Detection of frataxin in blood samples, using an EIA: development and set up

VARELA, CAROLINA; PIKIELNY, RALPH; FARAJ, SANTIAGO; FERRARI, ALEJANDRO; BALBI, NOELIA; SANTOS, JAVIER

C.A.B.A.

Congreso; III congreso Internacional de Medicina Traslacional, Fac. De Farmacia y Bioquímica, UBA; 2016

IMBS - Argentina / Alemania

Introduction: Friedreich's Ataxia (FRDA) is a rare disease, with an prevalence of 1/50.000. FRDA is the most prevalent autosomic recesive ataxia world wide, and its cause is the mutation of both alleles of the gene that encodes for a mitochondrial protein named frataxin, which is associated to the assembly of iron-sulphur clusters on other mitochondrial proteins. The most frequent mutations (95-96% of individuals with FRDA) are the expansion of a GAA triplet in the first intron of both alleles of the frataxin gene, and the result is a decrease in the transcription rate of the gene, with the consequent reduction in the frataxin protein levels. The number of GAA repeats varies notably, ranging from a few to thousands. The remaining 4-5% are compound heterocygotes, which possess a GAA expansion in one of the alleles, combined with a point mutation in the other. Point mutations are varied, and have different effects depending on their possition, some of them also leading to decreased levels of mature frataxin protein. Regarding FRDA treatment, one of the most attractive perspectives seems to be the promotion of the increase in frataxin levels, augmenting the transcription rate, impeding is degradation or administering exogenous variants. In consequence, the development of methods for measuring fratax in biological samples becomes a priority for diagnosis, but also as a tool for monitoring future therapies.Results: The assay was performed on 20 individuals without FRDA signs, and 33 individuals with FRDA signs and genetic diagnosis of FRDA. The results allow to affirm that the EIA has the ability to distinguish among FRDA and non-FRDA individuals. Therefore, this assay comprises a fast, low-cost tool for the diagnosis of FRDA, and also for the follow-up during future FRDA therapies.Conclusion and discussion: The development of this method could be an significant tool to a complementary diagnosis of FRDA disease. Also it could be useful for the monitoring in reasearch and applications of futures therapies.