Robert D. Phair, PhD, co-founder and Chief Science Officer at Integrative Bioinformatics Inc. in Mountain View, CA was recently awarded an OMF research grant in collaboration with the CFS research team at the Stanford Genome Technology Center. The two groups have been working together for 20 months and now propose to test a new hypothesis for the etiology of ME/CFS, called the metabolic trap hypothesis.
Whole genome sequencing data obtained during the OMF-funded Severely Ill Patient Study (SIPS) provided the initial clue that damaging mutations in some genes are a common feature of the SIPS genomes. Some, but not all, of these mutations are common in the general population as well, so they are not causal, but they may represent a genetic predisposition to ME/CFS. Phair’s metabolic trap hypothesis emerged from a synthesis of published enzyme kinetics using mechanistic computational modeling.
The new OMF-funded work will test this hypothesis using stable isotope metabolic tracer experiments on cells from ME/CFS patients and healthy controls (managed and carried out by a senior life science professional at Stanford, Julie Wilhelmy), and expert mass spectrometry at the Stanford Metabolic Chemistry Analysis Center headed by another collaborator, Curt R. Fischer, PhD. Everyone involved is already working hard on experimental tests.
We should be able to test this hypothesis in a few months. It is exciting to us and should be to the patients because if correct would explain why most patients seem to be in a loop and never getting better. Also if right we have some ideas how we might treat. We hope it is right.