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“This is primarily a safety trial, and we can confidently report that safety has been achieved.”

Mendell adds that an additional goal of this study is to lay the groundwork for future gene therapy trials by establishing the ideal dose for treatment. “In this trial, two doses have been tested, and another will be required before completion of the study,” he says, noting that “by all indications,” a higher dose will be safe to administer.

Results are expected when all participants have completed the study.

Development of EN101, an experimental drug for myasthenia gravis (MG) that blocks the synthesis of the enzyme acetylcholinesterase, will continue, but under the auspices of a new company. In December, the London-based biotechnology firm Amarin acquired Ester Neurosciences, the Israeli company that first developed the drug. (See Research Updates, November-December 2007).

Amarin is now overseeing an ongoing phase 2a trial of EN101, in which three different doses of the drug are being compared to Mestinon, a standard treatment for MG.

Acetylcholinesterase, the target of EN101, is an enzyme that degrades acetylcholine, a carrier of signals from nerve fibers to muscle fibers. Interfering with this enzyme’s action boosts acetylcholine levels, which is a logical way to increase strength and function in MG. Mestinon blocks the acetylcholinesterase enzyme after it’s

been synthesized, and EN101 prevents its synthesis.

In December, Amarin said that “interim data suggest EN101 may have superior efficacy, longer duration of action, [and] a more favorable side effect profile and dosing regimen, as compared with Mestinon.”

The company said its focus will be on completing the phase 2a study and laboratory studies in preparation for beginning a phase 2b or phase 2-3 trial.

For more information, see www. amarincorp.com.

Survival time in type 1 spinal muscular atrophy (SMA), the most severe form of the disease, is significantly longer in children born between 1995 and 2006 than for those born between 1980 and 1994, say researchers at Columbia University in New York and Indiana University in Indianapolis.

Maryam Oskoui, now at the Montreal Neurological Institute, together with Petra Kaufmann and Darryl De Vivo, both co-directors of the MDA clinic at Columbia, with colleagues there and at IU, analyzed treatment and survival data for 143 children with type 1 SMA from the International SMA Patient Registry. They published their findings in the Nov. 13 issue of Neurology.

The researchers say the improved survival time is due to more widespread use of noninvasive assisted ventilation, cough assist devices, and gastrostomy tube feeding, as well as to a change in attitude about aggressive treatment of children with severe SMA because of increased optimism about future treatments.

The probability of survival to age 2 for children with an SMA1 diagnosis born between 1980 and 1994 was 30. 8 percent. For children with this same diagnosis born between 1995 and 2006, the likelihood of surviving to age 2 was 73.9 percent. Surviving to age 4 for the group born between 1980 and 1994 had a probability of 26. 2 percent, while for those born between 1995 and 2006, the probability was 65.1 percent.

The authors note that the new

findings should affect the way doctors counsel parents of children with SMA1 and should affect the plans parents make for their children, many of whom eventually will start school.

They also note that it will be important to take into account the change in the “natural history” of SMA1 when planning clinical trials in this disease.

“Given the improvement of outcomes over time, it could be misleading to compare trial participants now to untreated patients in the past,” Kaufmann said, adding that the study underscores the need for controlled clinical trials, in which a group taking the test medication is compared to a current group taking a placebo.

The Cambridge, Mass., biotechnology company Genzyme has determined that treating patients with late-onset Pompe disease (also known as acid maltase deficiency) with the synthetic enzyme Myozyme for 18 months increased endurance and pulmonary function.

The company announced these results in a Dec. 13, 2007, press release.

The study involved 90 people with Pompe disease who were at least 8 years old, at eight sites in the United States and Europe. Participants received either Myozyme, an enzyme designed to compensate for a deficiency of acid maltase (also known as acid alpha-glucosidase), or a placebo (inactive substance) by intravenous infusion. MDA provided supplemental support for the trial.

After 18 months, participants treated with Myozyme increased the distance they could walk in six minutes by an average of about 30 meters (about 90 feet), while those in the placebo group showed no improvement from their baseline measurement.

A respiratory measurement known as forced vital capacity increased by 1 percent in the Myozyme-treated group, while it declined by approximately 3 percent in the placebo-treated patients.

The safety of Myozyme was found to be similar to that of an intravenously infused placebo.