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Ultimate Medicine Publishes Data in Nature Aging Showing Novel Gut-Brain Pathway Metabolite Involved in Age-Related Cognitive Decline

Forms basis for therapeutic and diagnostic development for age-related memory loss

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Ultimate Medicine, a drug discovery company leveraging in vivo multiomics, announced today publication in Nature Aging of data showing that the microbiota-related metabolite δ-valerobetaine (delta-valerobetaine) plays a role in neurocognitive ability. Using delta-valerobetaine as a target, Ultimate Medicine is developing therapeutic and diagnostic approaches to help detect and treat age-related memory loss.

“Evidence has been building on the role that the microbiota plays in many diseases, including the significant impact seen on brain function and behavior. These effects are mediated through the gut-brain axis, a complex network of immune, neuroendocrine and vagal pathways,” explained Dr. Thomas Blank from the Institute of Neuropathology, University of Freiburg (Germany). “Working with the analytics expertise of Ultimate Medicine, we have now identified a specific metabolite, delta-valerobetaine, found within this biological network that is closely linked to age-related memory loss. We have first strong evidence that delta-valerobetaine warrants further investigation, particularly as it is found to be age dependent in increasing levels in human serum and cerebrospinal fluid. There is even a difference in the level between patients with dementia and normally aged people.”

In the Nature Aging paper, titled “Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline,” scientists from Ultimate Medicine and the University of Freiburg showed that fecal microbiota transplantation (FMT) from young mice into old mice was able to restore their cognitive abilities. Subsequent metabolomics using serum and brain samples identified delta-valerobetaine, levels of which increased as mice aged. When delta-valerobetaine is injected into young mice, learning and memory performance was found to be similar to that seen in old mice.

To explore the impact of delta-valerobetaine directly in the brain, the researchers conducted in vivo electrophysiological recordings from the prefrontal cortex of young mice. When injected with delta-valerobetaine, these recordings showed a definitive change in action potential synchronization, representing a critical process underlying memory formation.

“The discovery of delta-valerobetaine, a novel target that we are now leveraging for therapeutic applications as part of our UM 001 program, shows the power of our in vivo multiomics approach in discovering and validating targets and biological pathways,” said Dr. Antal Szalay, CEO and Founder of Ultimate Medicine. “We believe this approach will lead to more novel insights based on biological data, resulting in more productive drug development, with only those compounds with a better chance of success moving through preclinical evaluation. We are now in the process of raising funds to further validate our biomarkers and forward integrate our first lead program.”

 

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