While there seems to be no firmly established mechanism by which urolithin A acts to modestly improve mitochondrial function, it seems presumed that this (and a number of other compounds, such as mitoQ) largely function via improving the operation of mitophagy. Mitophagy, mitochondrially targeted autophagy, is a maintenance process that removes damaged and worn mitochondria. Too little of that and the mitochondrial population in a cell become incrementally more dysfunctional. Impaired mitophagy and mitochondrial dysfunction are features of aging, while improved autophagy is a feature of cell stress responses and many interventions known to modestly slow aging in animal studies.
Vandria is one of a number of companies attempting to make therapies for age-related conditions based on novel modifications of established autophagy or mitophagy promoting compounds. Here, Vandria is noted to have started an initial clinical trial for a urolithin A derivative. So far, efforts in this direction have failed to improve on calorie restriction, and only the rapalogs have done better in some aspects than exercise. It remains to be seen as to how this line of work will fare. Certainly, the original urolithin A compound isn’t all that impressive in animal studies.
Vandria SA, a company at the vanguard of mitochondrial therapeutics developing first-in-class small molecule mitophagy inducers, today announces that the first subjects have been dosed in its first-in-human clinical trial of its lead Central Nervous System (CNS) compound VNA-318. Readout of this combined single and multiple ascending dose trial is expected in the summer of 2025.
VNA-318 is an orally available first-in-class small molecule against a novel target to rejuvenate cells and treat age-related diseases through the induction of mitophagy. The target has strong genetic links to several human diseases including Alzheimer’s disease. It has a dual mode of action with an immediate improvement of memory, learning, and cognitive function, paired with long-term disease-modifying effects such as reduced neuroinflammation, less toxic protein aggregation, and improved mitochondrial function, as shown in pre-clinical models of Alzheimer’s and Parkinson’s disease. Toxicity studies have demonstrated VNA-318 has a wide safety window. A composition of matter patent covering VNA-318 and other compounds has been issued by the US Patent Office.
This Phase 1 randomized, double-blind trial is a combined single and multiple ascending dose trial of VNA-318, designed to assess safety, tolerability, pharmacokinetic, and pharmacodynamic parameters in healthy male subjects.
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