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Review
. 2021 Nov 29;26(23):7223.
doi: 10.3390/molecules26237223.

Pharmacological Chaperone Therapy for Pompe Disease

Marc Borie-Guichot  1 , My Lan Tran  1 , Yves Génisson  1 , Stéphanie Ballereau  1 , Cécile Dehoux  1
Affiliations
Review

Pharmacological Chaperone Therapy for Pompe Disease

Marc Borie-Guichot et al. Molecules. .

Abstract

Pompe disease (PD), a lysosomal storage disease, is caused by mutations of the GAA gene, inducing deficiency in the acid alpha-glucosidase (GAA). This enzymatic impairment causes glycogen burden in lysosomes and triggers cell malfunctions, especially in cardiac, smooth and skeletal muscle cells and motor neurons. To date, the only approved treatment available for PD is enzyme replacement therapy (ERT) consisting of intravenous administration of rhGAA. The limitations of ERT have motivated the investigation of new therapies. Pharmacological chaperone (PC) therapy aims at restoring enzymatic activity through protein stabilization by ligand binding. PCs are divided into two classes: active site-specific chaperones (ASSCs) and the non-inhibitory PCs. In this review, we summarize the different pharmacological chaperones reported against PD by specifying their PC class and activity. An emphasis is placed on the recent use of these chaperones in combination with ERT.

Keywords: Pompe disease; lysosomal storage disease; pharmacological chaperone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of N-alkyl and C-alkyl derivatives of DNJ: d-DNJ and l-DNJ, N-methyl-DNJ (NM-DNJ), N-butyl-DNJ (NB-DNJ), N-octyl-DNJ (NO-DNJ), N-nonyl-DNJ (NN-DNJ), N-dodecyl-DNJ (ND-DNJ), C-octyl-DNJ (CO-DNJ) and C-nonyl-DNJ (CN-DNJ), N-(7-oxadecyl)-DNJ (NOD-DNJ), N-hydroxyethyl-DNJ (miglitol) and α-1-C-alkyl-d-xylitol (α-1-C-nonyl-DIX).
Figure 2
Figure 2
PC with a pyrrolizidinic or pyrrolidinic structures.
Figure 3
Figure 3
Carbohydrates evaluated as GAA PC.
Figure 4
Figure 4
Ambroxol and its derivatives.
Figure 5
Figure 5
Aminoacids acting as non-inhibitory PCs.
Figure 6
Figure 6
ML201 and its derivative CID36649951.
Figure 7
Figure 7
Structures of CID1512045 and ML247.
See this image and copyright information in PMC

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