Promising Results for Kearns-Sayre Syndrome of First in Man Treatment by Mitochondrial Augmentation Therapy (457)

Objective: To test the efficacy of Mitochondrial Augmentation Therapy (MAT) to improve physiological and metabolic status of a patient with Kearns-Sayre syndrome (KSS) Background: KSS is defined as progressive retinitis pigmentosa and external ophthalmoplegia occurring at childhood due to de-novo mtDNA deletions. Other systems may be involved over time including hearing, heart, central nervous system, skeletal muscles, endocrine glands and kidneys. There is no available treatment for KSS. Previous studies have shown that isolated mitochondria can re-enter cells and cells can transfer mitochondria to neighboring cells. MAT uses autologous CD34+ hematopoietic stem cells of the recipient enriched with normal mitochondria from his mother. Previous compassionate treatments of patients with Pearson disease demonstrated positive results. Design/Methods: A 14 year old girl with KSS with a known mtDNA deletion treated with MAT under IRB-approved compassionate use. Maternal mitochondria (confirmed non-deleted) were harvested from peripheral blood. Patient underwent leukapheresis and positively selected CD34+ cells were augmented with maternal mitochondria prior to infusion (2×10^6 cells/kg). The patient was followed for clinical and metabolic parameters 7 months after treatment. Results: There was a marked improvement in her function over 7 months. At base line she weighed 19 kg, she had only light/dark perception, she could not sit, walk or express words and had 1–2 seizures a week. Seven months after treatment, she had improved appetite and gained 3.6 kg. She could reach to 2 cm2 objects, sit independently, walk with an aid and express herself in short sentences. Her seizures resolved 4 months after treatment. Her normalized functional score on the International Pediatric Mitochondrial Disease Score improved from 91% to 57%. The ATP content of the peripheral blood lymphocytes increased. Conclusions: MAT treatment has markedly improved neurological and function and metabolic tests 7 months after treatment. It is a promising start for a potential therapy for KSS. Disclosure: Dr. Bar Yosef has nothing to disclose. Dr. Jacoby has nothing to disclose. Dr. Gruber has nothing to disclose. Dr. Varda-Bloom has nothing to disclose. Dr. Azaria has nothing to disclose. Dr. Eisenstein has nothing to disclose. Dr. Barak has nothing to disclose. Dr. Ahonniska-Assa has nothing to disclose. Dr. Anikster has nothing to disclose. Dr. Toren has nothing to disclose.