The Exploitation of the Glycosylation Pattern in Asthma: How We Alter Ancestral Pathways to Develop New Treatments

Author:

Muchowicz Angelika1,Bartoszewicz Agnieszka1,Zaslona Zbigniew1

Affiliation:

1. Molecure S.A., Zwirki i Wigury 101, 02-089 Warszawa, Poland

Abstract

Asthma has reached epidemic levels, yet progress in developing specific therapies is slow. One of the main reasons for this is the fact that asthma is an umbrella term for various distinct subsets. Due to its high heterogeneity, it is difficult to establish biomarkers for each subset of asthma and to propose endotype-specific treatments. This review focuses on protein glycosylation as a process activated in asthma and ways to utilize it to develop novel biomarkers and treatments. We discuss known and relevant glycoproteins whose functions control disease development. The key role of glycoproteins in processes integral to asthma, such as inflammation, tissue remodeling, and repair, justifies our interest and research in the field of glycobiology. Altering the glycosylation states of proteins contributing to asthma can change the pathological processes that we previously failed to inhibit. Special emphasis is placed on chitotriosidase 1 (CHIT1), an enzyme capable of modifying LacNAc- and LacdiNAc-containing glycans. The expression and activity of CHIT1 are induced in human diseased lungs, and its pathological role has been demonstrated by both genetic and pharmacological approaches. We propose that studying the glycosylation pattern and enzymes involved in glycosylation in asthma can help in patient stratification and in developing personalized treatment.

Funder

Preclinical research and clinical trials of a first-in-class development candidate in the therapy of asthma and inflammatory bowel disease

Development of a ‘first-in-class’ small molecule drug candidate for treatment of idiopathic pulmonary fibrosis through chitotriosidase inhibition

Preclinical and clinical development of drug candidate OATD-01, for the treatment of sarcoidosis patients

Publisher

MDPI AG

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