Cellular mechanisms to clear misfolded proteins, and therapies to minimize toxicity by stimulating degradation of misfolded proteins
Research in the Perlmutter lab focuses on misfolded proteins and has led to advances in the general understanding of how cells get rid of misfolded proteins that otherwise would accumulate and become toxic. Based on this research, Perlmutter and his colleagues developed a pipeline of drugs that stimulate degradation of a misfolded protein in alpha-1 antitrypsin deficiency (ATD), and prevent liver damage in a mouse model of ATD. The first of the drugs already has moved into a Phase 2 clinical trial in people with the condition. The goal of the trial is to determine whether this class of drugs can eliminate the future need for liver transplantation. Because these drugs target a critical cellular degradation mechanism that declines with aging, they are being considered for treatment of age-dependent degenerative diseases.