Hope for Duchenne myodystrophy patients
The most common form of myodystrophy – Duchenne myodystrophy – affects about 13,000 American boys. Girls with this disease are born extremely rarely, as it is caused by a defect in the gene encoding the protein dystrophin and localized on the X chromosome present in the female genome in two copies. The new drug eteplirsen, developed by Sarepta Therapeutics (Cambridge, Massachusetts), is designed to treat 13% of patients with muscular dystrophy caused by a certain mutation in the dystrophin gene. Without treatment, the muscles of such patients gradually weaken, chaining them to a wheelchair. Very often such patients die after 30 years.
12 patients participated in the clinical trial of eteplirsen (phase IIb). The drug was administered once a week intravenously in the form of a 60-minute dropper. 4 participants received a dose corresponding to 50 mg/kg of body weight, another 4 received a dose corresponding to 30 mg/kg of body weight, and the remaining 4 received a placebo.
Preliminary results published in July of this year showed that the drug increases the amount of dystrophin in muscle tissue. According to the results of the 36-week study period published in August, 4 patients who received a large dose of the drug could walk 69 meters more within 6 minutes than patients in the placebo group.
The latest results of the 48-week period showed that these four patients can walk 21 meters more in 6 minutes than at the beginning of the study. Patients who initially took placebo and were transferred to eteplirsen at week 25 are also gradually stabilizing. Their results improved by 10 meters compared to the results of 36 weeks ago, although in general their condition has worsened during the experiment period: so far, the result of their 6-minute walk is 68 meters worse than their results obtained at the beginning of the study. As a result, patients who took a large dose of the drug can walk 89 meters more in 6 minutes than those who started taking the drug six months later.
At the same time, the number of muscle fibers showing positive results when testing for dystrophin content in the group receiving a large dose of etherlirsen increased by 47%, and in patients receiving placebo during the first 24 weeks – by 38%.
Unfortunately, two patients from the group who received a small dosage of eteplirsen had a sharp deterioration at the very beginning of the study, most likely due to the progression of the disease before the start of the drug. This fact significantly complicates the interpretation of the results.
Another disadvantage of the study is the small number of participants. However, experts say that there are several cases when the US Food and Drug Administration approved the use of drugs for the treatment of rare diseases after conducting clinical trials of this scale. In any case, even if more extensive research is required, this can be done in a relatively short time.
The mechanism of action of eteplirsen is to block the reading of exon 51 of the gene encoding dystrophin. Currently, Sarepta Therapeutics specialists are working on two more similar drugs that block the reading of exon 45 and exon 50 of the dystrophin gene. These drugs will be able to help 9% and 5% of patients with Duchenne myodystrophy, respectively. However, before testing these drugs, the company needs to get approval for eteplirsen. In addition, there is competition in this area. The Dutch biotech company Prosensa and its partner GlaxoSmithKline expect to receive the results of a large-scale clinical trial of another drug blocking the reading of exon 51 this year. In a previous study involving 12 patients, this drug showed a slight improvement in the 6-minute walking test.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to Forbes materials:
In A First, An Experimental Drug May Help Boys With Muscular Dystrophy.
12.10.2012