Platform Technologies | Amicus Therapeutics

Platform Technologies

Our technologies are intended to stabilize proteins with either a pharmacological chaperone on its own or a novel Enzyme Replacement Therapy in combination with a chaperone.

Protein Misfolding in Lysosomal Storage Disorders (LSDs)

Lysosomal Storage Disorders (LSDs) result from genetic variants or mutations in specific lysosomal enzymes, proteins that function in the lysosomal compartment to degrade molecules (substrates) into smaller pieces that can be used to build new molecules. Genetic variants or mutations in a patient’s own (endogenous) lysosomal enzyme may lead to a complete absence of the enzyme or a decrease in the protein’s stability, and even misfolding or unfolding of the enzyme. Unstable, unfolded, or misfolded lysosomal enzymes are generally not efficiently transported to their intended destination in the cell (ie., the lysosome) to degrade substrate. This complete or partial loss of protein function and enzymatic activity may lead to several problems, including:

  • Substrate accumulation;
  • Disruption of cellular function; and
  • Cell death.

We have developed a pharmacological chaperone technology designed to treat LSDs that are characterized by mutated proteins that are unstable, unfolded, or misfolded. Pharmacological chaperones are small molecules designed to selectively bind to a target enzyme to potentially increase its stability and help keep it folded in the correct three-dimensional shape. For LSDs, pharmacological chaperones are designed to bind to, and facilitate trafficking of, both endogenous and exogenous amenable enzymes to the location in cells where they are needed, i.e., the lysosomes.

Lysosomal Storage Disorders result from genetic variants or mutations in specific lysosomal enzymes, proteins that function in the lysosomal compartment to degrade molecules (substrates) into smaller pieces that can be used to build new molecules. Variants in a patient’s own (endogenous) lysosomal enzyme may lead to a decrease in the protein’s stability, and even misfolding or unfolding of the enzyme. Unstable, unfolded, or misfolded lysosomal enzymes are generally not efficiently transported to their intended destination in the cell (ie., the lysosome) to degrade substrate. This complete or partial loss of protein function and enzymatic activity may lead to several problems, including:

  • Substrate accumulation;
  • Disruption of cellular function; and
  • Cell death.

We are leveraging our proprietary Chaperone-Advanced Replacement Therapy (CHART®) technology to develop chaperone/ERT combinations that may benefit patients with LSDs. In each CHART® program, a pharmacological chaperone is designed to bind to a specific therapeutic (exogenous) enzyme, and to stabilize the enzyme in its properly folded and active form.