Mus musculus Transcriptome or Gene expression

Huntington''s Disease (HD) is chronic neurodegenerative disease. HD is caused by a defect in the Huntingtin (Htt) gene. As a consequence of this defect, mutated proteins are produced in the brain. These mutated proteins accumulate in the brain and destroy the neurons, causing loss of their functions. So far, the treatment of the disease is only palliative. Gene therapy is a technique for correcting defective or missing genes that otherwise cause a disease. This can be done by inserting a functional copy of the gene into the appropriate cells of the patient, to restore body function. The aim of the project was to develop the gene therapy against Huntington''s Disease by stimulation of the maintenance and survival of neurons by neurotrophic factors, like glial cell line-derived neurotrophic factor (GDNF). GDNF is one of the most potent neurotrophic factors in the brain and its efficacy have been proved in several pre-clinical studies.The proof of concept studies aiming to reveal molecular changes of the cells subjected to regulated GDNF gene therapy have been performed in the in HD mouse models (BACHD). The global molecular state of the striatum and cortex cells of BACHD mice that have been challenged with the AAV viral vectors delivering the intended therapeutic nucleic acid was monitored by means of gene expression analysis (RNAseq) using high-throughput DNA sequencing technology (NGS- next generation sequencing). Six groups of BACHD mice (including the control one) differing in the GDNF expression pattern were analyzed (for each group of animals 3 biological replicates were used for RNAseq).This project was supported by Eurostar grant E!7900 HD-gene therapy and National Centre for Research and Development (Poland) grant no E7900/19/NCBR/2014.