Researchers Make Breakthrough in Fighting Rare Metabolic Disease

A new medical breakthrough shows promise for the treatment of a rare and deadly metabolic disorder known as Mucopolysaccharidosis I (MPS I).

Though the disorder is rare, only affecting every one of 100,000 people, MPS I is a documented killer. Children born with a severe form of the disease usually die before they are 10 years old. However, those with less severe forms of MPS I can live well into adulthood. According to researchers from the University of Alberta Faculty of Medicine and Dentistry, characteristics of the disease include "improperly formed bones and teeth, carpal tunnel syndrome, an enlarged spleen, hearing or vision problems, distinct facial characteristics, heart problems and mental delays."

The University of Alberta researchers have discovered the structure of a potential drug target for the rare genetic disease. They've published their findings in the journal Nature Chemical Biology.

Malfunctioning enzymes cause MPS I to affect the body in a number of ways, for example, by inhibiting the process of rebuilding bone and cartilage. The way a normal body metabolizes, the bones in the body are replaced every seven years though a gradual rebuilding process.

"Your body has to have a way of doing this, so that there is a breakdown of bone and then a production of the bone building-blocks," said research associate and team member Jiang Yin. For people with MPS I, the body cannot complete this process due to a malfunctioning enzyme, Yin said. A genetic mutation in the enzyme prevents this natural rebuilding process from taking place.

Researchers have been trying to better understand the enzyme and how it become malformed. The latest progress in that quest was made by the Alberta researchers, who have determined the three-dimensional structures of the enzyme and the specific defects in it that cause symptoms of MPS I.

"Now that we know how this enzyme functions and where the mutations are, the sites of the mutations can now be related to the disease symptoms" said researcher Michael James. "We've identified a drug target. There won't be a cure yet, but hopefully we can develop drugs to treat the less severe forms of the disease."

Yin added: "If we can treat people in the early stages of the disease, we may be able to lessen the severity of the disease and the mental delays."

Click here to read more about MPS 1.

In the photo below, a child with hepatosplenomegaly, which is an enlargement of both the liver and spleen.