference in fiber size distribution was demonstrated; i.e., the sural nerves of diabetic rats contained fewer thick myelinated fibers. Treatment with Org 2766 resulted in a normal distribution. Apparently, the peptide Org 2766 has a protective action on nerve fibers and nerve function during STZ-induced diabetes.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Female; Motor Neurons; Nerve Fibers, Myelinated; Neural Conduction; Neurons, Afferent; Peptide Fragments; Rats; Rats, Inbred Strains; Reference Values; Spinal Nerves; Sural Nerve