Emerging Field of Proteomics Provides New Insights on Inherited Disease

Farm life is hard on the hands. Dale Hormann's 65 years on the land is testament to that—decades of throwing bales of hay, gripping the steering wheel of a tractor or combine, turning a screw driver, guiding a welding torch. So when he began feeling pain in his hands about 15 years ago, Dale just tried to ignore it.

When the pain spread to his legs, and even when he developed persistent, chronic diarrhea that eventually caused him to lose 56 pounds, Dale stoically continued working his 1,000 acres of soy beans and wheat.

Finally, about three years ago, he sought medical help. That led to hand and back surgery. But neither treatment helped.

"I was losing feeling in my legs and hands, and it hurt so bad," Dale says. "Finally, when nothing was getting better, I went down to Rochester, to Mayo. That turned everything around."

Old-Fashioned Physical Exam: New-Fangled Technology

An innovative combination of the most ancient form of medical science—close, thorough, thoughtful examination of the patient - and the most sophisticated modern technologies, including a new subspecialty of molecular biology called proteomics revealed the true source of Dale's ills.

Dale suffers from a rare disorder of liver proteins called familial amyloidosis.

The diagnosis itself was a relief. "It took 67 tests—I counted," Dale says with a laugh. "It's just good to get the wondering over."

While Dale's wondering may be over, the fact remains that the news is mixed.

Experimental Blood Test Provides Hope for Dale's Children

Familial amyloidosis is an inherited disease. Currently, the only cure for it is a liver transplant. But that procedure is only suitable for younger people.

The good news is that researchers in the Mayo Clinic Proteomics Research Center worked with Dale's physician, Steven Zeldenrust, M.D., Ph.D., a Mayo Clinic researcher and hematologist, to design an experimental blood test. It identified a mutated protein responsible for Dale's nerve and gastrointestinal problems. In just 30 minutes the test could tell Dale's children if they, too, are at risk for the disease that has disabled their father.

The Right Stuff: Experience, Expertise, Exchange, Equipment

"This is the kind of disease that, if you don't know what you're looking for, you won't find it," says Dr. Zeldenrust. "We're fortunate at Mayo because we have incredible depth of experience with the entire family of diseases known as amyloidosis. We can help Mr. Hormann only by treating the symptoms to ease his discomfort. But we can reach the younger generation with a potential cure."

Dr. Zeldenrust credits Mayo's expertise in protein analysis—an expertise that has increased since the opening of the Mayo Proteomics Research Center—with development of the experimental research blood test. Mayo recently installed the world's only 12-Tesla Fourier Transform Ion Cyclontron Resonance Mass Spectrometer for the study of proteins and DNA in medicine.

"The high-precision mass spectrometry analyses necessary for this test give us a level of information we couldn't get before,'' he says. "For the kind of thing we're doing, you can't go just anywhere. The kind of equipment and expertise that the Mayo Proteomics Research Center has available, the sensitivity and the accuracy of the measurements, make the difference - they're 100 times better than what's been available before.''

And you need Mayo's unique exchange between basic scientists and clinicians, according to David Muddiman, Ph.D., Director of the W.M. Keck FT-ICR Mass Spectrometry Laboratory, which is part of the Mayo Proteomics Research Center.

"For a researcher like myself, the opportunity to collaborate directly with a physician like Dr. Zeldenrust and patients like the Hormann family is really a privilege," says Dr. Muddiman. "To see patient care improve as a result of this is a phenomenal feeling. It's what Mayo is all about. We know that familial amyloidosis causes plaques to form throughout the body. At the Mayo Proteomics Research Center, we can examine the protein involved and tell if a genetic variant gave rise to the disease."

Reaching Out for the Benefit of All Patients, Including Those Beyond Mayo's Walls

Mayo is committed to sharing its research developments to decrease the burden of human disease for all people. This spring, the test to detect familial amyloidosis will be used to see if his sons are at risk for the disease - before symptoms develop, and while they are young enough to take action.

Investigators are hopeful that the test can be developed into one that could become widely available for clinical diagnostic use sometime in the next year or two. But first it must meet validation standards and pass Mayo's stringent internal review process.

Dale says the possibility of the new test is deeply satisfying to him. "It would give me a good feeling to know they learned something from all I went through. I signed all the papers at Mayo to do all the experiments. I'll do most anything if it can help the doctors at Mayo come up with something so other people don't have to go through all this," he says.

"Patients like Mr. Hormann are an immense help to research that has the potential to vastly improve clinical practice," says Dr. Zeldenrust. "Our hope is that with continued research and early diagnosis, we'll be able to do more for patients by designing more effective treatments—even cures."