Periodic Reporting for period 1 - MITOPOMPE (Targeting mitochondrial defects and oxidative stress in Pompe Disease: from pathogenesis to therapy)
Reporting period: 2019-01-01 to 2020-12-31
MITOPOMPE project aims at better understanding and developing novel treatments to a rare disease named as Pompe disease. Pompe disease belongs to the group of Lysosomal Storage Disorders (LSDs) and has an overall incidence of 1:40,000 births. The full understanding of pathophysiology of Pompe disease is missing. Furthermore, the currently available treatment (Enzyme Replacement Therapy) is very costly and far from being effective. Therefore developing novel treatments such as ‘gene therapy’ is vital for these patients. MITOPOMPE project aims at understand the bioenergetic defects observed in the disease And to develop gene therapy based solutions to overcome the bioenergetic defects. These efforts can contribute to better optimize the currently ongoing gene therapy based therapeutics.
This project involved using mice models of Pompe disease to discover the mechanisms of involvement of mitochondria (metabolic hubs of the cells). We have uncovered mechanisms why bioenergetic defects present in Pompe disease. We further applied a gene therapy based approach to treat this disease which is currently in clinical trial. In summary, the results obtained within MITOPOMPE project were included in several high impact publications such as in the journals of Molecular Therapy (official journal of American Society of Gene and Cell Therapy) and EBioMedicine (The Lancet Press).
We have further worked on developing novel gene therapy solutions. Some of data collected showed importance of analyzing and targeting bioenergetic defects. For example, we observed slight and limited amelioration of muscle function upon correction of the oxidative stress, another hallmark of Pompe disease. Further experiments may be need to discover the full potential of such approaches. These data may be included foe publications in the future.
We have further worked on developing novel gene therapy solutions. Some of data collected showed importance of analyzing and targeting bioenergetic defects. For example, we observed slight and limited amelioration of muscle function upon correction of the oxidative stress, another hallmark of Pompe disease. Further experiments may be need to discover the full potential of such approaches. These data may be included foe publications in the future.
The data obtained within MITOPOMPE project was disseminated not only by scientific publications but also at scientific meetings. These data was also discussed with some of the high profile scientists and clinicians in the field of Pompe disease and gene therapy. The currently available therapy option (Enzyme Replacement Therapy) if inefficient, costly and requires biweekly visit to the hospital. It is important to highlight that MITOPOMPE project contributed to the efforts of gene therapy solutions for Pompe disease which is currently in clinical trials and can offer one-time solution. These treatments can not only extend the life of Pompe disease patients but also increase the quality of the lives of patients.