pharmacological Chaperone therapy

Dorphan is developing pharmacological chaperone therapies for the treatment of lysosomal storage diseases. In many cases, genetic mutations in lysosomal enzymes lead to improper folding and destabilization of the proteins which get degraded instead of going into the lysosomes to exercise their enzymatic functions. In the absence of the lysosomal enzyme, cellular debris accumulates, producing progressive damage leading to the disease. Pharmacological chaperones are small molecules designed to specifically bind and rescue mutated enzymes, by improving their stability, transport and activity in the lysosomes.

reticulum endoplasmique


Current treatments such as enzyme replacement therapy, are only available for a small subset of lysosomal storage diseases and have not been effective at treating neurological symptoms, as tissue accessibility and cellular penetration can be limited. The bones and central nervous system are very difficult to access for large protein therapeutics. Substrate reduction therapy is another therapeutic solution already exploited for Gaucher disease, and gene therapy is currently tested for several lysosomal storage diseases with programs at the early stage of development.

The pharmacological chaperone strategy offers many advantages in comparison to the other therapeutic options mentioned above:

  • Oral bioavailability
  • Distribution in the target organs (i.e. brain and bones)
  • No immunogenicity
  • Potential for combination therapies