Penn State College of Medicine researchers recently identified a gene variant that is present in an estimated one-third of ALS patients who have an accelerated disease progression. The discovery reportedly could lead to more successful drug trials for all ALS patients.

According to a media release from Penn State, for this study, the researchers crossbred mice with the HFE gene variant with the standard mice used in ALS research.

“When we followed the disease progression and the behavior of our crossbred mice compared to the standard mice, we saw significant differences,” said James Connor, vice chair of neurosurgery research and director of the Center for Aging and Neurodegenerative Diseases. The crossbred mice performed significantly worse on tests of forelimb and hindlimb grip strength and had a 4% shorter life span. The researchers published their findings in BBA Molecular Basis of Disease.

“The disease progression was much faster in the crossbred mice than in the standard mice,” Connor said. “What we found is that when ALS happens in the presence of the HFE gene variant, things go downhill more quickly.”

The lead investigator on this project, graduate student Wint Nandar, noticed that the HFE gene variant sped up disease progression and death in females but not males. Males with ALS die faster, on average, than females.

Connor said the variant may not have had time to accelerate the pace of the disease in male mice. An accelerated progression may show up in clinical trials in human males, who live longer with the disease than mice.

The findings could help direct more successful clinical testing of new drug treatments, which have traditionally had disappointing results. Because patients with H63D HFE have an accelerated form of the disease, their results could skew study findings.

[Source: Penn State College of Medicine]