Monday, September 28, 2015

RPI-78M: From Cobra Venom to Orphan Drug

RPI-78M is a modified anticholinergic alpha-neurotoxin peptide that was originally derived from an extract of cobra venom and is an antagonist of the nicotinic acetylcholine receptor. It is expected that RPI-78M may be beneficial in neuromuscular disorders where the activity of nicotinic acetylcholine receptor has been compromised. RPI-78M is being developed for the treatment of multiple sclerosis (MS). Other neurological disorders that may be served by RPI-78M include myasthenia gravis (MG), muscular dystrophy (MD) and amyotrophic lateral sclerosis (ALS).

Cobratoxin, a neurotoxin obtained from the venom of the Thailand cobra, has demonstrated several pharmacological activities that strongly support its use in this application. By employing a chemical detoxification step, the neurotoxin was rendered safe for administration to humans with minimal side effects. In a early reporet study, this modified neurotoxin demonstrated neuromodulatory, antiviral, and analgesic activity, elements associated with the multiple sclerosis condition. Modified cobratoxin demonstrated potent immunosuppressive activity in acute and chronic animal models of the disease. Following the positive signs, the drug was shortlisted for use in adrenomyeloneuropathy and clinical trials in Multiple sclerosis were planned [1].

Salient Features about RPI-78M

a: It lacks measurable toxicity. The binding with receptor is excellent suggesting that patients cannot overdose.

b: It has displayed no serious adverse side effects following years of investigations in humans and animals.

c: It extremely stable and resistant to heat, which gives the drugs a long shelf life. The drugs' stability has been determined to be over 4 years at room temperature. This is extremely unusual for a biologic drug.

d: RPI-78M can be administered orally-a first for a biologic MS drug. This will present MS patients with additional quality of life benefits by eliminating the requirement for routine injections.

On Sept 08, 2015 Nutra Pharma Corporation announced today that they have received Orphan Drug designation from the US-FDA for the Company's RPI-78M drug candidate for the treatment of Multiple Sclerosis in children.

RPI-78M induces interleukin 27 (IL27) and gamma-interferon, and it is in Phase III testing for Adrenoleukodystrophy and for additional diseases such as multiple sclerosis and herpes virus infection in earlier phases. IL27 has also been associated with inflammatory bowel disease, including Crohn's disease. Moreover, it has been shown that treatment with IL-27 reduces experimental colitis through the suppression of several inflammatory cytokines including IL- 17. In this situation, human genetic and animal studies converge to support inflammatory bowel disease and Crohn's disease specifically as new indications for RPI-78M [2].

1. Reid, P. F. Alpha-cobratoxin as a possible therapy for multiple sclerosis: a review of the literature leading to its development for this application. Crit Rev Immunol 2007, 27(4), 291-302.
2. Reid, P. F.; et. al. Modified anticholinergic neurotoxins as modulators of the autoimmune reaction. US8034777B2