New Molecule PZL-A Shows Promise in Reversing Effects of Mitochondrial DNA Mutations

Scientists have discovered a novel molecule that could reverse the effects of mutations in mitochondrial DNA. This discovery may represent a significant advance in the treatment of POLG-related diseases. These diseases, caused by mutations in the POLG gene, lead to a variety of symptoms ranging from mild muscle weakness to severe neurological disorders. The research, published in the journal Nature, shows that the molecule PZL-A is able to significantly improve the function of the POLG protein in laboratory tests. The POLG gene encodes an essential protein in the mitochondria, the power plants of cells, responsible for the replication and repair of mitochondrial DNA. Mutations in this gene can lead to an accumulation of harmful mutations in mitochondrial DNA, impairing the energy production of cells. The researchers discovered that the molecule PZL-A is able to increase the stability of the POLG protein and thus improve its ability to repair DNA. Clinical trials are currently underway to test the safety and efficacy of the molecule in humans. These studies are being conducted by Pretzel Therapeutics, a company founded by some of the authors of the study. The initial tests focus on the safety of the molecule in healthy subjects, before it is tested in patients with mitochondrial diseases next year. Treating POLG-related diseases poses a major challenge, as there are over 300 different mutations that can trigger these diseases. Previous approaches, such as gene therapy, have had limited success due to the large number of mutations. However, the new molecule could offer a universal solution by improving the function of the POLG protein regardless of the specific mutation. The researchers are optimistic that the molecule could be used not only for POLG-related diseases, but also for other diseases associated with depletion of mitochondrial DNA. These include age-related neurodegenerative diseases, which are also associated with reduced mitochondrial function. The discovery of PZL-A could therefore not only represent a breakthrough in the treatment of rare genetic diseases, but also open up new avenues for the treatment of age-related diseases. The coming years will show whether the molecule actually has the potential to revolutionize the treatment of these complex diseases.