Sufferers of the disease porphyria cutanea tarda (PCT), which among other things makes a person “allergic” to sunlight, gained new allies against the disease in the form of University of Utah-bred mutant mice.
The mice provide a working model of the disease for participating molecular biologist John Phillips, pharmacologist Michael Franklin, hematologist James Kushner and several other U faculty members.
The article chronicling their research, “A mouse model of familial porphyria cutanea tarda,” appeared in the Jan. 2 issue of Proceedings of the National Academy of Sciences.
PCT happens because of a deficiency in the blood which causes fragile skin, liver damage and a severe allergic reactions to sunlight. Non-visible portions of sunlight penetrate the skin, affect the diseased blood and cause skin lesions.
“In some individuals these lesions can be so severe it will deteriorate all the skin, and you can see the tendons that move the fingers,” Phillips said. Staying out of the sunlight is the best way to prevent the lesions.
To protect itself, though, the body will grow more hair and thicken the skin. Because of this mechanism, PCT has been often labelled a “werewolf” disease.
“We try to dispel those thoughts,” Phillips said. “If your mother had this disease, you wouldn’t want people thinking of [her] as a werewolf.”
According to the Porphyria Educational Services Web site, the PCT symptoms are typically observed in a person’s 30s or 40s. Approximately one in 5,000 people have the disease.
The disease can be triggered only in a person with a genetic disposition to PCT by “multiple factors,” Franklin said, such as a drug, a chemical agent or even over-the-counter pills.
The exact factors are unknown. Suspected risk factors include alcohol abuse, excesses of estrogen (such as after menopause or resultant from birth control pills), hepatitis C, and external environmental factors, such as diet or pesticides, Franklin said.
A mutant gene, HFE, is also a risk factor in triggering PCT. HFE causes hemochromatosis, where iron in the bloodstream “overloads,” or builds up in the liver, heart, pancreas, hormone system and joints. PCT is also characterized by “iron overload.”
Discovering all factors is the researchers’ ultimate hope. “But you can’t go exposing people to a lot of chemicals to find out what it is; that’s why you need an experimental model,” Franklin said.
To develop such a model, the researchers cross-bred two groups of mice, one genetically-inclined to develop PCT and the other to iron-overloaded blood. The combination of these two genetic inclinations provides ideal subject matter for the research.
“That was sort of the fancy, little trick that we did,” Phillips said. “The reason that a mouse model of this disease is so important is that not many people with this disorder are willing to give up their livers.”
The definitive way to test for PCT is perform a biopsy on a piece of a person’s liver.
With an animal model, the scientists can identify the molecular pathways that eventually lead to PCT and better determine what causes it.
“If we understand what triggers the disease, we can quickly remove it from [a person’s] diet,” Franklin said. People genetically inclined to PCT could eliminate the foods, substances or drugs that catalyze the disease and prevent its symptoms.
If simple lifestyle changes could prevent PCT, it would be a drastic improvement over current treatment, which resemble crude practices of the Dark Ages.
To help patients cope with the “iron overload,” medical professionals regularly “let blood.” Initially 10 to 20 units of blood are drawn every week, then every couple of weeks, then once a month, Phillips said.
Urine testing can also indicate that someone has contracted PCT. By shining black light on a patient’s sample of urine, Phillips can usually tell that he or she has the disease if it turns “pumpkin orange.”
Readily available genealogical information improves investigation of PCT and other genetic diseases in Utah.
“That’s going to really help in solving a lot of the disease problems that come up,” Franklin said. “It’s going to be a while before we have the answer, but hopefully we’re getting closer.”
The research is indicative of “the collaborative stuff that works well here on campus between…seemingly disparate departments,” Franklin said of the researchers exploring the disease.
