Milan, Italy, July 08 — Genespire, in collaboration with researchers at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), has today announced the publication of preclinical data supporting the potential of its liver-directed immune-shielded lentiviral gene therapy approach to treat methylmalonic acidemia (MMA), a severe inherited metabolic disorder. The findings, published in the Journal of Hepatology, show that a single systemic administration of a lentiviral vector encoding the MMUT gene led to sustained improvements in disease features in a validated mouse model of MMA, with effects lasting for the average lifespan of laboratory mice. Since the mice were treated when young, the study supports the durability of the gene therapy through postnatal growth and maturation of the liver. MMA is caused by a deficiency of methylmalonyl-CoA mutase, an enzyme that plays a critical role in the body’s metabolism of food. Its absence results in the accumulation of toxic metabolites that lead to recurrent metabolic crises, growth failure, neurological impairment, and multi-organ damage. In the study, researchers also treated mice with a dose containing an optimized MMUT transgene, thereby improving therapeutic efficacy. In the same mouse model of MMA, this version exhibited a dose-dependent improvement of metabolomic biomarkers, with gene transfer efficiency exceeding 80% of the liver. The study also highlights that genetically corrected cells in the liver may, over time, replace the diseased ones, suggesting that therapeutic efficacy may progressively improve even when starting at lower initial doses. “Together, these findings indicate that Genespire is on a clear path towards the long-term correction of metabolic diseases which impact the liver and other organs,” said Lucia Faccio, CEO of Genespire. “We believe our approach has the potential to translate into human health in the form of a single-administration treatment for patients with MMA, and are committed to continuing our efforts in bringing our lead asset for MMA, GENE202, to the clinic. We would like to extend our gratitude to everyone involved in the research project, especially those at the SR-TIGET.” “We are confident that this study, together with other previous studies from our group at SR-TIGET, provides a comprehensive pre-clinical data package enabling the initiation of clinical testing in pediatric patients affected by MMA” concludes Dr Alessio Cantore, group leader at SR-TIGET and Associate Professor at Vita-Salute San Raffaele University, who supervised and coordinated the study and signed it as senior author.