In CDG cases, the conversion from polyprenol to dolichol is blocked by a mutation in the SRD5A3 gene. "The mutation is inherited recessively," said Gleeson. "Both parents must pass along a mutated copy, which is why you don't see it so much in the US. However, in the Middle East, where marriage of cousins is common, these diseases are much more prevalent."

Identifying the blockage, Gleeson said, pointed to a possible treatment.

"The key was identifying the enzyme's role in producing dolichol. This is the basic step that is blocked in our patients, and the disease is the result. Our idea is that if you feed these patients dolichol, that might just treat the condition. It would be similar to giving insulin to diabetics. It's a simple solution, but one nobody had thought of."

Currently, artificially produced dolichol is very expensive, mostly because there hasn't been much demand for it, but the researchers note that the compound is naturally abundant in some plants, such as the gingko or maidenhair tree and spinach. "Ginkgo is already the source of a lot of compounds, so getting dolichol might just mean another step in the extraction process. After that, you could develop a pill that patients could take as a supplement to their diet."

Gleeson and colleagues are now testing their idea with animal models.

While CDG cases are rare, Gleeson and Cantagrel said their discovery about the polyprenol-dolichol block in the glycosylation process has broader ramifications.

Glycosylation is essential to the normal growth and function of all tissues and organs. "If we look at other steps along the glycosylation pathway, it's possible we can find other break points," Gleeson said. "We might be able to treat or cure other forms of CDG or even more common diseases that use this pathway, such as cirrhosis, in which there is deficiency of dolichol."

Source: University of California - San Diego