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Prom and Pumping Iron Makes Biochemical Research Look Like High School

Managing iron in the body is a lot like chaperoning a high school dance, according to Dr. Richard Watt.

“If you think of a dance, you have chaperones there to prevent dangerous reactions from taking place,” Watt said. “The metallochaperone proteins are in our body to bind metals . . . but if iron is not properly handled, it causes all of these side reactions that make dangerous chemicals.”

Watt researches how the body regulates the small amounts of iron needed to catalyze chemical reactions on the cellular level.

“The goal of our research is to understand how iron is moved around in a healthy person and then look at people that have these different diseases and evaluate where the iron is accumulating, what kind of damage it is causing, and then try to figure out which one of the metallochaperones stopped functioning and why,” Watt said.

Metallochaperones are constantly pumping iron in or out of a cell. When these minute levels of iron get out of balance, the body experiences an adverse response. For example, abnormally high iron levels have been linked to Alzheimer’s and Parkinson’s disease, while low levels have been associated with anemia and other sicknesses.

Watt is researching two projects that address both sides of iron dysregulation.

“High iron, low iron—we do it all,” Watt said.

One project Watt’s team is tackling challenges the normal hypothesis for the cause of Alzheimer’s. The disease is known to produce protein buildups called amyloid plaques and tau tangles, and a common theory is that these accumulations cause the cerebral malfunction demonstrated in Alzheimer’s-afflicted patients. Dr. Watt, however, hypothesizes that the plaques and tangles are secondary and are produced to protect the brain against the abnormal amounts of iron seen in Alzheimer’s patients.

“We think that maybe iron is getting too high in the cell and that cells are trying to get the iron out,” Watt said. “To protect themselves from the iron, the [cells] are packaging the iron in the amyloid plaques and tau tangles. That’s a hypothesis with Alzheimer’s.”

Watt’s work adds to a global body of research arguing that these proteins are a by-product of the high iron levels caused by certain diseases. Similar metal accumulation in protein plaques have been found in the brains of patients with Parkinson’s disease.

“The original hypothesis was that these plaques were killing the brain,” Watt said “A new model suggests that the plaques might be made to protect the brain from the dangerous effects of iron. It’s a shift in thinking, trying to determine what is causative agent for Alzheimer’s disease.”

A separate, concurrent project of Watt’s is the development of hepcidin inhibitors. Hepcidin is the hormone that controls how iron is redistributed in the body, and it is produced in high amounts when the body is inflamed. This can prevent the absorption of iron.

“We’re trying to trick the body into shutting down hepcidin production,” Watt said. “That would then let the body absorb the iron, send the iron to the bone marrow, and then restore red blood cell levels to carry enough oxygen.”

Developing a treatment for inflammation-induced anemia is “a really hot topic in the bio-iron field,” according to Watt.

“If we could either pretreat patients before surgery to get their blood levels as high as possible or treat them right after surgery to help them maintain a healthy blood supply, that would help them heal more quickly,” Watt said.

The hepcidin inhibitor research is progressing well. The culmination of this research would be to develop a commercially available drug to manage hepcidin levels, and Watt is getting close to that goal.

“We’re at the point where we’re trying to team up with a pharmaceutical company right now,” Watt said.

By Mitch Rogers Posted on