A phase 1 trial of @entity10891 in XXXX .

@entity1 @entity2227 @entity4574 @entity10891 @entity4681 @entity746 @entity2057
BACKGROUND: Severe @entity2057 ( @entity2057 ) ( @entity4574 , @entity2057 ) is a disease of the motor neuron characterized by onset before 6 months of age, failure ever to achieve sitting without support, and a life expectancy of 2 years or less. There is no known treatment for @entity2057 , and, until recently, no therapeutic trials have been attempted. There is reason to believe that @entity2227 , an excitatory neurotransmitter, enhances programmed cell death of anterior horn cells. @entity10891 , a @entity2227 inhibitor, has been shown to slow the rate of decline in @entity1 with @entity746 , another form of @entity4681 . OBJECTIVES: To determine whether a @entity2227 inhibitor might be tolerated by @entity1 with @entity2057 and, furthermore, whether this medication could have a positive effect on life expectancy. DESIGN: Subjects with homozygous deletions of the survival motor neuron gene were recruited from pediatric neuromuscular clinics and randomized in a 2:1 ratio, 2 @entity10891 to 1 placebo. Neurologic examination was performed at the first visit by one of the investigators. Complete blood count, hepatic and renal screens, and urinalysis were performed at baseline, 2 weeks, 1 month, 2 months, 3 months, 6 months, and 9 months after drug or placebo was started. An electrocardiogram was done at baseline, 3 months, 6 months, and 12 months. Treatment was stopped after 9 months, and blood work was repeated at 12 months. Treatment was reinstituted at 1 year if requested by the parents. The enrollment goal was 30 @entity1 ; however, support from the pharmaceutical company was withdrawn when Rhone-Poulenc Rorer was taken over by Aventis. The investigational review boards of the participating centers approved the protocol and consent forms. RESULTS: Seven @entity1 received @entity10891 and 3 received placebo medication. All 3 @entity1 in the placebo group died (mean age, 9 months). Three of 7 who received active drug are still living at ages 513 years, 4 years, and 30 months. None of the 10 subjects experienced adverse effects or changes in laboratory test results. None showed any change in motor abilities. CONCLUSIONS: @entity10891 appears to be safe in young @entity1 . This was a limited study with insufficient power to show a difference between the 2 groups. Because there is a suggestion of possible benefit in treated subjects, we recommend further study of @entity10891 in pediatric @entity1 with @entity2057 .
