Project No. | lzp-2024/1-0382 |
Project coordinator | Latvian Institute of Organic Synthesis (LIOS) |
Project leader | Edgars Liepiņš (LIOS) |
Implementation period | 36 months (2025-2027) |
Total cost
| 300 000,00 EUR |
The metabolism of fatty acid (FA) within mitochondria and peroxisomes is pivotal for the functioning of vital organs such as the heart, muscles, and liver. Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism due to disruption of either mitochondrial β-oxidation or the acylcarnitine transport pathway. Despite early diagnosis and some effectiveness of dietary interventions, many FAOD patients continue to manifest symptoms, which underlines the need for additional individualized treatment strategies.
While elevated levels of long-chain acylcarnitines have served as diagnostic biomarkers for FAODs for over two decades, a therapeutic approach that would decrease long-chain acylcarnitine levels remains unexplored. The growing evidence suggests that long-chain acylcarnitines impair mitochondria functions and affect ion channels thus leading to energy deficiency and arrhythmias.
We have discovered new pharmacological means how to prevent long-chain acylcarnitine accumulation which pose new possible opportunities for FAOD management. The project will develop a treatment strategy to mitigate the risk of long-chain accumulation while preserving residual FA oxidation. Through preclinical investigations employing in vitro assays and animal models, we aim to validate the efficacy of reduced acylcarnitine synthesis rate in preventing and managing metabolic complications affecting muscle, liver, and cardiovascular systems in FAOD.
