In the small northern Swedish town of Skellefteå, a mysterious illness has puzzled doctors and patients for generations. Now, researchers at Umeå University believe they have uncovered an important piece of the puzzle.
Hereditary TTR amyloidosis — locally called "Skellefteå disease" — is caused by a genetic mistake called the TTR-Val30Met mutation. The illness happens when a protein in the body misfolds, or folds incorrectly, and builds up in tissues like the nerves, heart, and digestive system. But here's the mystery: not everyone with the genetic mutation gets sick. Some people develop symptoms early in life, others much later, and some never get ill at all.
"Our results support a model in which the genetic TTR variant is not the only factor that determines whether and when the disease develops," said Anders Olofsson, an associate professor at Umeå University's Department of Clinical Microbiology who led the research. "The body's ability to maintain a functional redox balance may also be important."
The research team found that patients with the disease have disrupted antioxidant systems. Specifically, they found high levels of pyroglutamate (PGA) — a marker that shows problems with glutathione metabolism, one of the body's main defenses against harmful molecules called oxidative stress. They also found increased activity of an enzyme called IDO1, which is linked to inflammation.
The findings, published in the journal Biomarker Research, led to something potentially very useful: a new test that can identify people at higher risk of developing the disease. The test combines PGA and IDO1 markers and can predict disease risk with about 80 percent accuracy in women and close to 90 percent in men.
"These biomarkers could become a valuable complement to the clinical monitoring of individuals with hereditary ATTR amyloidosis," said Anushree Bachhar, a postdoctoral researcher at Umeå who was the study's first author.
This matters because catching the disease early — before permanent tissue damage occurs — could make a real difference for patients. The researchers say their work also raises the possibility of developing new treatments that boost the body's antioxidant defenses, though they caution that clinical trials would still be needed to test whether such treatments actually work.
Work to launch those trials is already underway, and the team considers it a high priority. For patients and families in northern Sweden who have watched this disease pass through generations, these findings offer new hope that better detection and new therapies may be on the horizon.