Into the Fold [Medicine at Michigan]

Scott Matzka first noticed something was wrong when his finger locked up while applying drywall at home in Kalamazoo. 

The retired University of Michigan and pro hockey player soon developed other troubles: a hand that refused to unclench, a forearm that cramped suddenly. Eventually Matzka was diagnosed, at 36, with limb-onset amyotrophic lateral sclerosis, or ALS — also known as Lou Gehrig’s disease. ALS is a neurodegenerative disease that can manifest in many ways, but which bodes a short lifespan. 

“There is really nothing that you do after [diagnosis] except try to go live your life,” Matzka says. 

But a door onto the ALS mystery is opening, raising hopes for a future with effective therapies for patients like Matzka. New research shows that seemingly unrelated conditions like ALS, heart disease, diabetes and aging have something in common: misfolded proteins in the cell. 

Proteins are long strings of amino acids that must twist, double up and fold in on themselves, morphing into just the right shape to assume their proper place in the cell’s machinery. The cell has several complex “quality-control” processes to help ensure this goes smoothly and that faulty proteins are repaired or removed. Many diseases in different organ systems have been found to occur in part because protein folding has gone wrong. 

U-M researchers are now studying those folding flaws in a cross-disciplinary research effort called the Protein Folding Diseases Initiative, or PFDI. Some 70 researchers from around the university are exploring the basic mechanisms and consequences of misfolded proteins in human diseases like ALS. This approach holds promise because it may lead to new drugs, or repurpose existing ones, in order to help patients who might be running out of options...READ MORE