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Home >> Science & Technology >> Overview
Pharmacological Chaperone Technology:
Single Platform, Dual Approach
Amicus is leveraging its pharmacological chaperone technology to develop next-generation treatments for human genetic diseases by targeting mutated proteins that are unstable, unfolded or misfolded. Pharmacological chaperones are orally available small molecules designed to selectively bind to a target protein, increase its stability and help keep it folded in the correct three-dimensional shape.
In lysosomal storage diseases (LSDs), such as Fabry disease, Pompe disease, and Gaucher disease, a mutation in a patient’s own (endogenous) enzyme may lead to a decrease in protein stability, and even misfolding or unfolding of the enzyme. For patients with LSDs who are receiving enzyme replacement therapy (ERT), the infused (exogenous) protein may unfold and lose activity at any stage in the process - from the infusion bag to the bloodstream, to the eventual uptake into cells and tissue. This instability and unfolding of endogenous or exogenous enzyme causes it to lose activity and may disrupt proper trafficking of the enzyme to lysosomes where it is needed to degrade the lipid substrate.
For LSDs, pharmacological chaperones are designed to bind to, and facilitate trafficking of, both endogenous and exogenous enzymes to the location in cells where they are needed. This important feature has allowed Amicus to develop pharmacological chaperones as monotherapy agents (to be used without ERT); and in combination with ERT for the treatment of LSDs.
Proposed mechanism of action for LSDs:
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As monotherapy agents, pharmacological chaperones are designed to bind to the endogenous target enzyme, stabilizing the enzyme in its properly folded active form and facilitating cellular trafficking to lysosomes. This allows for increased activity, improved cellular function and potentially reduced cell stress.
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In combination with ERT, pharmacological chaperones are designed to bind to infused exogenous enzyme, stabilizing the enzyme in its properly folded and active form. This allows for enhanced tissue uptake, greater lysosomal activity and more reduction of substrate.
For more information on the proposed mechanism of action, please click here.
Fore more information on protein instability, unfolding, misfolding and disease, please click here.
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What's Missing in Lysosomal Storage Diseases?
(pdf - 1.6MB)
About Pharmacological Chaperones
(pdf - 640KB)
Glossary
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