A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism.

PURPOSE: To evaluate effectiveness of elamipretide in Barth syndrome (BTHS), a genetic condition of defects in TAZ, which causes abnormal cardiolipin on the inner mitochondrial membrane. METHODS: We performed a randomized, double-blind, placebo-controlled crossover trial followed by an open-label extension in BTHS to test the effect of elamipretide, a mitochondrial tetrapeptide that interacts with cardiolipin. In part 1, 12 subjects were randomized to 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm. Ten subjects continued on the open-label extension (part 2) of 40 mg per day of elamipretide, with eight subjects reaching 36 weeks. Primary endpoints were improvement on the 6-minute walk test (6MWT) and improvement on a BTHS Symptom Assessment (BTHS-SA) scale. RESULTS: In part 1 neither primary endpoint was met. At 36 weeks in part 2, there were significant improvements in 6MWT (+95.9 m, p = 0.024) and BTHS-SA (-2.1 points, p = 0.031). There were also significant improvements in secondary endpoints including knee extensor strength, patient global impression of symptoms, and some cardiac parameters. CONCLUSION: In this interventional clinical trial in BTHS, daily administration of elamipretide led to improvement in BTHS symptoms.

Physical Abilities and Mobility Scale: reliability and validity in children receiving inpatient rehabilitation for acquired brain injury.

OBJECTIVE: To investigate the psychometric properties of the Physical Abilities and Mobility Scale (PAMS) in children receiving inpatient rehabilitation for acquired brain injury (ABI). DESIGN: Admission and discharge PAMS item and total scores were evaluated. The WeeFIM was used as the criterion standard. A case study was used to illustrate the complementary nature of the PAMS and WeeFIM. SETTING: A single, free-standing, academically affiliated pediatric rehabilitation hospital. PARTICIPANTS: Children (N=107) aged 2 through 18 years receiving inpatient rehabilitation for ABI between March 2009 and March 2012. Forty-two additional children treated during this time were excluded because of missing PAMS data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Internal consistency was evaluated using Cronbach alpha. Interrater reliability was evaluated through overall agreement, Pearson correlations, and intraclass correlations. Construct validity was examined through exploratory factor analysis. Criterion validity was explored through correlations of PAMS overall and factor scores with WeeFIM total and subscale scores. Sensitivity to recovery was examined using paired t tests, examining differences between admission and discharge scores for each item and for the total score. RESULTS: Internal consistency and interrater reliability were high. Factor analysis revealed 2 factors: lower-level skills and higher-level mobility skills. Correlations with the WeeFIM ranged from moderate to very strong; total PAMS score most strongly correlated with the WeeFIM mobility subscore. Total PAMS score and each item score significantly increased between admission and discharge. CONCLUSIONS: The PAMS is a reliable and valid measure of progress during inpatient rehabilitation for children with ABI. By capturing fine-grain progress toward both lower-level and higher-level mobility skills, the PAMS complements the WeeFIM in assessing functional gains during the rehabilitation stay.