Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34 + hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.

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Aim: To evaluate the reliability and validity of the PEDI in Hebrew (PEDI-H) in children with cerebral palsy (CP) using health care professionals' (HCP) and mothers' evaluations. Methods: The sample comprised 73 participants (40 males, 33 females) with CP. Two modes of PEDI-H administration were used: interview of the mothers by a social worker and HCP evaluation. PEDI-H reliability was examined by two modes: 1) internal consistency via Cronbach's alpha and 2) overall absolute agreement within subject reliability via intraclass correlation coefficient (ICC). Discriminative validity using collapsed strata of the Gross Motor Functional Classification System (GMFCS) (area under the curve = AUC) were examined for each of the PEDI-H sub-domains. Results: Participants' mean age was 8 years 8 months (standard deviation (SD) 2 years 10 months). The reliability of mothers' PEDI-H was good-to-excellent (Cronbach's alpha = 0.889-0.964, ICC = 0.845-0.938). The HCPs' reliability was excellent (Cronbach's alpha and ICCs > 0.90). The PEDI-H was also reliable in children with mild, moderate, and severe CP (GMFCS = I + II, III and IV + V, respectively), in younger (6-7 years) and older children (8-12 years), and in children with various CP distribution. Mothers and HCPs had low accuracy in Social-Function domains (AUC = 0.538-0.686) and moderate-to-high accuracy in Mobility and Self-Care domains (AUC = 0.887-0.967). PEDI-H was able to distinguish between children with various CP severities. Conclusion:The PEDI-H has good psychometric properties when administered by mothers and HCPs and can be used in older children with CP.