Funding from this award will support Simpson Lab personnel and provide supplies for research aimed at investigating how mutations in the gene encoding the calcium pump SPCA1 cause Hailey-Hailey Disease (HHD) using human cellular and tissue models. 

The Simpson Lab at the University of Washington has been awarded a three-year $590K grant by the LEO Foundation for ongoing research in Hailey-Hailey disease (HHD).

Funding from this award will support Simpson Lab personnel and provide supplies for research aimed at investigating how mutations in the gene encoding the calcium pump SPCA1 cause Hailey-Hailey Disease (HHD) using human cellular and tissue models. 

Several rare blistering disorders are linked to autoantibodies or gene mutations that disrupt desmosomes, causing keratinocyte splitting and skin breakdown. While autoimmune blistering diseases can be controlled by suppressing the immune system, treatments remain elusive for inherited blistering diseases such as HHD, which causes recurrent wounds, pain, and infections, leading to stigmatization of patients. 

Mutations in the ATP2C1 gene, which encodes the calcium pump SPCA1, were linked to HHD more than 20 years ago, yet the disease still lacks any approved therapies. 

While it is known that SPCA1 resides in the Golgi apparatus, there’s limited understanding of how SPCA1 deficiency compromises skin integrity which has stalled drug development for HHD; moreover, mice engineered to lack SPCA1 did not replicate HHD. 

Cory Simpson, MD, PhD, and his team have built human cellular and tissue models of HHD to define what drives the disease and to discover new treatments. Their preliminary analysis of ATP2C1 mutant keratinocytes revealed impaired expression and trafficking of adhesive proteins, but also identified stress signals from mis-folded proteins and reactive oxygen species. 

In the new project, “Modeling Hailey-Hailey disease to delineate its pathogenesis and identify therapeutic strategies,”  Dr. Simpson and team will determine how these cellular dysfunctions compromise keratinocyte cohesion to cause skin blistering and test if cell stress pathways could serve as therapeutic targets for HHD.