Inherited Metabolic Disorders
Inherited metabolic disorders refer to different types of medical conditions caused by genetic defects that impact metabolism primarily within hepatic cells in the liver. There are hundreds of inherited metabolic disorders, caused by different genetic defects. These often lead to accumulation of substances which are toxic or interfere with normal cellular/organ function, or to the effects of reduced ability to synthesize essential compounds. These diseases can be life threatening or strongly debilitating for the people suffering from them, and although some of these diseases can be treated by diet or by enzyme replacement therapies, many of them remain a high unmet medical need, and often progress to organ failure, and death, with a strong impact on life expectancy.
In order to tackle such genetic metabolic diseases, Genespire builds on a novel lentiviral vector technology, the “immune-shielded LV” developed by the group of Pr. Luigi Naldini and Dr. Alessio Cantore at SR-Tiget, to develop off-the-shelf liver-directed in vivo gene therapies. Lentiviral vectors offer the advantage of a stable, long term expression of the corrective genes, therefore allowing to tackle diseases with early onset, in patients where the liver is still growing, and where other approaches may lead to suboptimal results. The approach selected by Genespire allows for long term and stable hepatocyte-specific expression of the “corrective” transgene. In addition, our platform technology relies, amongst other features, on proprietary technologies of micro-RNA regulated expression of the transgene to avoid off target expression in antigen expressing cells, and of MHC-free packaging cell lines for reduced immunogenicity of the administered vector. We therefore anticipate that our approach will lead to an improved safety profile and an increased efficacy in tackling inherited metabolic diseases.