Protein Misfolding Diseases

Proteins are large, exquisitely folded molecules that play essential and diverse roles in all living organisms. Proteins must achieve and retain a specific 3-dimensional conformation in order to function properly. If protein folding is disrupted, proteins can display sticky surfaces and aggregate through several stages eventually assembling into fibers (shown below), and such nonfunctional protein aggregates can be toxic. Protein misfolding diseases are found in multiple organs, and can be defined histopathologically by the presence of specific misfolded protein(s) deposits.

While misfolded protein diseases often feature complex interactions between aggregates of multiple proteins, all misfolded proteins share a common structural feature, known as the “amyloid fold.”

An effective therapy must solve three major challenges in the treatment of misfolded protein diseases:

  1. Target a broad spectrum of misfolded proteins (e.g. Aβ, tau, α-synuclein, prion) by recognizing a common amyloid protein conformation.
  2. Bind, dissociate and prevent formation of pathological misfolded protein assemblies at key stages (oligomers, fibrils, plaques).
  3. Block cell-to-cell spread of misfolded proteins.

Click here to learn how our GAIM therapy uniquely solves these challenges.