AI Article Synopsis

  • Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) often suffer from serious multisystemic diseases like Pearson syndrome in childhood or Kearns-Sayre syndrome later on, and there's currently no effective treatment available.
  • A new approach called mitochondrial augmentation therapy (MAT) was tested on six patients with SLSMDs, where their own hematopoietic cells were infused with healthy maternal mitochondria.
  • The treatment showed safety, decreased harmful mtDNA levels in four patients, and increased mtDNA content in all six, alongside some improvements in aerobic function and quality of life measured by caregivers, suggesting a need for further clinical trials.

Article Abstract

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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Source
http://dx.doi.org/10.1126/scitranslmed.abo3724DOI Listing

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