In Vitro Study on the Response of Fibroblast Cellular Respiration to Lipoic acid, Thiamine and Carnitine in Patients with Dihydrolipoyl Dehydrogenase Deficiency
Fatma A. Al-Jasmi*, Thachillath Pramathan, Hager Kowash and Abdul-Kader Souid
Department of Pediatrics, United Arab Emirates University, College of Medicine and Health Sciences, P.O. Box 17666, Al Ain, United Arab Emirates
- *Corresponding Author:
- Fatma A. Al-Jasmi
Department of Pediatrics
United Arab Emirates University
College of Medicine and Health Sciences
P.O. Box 17666
Al Ain, United Arab Emirates
E-mail: [email protected]
Received date: March 11, 2016; Accepted date: May 05, 2016; Published date: May 10, 2016
Citation: Al-Jasmi F, Pramathan T, Kowash H, Souid AK (2016) In Vitro Study on the Response of Fibroblast Cellular Respiration to Lipoic acid, Thiamine and Carnitine in Patients with Dihydrolipoyl Dehydrogenase Deficiency. J Mol Genet Med 10:214. doi:10.4172/1747-0862.1000214
Copyright: © 2016 Al-Jasmi FA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objectives: This study examined in vitro responses of fibroblast cellular respiration to lipoic acid, thiamine and carnitine in patients with dihydrolipoyl dehydrogenase (DLD) deficiency. This disorder impairs cellular bioenergetics and these compounds are used to improve clinical manifestations of the disease. The study aimed to utilize mitochondrial O2 consumption as a surrogate biomarker for examining cellular responses to metabolic therapies.
Methods: Cultured fibroblasts from three patients were treated with therapeutic concentrations of the compounds for 24 hours. Cells were then harvested and processed for measuring respiration using phosphorescence oxygen analyzer. Patients 1 and 2 were severely symptomatic infants with homozygous c.1436A>T mutation in the DLD gene. Patient-3 was a mildly symptomatic adolescent with homozygous c.685G>T mutation.
Results: The rate of respiration (mean ± SD, n=6, μM O2 min-1/107 cells) in fibroblasts from a normal infant was 9.3 ± 1.6, in fibroblasts from Patient-1 was 5.1 ± 0.9 (p=0.001), in fibroblasts from Patient-2 was 7.4 ± 1.4 (p=0.051), and in fibroblasts from Patient-3 was 10.3 ± 3.3 (p=0.836). In normal fibroblasts, respiration decreased by the thiamine (p=0.012) and carnitine (p=0.023) treatments. In Patient-1, respiration increased by the lipoic acid (p<0.002), thiamine (p<0.001), and carnitine (p=0.018) treatments; this patient clinically responded to thiamine. In Patient-2, respiration decreased by the thiamine (p=0.026) and carnitine (p=0.008) treatments; this patient did not respond to these drugs. In Patient-3, respiration increased by the carnitine (p=0.012) treatment; the patient clinically responded to carnitine.
Conclusions: The results show cellular respiration is a suitable biomarker for the disease. The significance of using this tool to assess responses to therapies requires further studies.