Preventionof the Leigh’s Syndrome
Preventionof the Leigh’s Syndrome
Leigh’sSyndrome is a genetic disorder and therefore it can only be preventedif nuclear genes are identified. If the biochemical alteration isthe only symptom detected, then prevention would be difficult. Thisis because the analysis of amniocytes and identifying of differentfibroblast mutation would be rather difficult.
Althoughefforts for prevention are still at the primary stages (Ciafaloni etal., 2003), it is emerging that the transplantation of the nucleusinto enucleated oocyte could just be an option to help preventmitochondrial diseases. This enables women to give birth to offspringwithout necessarily transmitting mutated DNA.
Thediagnosis of mtDNA at the prenatal level is challenging particularlyif historical typical elements and vital mtDNA heteroplasmy areinvolved. Additionally, options for prevention at the reproductivelevel include prenatal diagnosis (either CVB or amniocentesis), thedonation of egg and sperm, methods such as PGD which are aimed oprevent or limit transmission or generally undertaking an alternativeto pregnancy such as surrogate parenting (Van et al., 2001). All thisinformation should be made accessible to families who are affected bythe disease in order for them to make prudent reproductive choices.
However,advances in the prevention of mtDNA diseases have not progressed asfast as the ability to diagnose. For most patients with mtDNAdiseases, their therapy is generally restricted to symptomatic reliefas well as detecting symptoms which can be treated (Ciafaloni et al.,2003) these include cardiac diseases and epilepsy.
Fortunately,a recent study shows that a ubiquinone analog, idebenone is quitehelpful. Evident from tests done on animal models suggest that anincrease in mitochondrial biogenesis by use of certain drugs is quitepromising. This prevention method is likely to be more effective inpatients with a mild mtDNA disease (Van et al., 2001).
Recently,there has been proof that experiments conducted by use of humanzygotes abnormally fertilized. A similar technique involving thetransplant of the metaphase II spindle between oocytes which areunfertilized has led to live born rhesus monkeys.
Theeffectiveness of these techniques, however, depends on reducingmitochondrial transfer during the process of nuclear genometransplantation. The transfer of both pronuclear and metaphase IIspindle involve the fusing of a karyoplast with nuclear materialusually surrounded by a little cytoplasm which may probably containmitochondrion (Ciafaloni et al., 2003). Therefore, it is possible forthe affected mitochondria to be transferred to the offspring. Methods to reduce the karyoplast size have with time been fruitful inreducing this transfer in that there is little or no carryover of themtDNA.
Itis additionally essential to identify whether manipulations which areassociated with the transplantation of nuclear genome are harmful tothe development of the embryo. Information garnered from studies onmice show that the transfer of pronuclear goes along with ordinarydevelopment. Evidence from studies shows a 50% reduction in theembryos which develop the blastocyst stage (Ciafaloni et al., 2003).It should, however, be noted that studies done on zygotes abnormallyfertilized have one or three pronuclei which show sizeabledifferences in the constitution of chromosomes and have thus limitedthe capacity to develop.
Theeffect of the transfer of metaphase II spindle on the development ofan embryo is restricted to studies done on rhesus monkeys whichsuggest that the methodology of spindle transfer is quite compatiblewith the production of a normal offspring. Presently, PGDavailability and the imminent possibility to transfer the nucleushighlight a profound level in the prevention of mitochondrialdiseases such as Leigh’s Syndrome.
Ciafaloni,E., Santorelli, F. M., Shanske, S., Deonna, T., Roussel, E., Janzer,C., & DiMauro, S. (2003). Maternally Inherited LeighSyndrome. TheJournal of pediatrics, 122(3),419-422.
Van,C. R., Lombes, A., Darryl, C., Chi, T. L., Dodson, W. E., Rothman,S., & Habib, A. (2001). Cytochrome Oxidase-Associated LeighSyndrome: Phenotypic Features and Pathogenetic Speculations. Journalof the neurological sciences, 104(1),97-111.