Decifrar a Neuropatologia e os Mecanismos da Doença numa Nova Leucodistrofia Causada por Mutações no Slc44a1

For this project – Leuko44a1- our objectives are to: 1- Establish the impact of Slc44a1 deficiency on Central Nervous System Myelin and Myelination. Employing innovative mouse models featuring targeted Slc44a1 defects, we aim to dissect and elucidate the ramifications of Slc44a1 deficiency within the central nervous system. Building upon our initial discoveries, our research will delve into the repercussions of Slc44a1 loss on myelin integrity and the intricate process of myelination, essential for optimal CNS functionality. 2- Unraveling Proteomic and Metabolic Alterations in Slc44a1 Knockout Mice. We will conduct comprehensive proteomic and lipidomic analyses on affected target tissues to deepen comprehension of Slc44a1's role, neuropathological manifestations, and underlying disease mechanisms. Through these analyses, we aim to unveil cellular pathways perturbed by the absence of Slc44a1, shedding light on its functional significance and potential therapeutic avenues. 3- Exploring the Therapeutic Efficacy of AAV-Mediated Gene Therapy in Alleviating Neuropathological Deficits in Slc44a1 Knockout Mice. Serving as a proof-of-principle and within the context of pre-clinical efforts to develop a potential therapy, we will determine if adeno-associated viral (AAV)-mediated gene therapy can rescue the phenotype and neuropathology of Slc44a1 mutant mice. 4- Amplifying understanding: development of strategies for rare disease diagnosis, awareness, communication, and dissemination. To effectively foster collaboration among researchers, clinicians, and patients, we have developed a strategic plan encompassing various initiatives to enhance awareness, communication, and dissemination of the findings generated throughout the execution of Leuko44a1.