Duchenne Muscular Dystrophy

Phrixus Pharmaceuticals has reported positive results from the preclinical studies which evaluated the effect of Carmeseal in mdx mice in a number of dosing regimens ranging from daily to weekly dosing, and at doses ranging from 3mg/kg to 300mg/kg per day, all administered subcutaneously.

The studies demonstrated that Carmeseal has a maximal effect on tidal volume, a vital measure of respiratory performance, at doses as low as 3mg/kg dosed once-a-day.

The dosing would translate into a daily dose for each patient of 105mg based on a 35kg paediatric patient compared to bolus intravenous dosing of up to 120g per patient in previous trials for sickle cell disease, a difference of three orders of magnitude.

Phrixus president and CEO Thomas A Collet said, "These results demonstrate the utility of Carmeseal in respiratory disease, the main cause of death in boys with DMD, and open a new, convenient route of administration for Carmeseal, similar to the subcutaneous administration of insulin, a route that has been found acceptable for millions of individuals in diabetes."

The mice were aged to seven months and then dosed for five months in order to allow full development of the phenotype.

"Whole body plethsymography (WBP) was used to evaluate the effect of Carmeseal."

Whole body plethsymography (WBP), an established method to understand the impact of drugs on respiratory function, was used to evaluate the effect of Carmeseal.

Phrixus chief scientific officer and research vice president Dr Bruce Markham said, "The results confirm our previous findings in animal models of heart failure, in which we demonstrated significant efficacy at doses up to two orders of magnitude lower than previously published."

Carmeseal, generically known as poloxamer 188 (P-188), has been shown to improve the efficiency of damaged hearts to pump blood and to improve the performance of damaged diaphragms.

Image: Histopathology of gastrocnemius muscle from a patient who died of pseudohypertrophic muscular dystrophy, Duchenne type. Photo: Dr. Edwin P. Ewing, Jr.