Our research journey began at the
University of Cambridge asking the question: how do neurons protect themselves
from Alzheimer's Disease?
What we found, across multiple biological levels, was the importance of the one-carbon metabolic pathway,
a key pathway in cellular energy. Neurons under stress upregulate this cycle
to protect themselves from the damage caused by Alzheimer's1,2,3.
OneCarbon was created to leverage this finding into something that could help
people in a way that was safe, effective, and accessible.
We discovered that bacteria in the gut produce molecules (metabolites) that can enhance
one-carbon metabolism. We used this knowledge to evolve 1C-01, a probiotic "living pharmacy"
that continually produces one-carbon metabolites.
We are still investigating potential benefits of 1C-01. 1C-01 is a probiotic which has not been MHRA-approved to be effective
against Alzheimer's, or any other, disease. Your participation in our research will help us reach our results faster.
Join our trial, PROFILE, to be part of OneCarbon's research towards Alzheimer's prevention.
A selection of published, peer-reviewed papers from our team and
independent scientists demonstrating the research supporting 1C-01.
Here you can find the papers, the authors, and a brief summary outlining
the paper's relevance to our research.
| Publication | Author(s) | Date | Summary | |
|---|---|---|---|---|
| Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models | Yu Y., Chen C.Z., Celardo I., Tan B.W.Z., Hurcomb J.D., Leal N.S., Popovic R., Loh S.H.Y., Martins L.M. | 2024 | View Here, we found that a specific mitochondrial process called one-carbon metabolism is disrupted in Alzheimer's disease. Boosting this pathway genetically or by supplementing with folinic acid improved mitochondrial function in both flies and cells. Human data also showed that genes involved in this pathway affect AD risk, suggesting a new treatment direction. | |
| Mitochondrial one-carbon metabolism and Alzheimer's disease | Yu Y., Martins L.M. | 2024 | View Multiple hallmarks of Alzheimer's disease — including amyloid-β accumulation, tau pathology, and age-related oxidative damage — converge on mitochondrial dysfunction, linked to impaired one-carbon metabolism. Five key cellular processes disrupted in AD (redox balance, NAD⁺ availability, mitochondrial function, genome stability, and DNA methylation) are all connected to the one-carbon pathway. SAM, the brain's primary methyl donor and a product of one-carbon metabolism, is severely depleted in AD brains. Enhancing mitochondrial one-carbon metabolism — through folate, folinic acid, or probiotic-based delivery — represents a viable therapeutic strategy for delaying the onset and progression of Alzheimer's disease. | |
| Blocking dPerk in the intestine suppresses neurodegeneration in a Drosophila model of Parkinson's disease | Popovic R., Mukherjee A., Leal N.S., Morris L., Yu Y., Loh S.H.Y., Martins L.M. | 2023 | View Using PINK1-mutant flies as a Parkinson's model, this study showed that sustained activation of the stress kinase dPerk in intestinal cells causes mitochondrial dysfunction, cell death, and reduced lifespan. Crucially, silencing dPerk specifically in the gut — without touching the brain — was sufficient to rescue dopaminergic neuron loss and restore motor function. The findings add mechanistic weight to the idea that gut dysfunction can drive neurodegeneration, and that interrupting this gut-to-brain stress signal is a viable neuroprotective strategy. | |
| Parp mutations protect from mitochondrial toxicity in Alzheimer's disease | Yu Y., Fedele G., Celardo I., Loh S.H.Y., Martins L.M. | 2021 | View We analysed the metabolomic changes in a fly model of AD and identified a decrease of metabolites associated with nicotinamide metabolism, which is critical for mitochondrial function in neurons. We used combined results in flies and humans to show that increasing the bioavailability of NAD+ is neuroprotective. | |
| One-Carbon Metabolism and Alzheimer's Disease: Focus on Epigenetics | Coppedè F. | 2010 | View AD patients consistently show reduced plasma folate, elevated homocysteine, and depleted SAM — the brain's primary methyl donor. When 1C metabolism is disrupted, impaired DNA methylation epigenetically dysregulates key AD-related genes, including PSEN1. Both animal models and human cell cultures support this as a meaningful contributor to amyloid-β production and AD pathology. | |
| Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease | Seshadri S. et al. | 2002 | View This Framingham Study cohort of over 1,000 adults found that elevated plasma homocysteine — a direct marker of impaired 1C metabolism — is a strong independent risk factor for AD. Every 5 µmol/L rise in homocysteine corresponded to a 40% increase in dementia risk. It remains one of the most cited pieces of population-level evidence linking 1C dysfunction to AD. |