FoldRx is a leader in the discovery and development of first in class disease modifying drug therapies for diseases of protein misfolding and amyloidosis.

Description of Protein Folding and Misfolding:

The folding and maintenance of proteins in a correctly folded active form is essential to normal cellular function. The folding of proteins, both as individual units, and as parts of larger complexes, is determined by many factors including the protein primary amino acid sequence and the environment in which it folds. Proteins must be synthesized, assembled and then translocated to the appropriate intracellular or extracellular compartment folded correctly to permit optimal function. Correct folding of proteins during synthesis and trafficking is maintained by a dual quality control system. One component is an energy dependant chaperone system that holds the protein correct conformation as it moves from one intracellular compartment to another. The second is protein degradation (ubiquitin/proteosome) system that identifies and degrades improperly folded and damaged proteins.

View schematic of protein folding/misfolding

Factors that tilt the balance between correctly folded proteins and misfolded proteins are common causes of disease. The balance can be perturbed as the result of an age-related reduction in the efficiency of the quality control system and/or the acquisition, or inheritance, of mutations in the primary sequence of the protein. Both lead to incorrect folding, lost activity, improper trafficking, and/or misfolding outside the confines of the endoplasmic reticulum and cytoplasm. The net result of such events is that the quality control system becomes overwhelmed and unable to degrade all the misfolded proteins, leading to the accumulation of proteins with insufficient activity to perform their function or to the accumulation of toxic misfolded intermediates that themselves lead to pathology.

The role of protein misfolding in the pathogenesis of human disease is an emerging and exciting field of research. Several previously unrelated diseases, such as prion diseases, diabetes, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, familial amyloidosis and cancer share a common feature of aggregation and deposition of misfolded protein. Several disorders, such as cystic fibrosis, lyzosomal storage diseases, nephrogenic diabetes insipidus and cancer result from a common cell’s trafficking machinery defect due to protein misfolding.

FoldRx Pharmaceuticals intends to exploit its scientific platform to develop drug for the treatment of diseases of protein misfolding.



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