L-, D-, and acetyl-D-carnitine are novel chaperones for the recombinant acid α-glucosidase (rhGAA) enzyme, a new study published in the Journal of Enzyme Inhibition and Medicinal Chemistry found. This could mean that the efficacy of enzyme replacement therapy (ERT) with rhGAA to treat Pompe disease could be enhanced using these newly identified chaperones.

ERT with recombinant enzymes is the standard of care for Pompe disease and the only approved treatment for the disease. However, this approach is not effective in all patients. Factors affecting the efficacy include the age of the patient at the start of treatment, their immunological status, insufficient targeting of the enzyme to muscles, and the possible instability of the recombinant enzyme.

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Chaperone therapy is an alternative treatment modality being explored for Pompe disease. It uses small-molecule ligands that can bind directly to the defective enzyme to template its folding in the most stable conformation.

In the present study, a team of researchers from Italy and France led by Marco Moracci, professor of biochemistry at the University of Naples Federico II in Italy, reported the discovery of 3 novel chaperones that were able to stabilize the acid α-glucosidase (GAA) enzyme without inhibiting its activity.

The researchers showed that the chaperones were able to enhance the activity of the GAA enzyme 4-fold in the fibroblasts of 3 patients with Pompe disease who were treated with ERT with added rhGAA.

“These molecules are novel potential pharmacological chaperones with excellent perspectives for the treatment of Pompe disease alone and in combination with ERT,” the researchers concluded. 

L-carnitine and D-carnitine, as well as the related compound acetyl-D-carnitine, are already approved as nutraceuticals or drugs and could be rapidly translated for human therapy without the need for phase 1 clinical trials.


Iacono R, Minopoli N, Ferrara MC, et al. Carnitine is a pharmacological allosteric chaperone of the human lysosomal α-glucosidase. J Enzyme Inhib Med Chem. Published online September 27, 2021. doi:10.1080/14756366.2021.1975694