Molybdenum cofactor (Moco) is a compound that is little known but is essential for life. Children born without the ability to synthesize Moco die young. However, it has not been possible to create Moco supplements because the compound is so unstable. Now researchers say they have found a potential pathway that can make Moco stable and repair deficiency, by combining Moco with certain proteins in the nematode Caenorhabditis elegans.

Their study, “Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans,” is published in the journal Genes and Development.

The work was led by Gary Ruvkun, PhD, from the department of molecular biology at Massachusetts General Hospital (MGH) and the department of genetics at Harvard Medical School, and Ralf R. Mendel, PhD, a pioneer in Moco research at the Braunschweig University of Technology in Germany.

Moco deficiency is a rare condition characterized by brain dysfunction that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment.

“Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects,” the researchers wrote. “Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability.”

The researchers carried out studies in C. elegans that were engineered to be deficient in their ability to make Moco. C. elegans deficient in Moco also die very early in development. However, they can also ingest Moco from their diet. The research team observed that the worms could take in Moco as a range of purified Moco-protein complexes. These included complexes with proteins from bacteria, bread mold, green algae, and cow’s milk. Ingesting these complexes saved the Moco-deficient worms.

“The nematode C. elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution,” noted the investigators. “Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a C. elegans model of Moco deficiency.”

“We tested four proteins and all four were restorative in our nematode model. That’s very encouraging,” stated Kurt Warnhoff, PhD, an investigator in the department of molecular biology at MGH and the paper’s co-lead author. “We do not want to overstate our findings, especially as they relate to patients, but we are extremely excited about the therapeutic and fundamental implications of this work.”

Although future studies are needed before clinical application, this strategy may lead to potential treatments and hope for this rare, but devastating disease.