title: Plasma circulating cell-free mitochondrial DNA in the assessment of Friedreich's ataxia.
abstract: Friedreich's ataxia (FRDA) is one of the most devastating childhood onset neurodegenerative disease affecting multiple organs in the course of progression. FRDA is associated with mitochondrial dysfunction due to deficit in a nuclear encoded mitochondrial protein, frataxin. Identification of disease-specific biomarker for monitoring the severity remains to be a challenging topic. This study was aimed to identify whether circulating cell-free nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in blood plasma can be a potential biomarker for FRDA. Clinical information was assessed using International Cooperative Ataxia Rating Scale and the disease was confirmed using Long-range PCR for GAA repeat expansion within the gene encoding frataxin. The frataxin expression was measured using Western blot. Plasma nDNA and mtDNA levels were quantified by Multiplex real-time PCR. The major observation is that the levels of nDNA found to be increased, whereas mtDNA levels were reduced significantly in the plasma of FRDA patients (n=21) as compared to healthy controls (n=21). Further, plasma mtDNA levels showed high sensitivity (90%) and specificity (76%) in distinguishing from healthy controls with optimal cutoff indicated at 4.1×10(5)GE/mL. Interestingly, a small group of follow-up patients (n=9) on intervention with, a nutrient supplement, omega-3 fatty acid (a known enhancer of mitochondrial metabolism) displayed a significant improvement in the levels of plasma mtDNA, supporting our hypothesis that plasma mtDNA can be a potential monitoring or prognosis biomarker for FRDA.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: subra1111@gmail.com.
authors.forename: Subrahamanyam
authors.initials: S
authors.lastname: Dantham
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: achalsrivastava@hotmail.com.
authors.forename: Achal K
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: Paediatrics Neurology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: sheffaligulati@gmail.com.
authors.forename: Sheffali
authors.initials: S
authors.lastname: Gulati
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. Electronic address: rajeswari3011@hotmail.com.
authors.forename: Moganty R
authors.initials: MR
authors.lastname: Rajeswari
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002648:Child; D004272:DNA, Mitochondrial / Q000097:blood*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005621:Friedreich Ataxia / Q000097:blood* / Q000178:diet therapy / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins / Q000097:blood / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult; D000096923:Frataxin
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D015525:Fatty Acids, Omega-3; D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Biomarker; Friedreich's ataxia; Mitochondrial DNA; Plasma cell-free nucleic acids