A team of researchers at NeuroVive Pharmaceuticals developed a new pharmacological strategy that could potentially be used to treat mitochondrial disease.
In some types of mitochondrial disease, such as Leigh’s syndrome and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), a group of mitochondrial enzymes called mitochondrial complex I is defective. This complex is essential to make succinate, an intermediate molecule in the production of energy within the mitochondria. When the complex does not work, the entire energy production cycle falls apart.
One strategy to avoid this problem would be to deliver succinate into the mitochondria to bypass this step in energy production. However, succinate is not membrane permeable and cannot be absorbed into the cell.
In this study, researchers used a prodrug technology to modify succinate and make it membrane permeable. This way, it can be used by mitochondria to produce energy inside the cells. A prodrug is an inactive compound that becomes activated when it enters the cells and its chemical structure is altered.
Researchers treated cells isolated from patients with Leigh’s syndrome with succinate prodrugs and saw that the energy production could be increased. The results were published in the leading scientific journal Nature Communications in an article titled “Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency.”
“The Nature Communications publication is a significant achievement for our team involved in mitochondrial disease research aiming at developing new therapeutic options for these serious diseases and reinforces the strength of our partnerships in advancing the research,” said Dr. Eskil Elmér, chief scientific officer at NeuroVive and senior author of the study, in a press release.
The prodrugs are not yet available to be used to treat mitochondrial disease in humans because they are not stable enough in the blood. The team is currently working on developing a series of new succinate prodrugs with increased stability as part of NeuroVive’s NVP015 research program. The company is testing these new compounds in different experimental models.
“We are very excited to see continued development of these drugs aiming at offering mitochondrial disease patients a beneficial treatment,” Elmér said.
NeuroVive is a Swedish company developing new drug candidates to treat mitochondrial disease. The NVP015 research program was developed by Elmér and colleagues to produce cell-permeable prodrugs of succinate.