Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Carnitine is a pharmacological allosteric chaperone of the human lysosomal α -glucosidase

Abstract : Pompe disease is an inherited metabolic disorder due to the deficiency of the lysosomal acid α-glucosidase (GAA). The only approved treatment is enzyme replacement therapy with the recombinant enzyme (rhGAA). Further approaches like pharmacological chaperone therapy, based on the stabilising effect induced by small molecules on the target enzyme, could be a promising strategy. However, most known chaperones could be limited by their potential inhibitory effects on patient's enzymes. Here we report on the discovery of novel chaperones for rhGAA, L- and D-carnitine, and the related compound acetyl-D-carnitine. These drugs stabilise the enzyme at pH and temperature without inhibiting the activity and acted synergistically with active-site directed pharmacological chaperones. Remarkably, they enhanced by 4-fold the acid α-glucosidase activity in fibroblasts from three Pompe patients with added rhGAA. This synergistic effect of L-carnitine and rhGAA has the potential to be translated into improved therapeutic efficacy of ERT in Pompe disease.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03400634
Contributor : Gerlind Sulzenbacher Connect in order to contact the contributor
Submitted on : Monday, October 25, 2021 - 10:07:32 AM
Last modification on : Friday, April 1, 2022 - 3:57:05 AM

Links full text

Identifiers

Collections

Citation

Roberta Iacono, Nadia Minopoli, Maria Carmina Ferrara, Antonietta Tarallo, Carla Damiano, et al.. Carnitine is a pharmacological allosteric chaperone of the human lysosomal α -glucosidase. Journal of Enzyme Inhibition and Medicinal Chemistry, Informa Healthcare, 2021, 36 (1), pp.2068-2079. ⟨10.1080/14756366.2021.1975694⟩. ⟨hal-03400634⟩

Share

Metrics

Record views

25