Duchenne Muscular Dystrophy and exon skipping
New results of the Dutch trial (Prosensa) have been announced:
intramuscular injection of 2'Omethyl phosphorothioates, at a dose of125mg/kg, led to the expression of about 25% of quasi-dystrophin in the treated muscles of 4 patients. The subcutaneous administration (which allows for systemic administration) will be carried out in the next trial. This experiment has been performed in the dog and led to a low expression of quasi-dystrophin in the heart.
Regarding the English trial (MDex network) with morpholinos, the doses tested should be equivalent to those of the Dutch trial and patient enrollment has begun.
Duchenne Muscular Dystrophy and corticoids
The studies presented at the 12th WMS congress show overall that discontinuous treatment is less effective than daily treatment but that the side effects are more important in the case of daily treatment. Retrospective studies conducted in adult patients suggest that later treatment could also improve respiratory and heart function. It is necessary to confirm these findings in adult patients in a non-retrospective clinical trial, or by the establishment of an observatory.
FSH and salbutamol
The results of the French trial were officially announced at the 12th WMS congress. This randomized, double-blind, placebo-controlled trial included 112 patients with FSH. Salbutamol was administered daily at a dose of 16mg discontinuously (3 weeks with and 1 week without).
After 6 months of treatment, the results show that salbutamol has no positive effect on muscle strength of the patients (QMT or MMT score).
DMD and PTC124
PTC Therapeutics announced new results of the Phase II trial, particularly, data in the 12 Duchenne boys who received the highest dose. As a reminder, the treatment with PTC124 was given orally every day for 1 month. Three dose levels were tested: 16mg/kg; 40mg/kg and 80mg/kg. The PTC124 dose was divided into 3 times a day. Preliminary results show that 47% of patients (18/38) have some dystrophin. Two weeks after starting treatment, clinical effects become apparent:
dose-dependent reduction of CPK. Patients or their entourage observed an increase in physical activity, endurance and reduced fatigue.
These signs seem to decline 2 to 4 weeks after terminating the treatment. The effective concentration of PTC124 in the blood (determined in mice) is attained with average and strong doses. It is interesting to note that in the cystic fibrosis and PTC124 trial, there is a dramatic decrease in coughing episodes and activity of the CFTR enzyme measured.
