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Review
. 2022 May 13:13:863667.
doi: 10.3389/fphar.2022.863667. eCollection 2022.

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy

Anna-Maria Wiesinger  1   2 , Brian Bigger  2   3 , Roberto Giugliani  4 , Maurizio Scarpa  2   5 , Tobias Moser  6 , Christina Lampe  2   7 , Christoph Kampmann  8 , Florian B Lagler  1   2
Affiliations
Review

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy

Anna-Maria Wiesinger et al. Front Pharmacol. .

Abstract

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storage-induced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT).

Keywords: MPS; cytopathology; drug discovery; immunomodulation; inflammation; mucopolysaccharidoses.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Inflammatory pathway cue to GAG storage in MPS (orange arrows indicate the process mainly due to HS accumulation, blue arrows indicate processes due to HS, DS, C4S, C6S, KS, and HA accumulation).
FIGURE 2
FIGURE 2
Direct immunomodulatory molecules, which target the cytokine receptor pathway and have already been tested in MPS trials.
FIGURE 3
FIGURE 3
Target points of Abatacept, Alemtuzumab, Anakinra, Adalimumab, and Infliximad. Adaliminab and infliximab block the action of INF-a, Anakinra inhibits the ILI receptor and a following ILI release, Alemtuzumab targets mature B- and T-cells via CD52, Abatacept prevents full T-cell activation via CD80 and CD86 between antigen presenting cell (APC) and T-cell.
See this image and copyright information in PMC

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