Technology Platform

Harnessing biophysics to target fleeting intermediates in neurodegenerative disease

We have invested deeply in research studying the behavior of misbehaving protein pathways—both ordered and disordered behavior—to quantify the rules by which these pathways are regulated. Over two decades of work, we have discovered that the assembly of amyloid plaques is a highly predictable biophysical process, tightly regulated by biophysical and biochemical parameters, quantifiable and mappable with network kinetics.

Wren Platform

We are applying these learned rules to design novel medicines to inhibit this neurodegenerative disease process: To block the production of toxic, misbehaving protein forms—specifically, the neurotoxic protein oligomer intermediates produced within this pathway.

The biophysical rules governing amyloid assembly are exquisitely reproducible, allowing us to develop precision assays that express the same dynamic process that occurs in human disease. We are able to replicate the interconnected biochemical network that occurs in the brain, to study a process that previously was hidden from view.

With a deep understanding of the dynamics of protein aggregation assembly, we are mapping the molecular mechanisms that define pathways of protein misfolding and aggregation, first for the major neurodegenerative diseases—from the primary origins in the early stages of disease through the assembly of mature plaques in more advanced disease. We are applying these dynamic rules of amyloid assembly now to Alzheimer's disease, Parkinson’s disease, and ALS, and we will broaden our approach to other diseases beyond neurodegeneration.

  • We have defined the molecular mechanisms and the biophysical rules for the disease process of protein misfolding and aggregation in Alzheimer's disease, Parkinson’s disease, and ALS   
  • We are applying these biophysical rules to develop translational preclinical models to express the same highly conserved amyloid assembly processes that occur in human disease   
  • We are developing biomarkers to measure the on-target effect of our drugs on the progression of the toxic oligomer intermediates in these disease networks in clinical trials

Oligomer formation in Alzheimer's disease