Researcher

A.J. (Atze) Bergsma, PhD

Senior researcher, assistant professor

Department
Pediatrics / Clinical Genetics
Focus area
Antisense oligonucleotides, Skeletal muscle, Pompe disease, Pre-mRNA splicing

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A.J. (Atze) Bergsma, PhD

About A.J. (Atze) Bergsma, PhD

Introduction

Dr. Atze Bergsma leads innovative research in antisense oligonucleotide (ASO) therapies for metabolic diseases. Previously, he developed ASOs correcting GAA pre-mRNA splicing defects in Pompe disease. His current work centers on developing platform technology to enhance ASO delivery to skeletal muscle and other tissues, addressing delivery barriers in multi-organ metabolic diseases. His goal is to create scalable, safe delivery systems to increase therapeutic availability for rare disorders. He is a founding member of the Dutch Antisense Therapeutics Society to promote collaboration in this field, highlighting his vision of expanding antisense therapies to ultimately broadening precision medicine’s impact for rare diseases.

Field(s) of expertise

Antisense Oligonucleotide Therapy: Designing ASOs to correct aberrant RNA splicing in metabolic diseases, particularly PD, with demonstrated success in restoring GAA function (Bergsma et al., Mol Ther Nucleic Acids, 2016).
Lipid Nanoparticle Delivery: Developing LNP platforms to enhance ASO delivery to hard-to-reach tissues like skeletal muscle, optimizing formulation and targeting (grant proposal, 2025).
Skeletal Muscle Targeting: Utilizing 2D and 3D iPSC-derived muscle models (3D-TESMs) to study disease mechanisms and test therapeutic efficacy (Herrero-Hernandez et al., Methods Mol Biol, 2020).
Pre-mRNA Splicing Analysis: Expertise in analyzing splicing defects and validating ASO-mediated corrections, critical for metabolic myopathy therapies (Bergsma et al., Euro J Hum Gen, 2021).

Education and career

Dr. Bergsma studied Cellular and Molecular Life Sciences at the Utrecht University, which he graduated from in 2012, after which he started his PhD at the Erasmus MC in the group of Pim Pijnappel, where he focused on development of an antisense based therapy for Pompe Disease. He obtained his PhD in 2016, with his thesis titled: ‘Pre-mRNA splicing in Pompe disease: Prospect for antisense therapy’.

Publications

Generation of Human iPSC-Derived Myotubes to Investigate RNA-Based Therapies In Vitro. Herrero-Hernandez P, Bergsma AJ, Pijnappel WWMP. Methods Mol Biol. 2022;2434:235-243. doi: 10.1007/978-1-0716-2010-6_15. PMID: 35213021

Broad variation in phenotypes for common GAA genotypes in Pompe disease. Niño MY, et al.Hum Mutat. 2021 Nov;42(11):1461-1472. doi: 10.1002/humu.24272. PMID: 34405923

Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease-associated variants, common sequence variants, and results from newborn screening. de Faria DOS, et al. Hum Mutat. 2021 Feb;42(2):119-134. doi: 10.1002/humu.24148. PMID: 33560568

A Generic Assay to Detect Aberrant ARSB Splicing and mRNA Degradation for the Molecular Diagnosis of MPS VI. Broeders M, et al. Mol Ther Methods Clin Dev. 2020 Sep 16;19:174-185. doi: 10.1016/j.omtm.2020.09.004. PMID: 33209960

A generic assay for the identification of splicing variants that induce nonsense-mediated decay in Pompe disease. Bergsma AJ, et al. Eur J Hum Genet. 2021 Mar;29(3):422-433. doi: 10.1038/s41431-020-00751-3. PMID: 33168984

Enzymatic diagnosis of Pompe disease: lessons from 28 years of experience. Niño MY, et al. Eur J Hum Genet. 2021 Mar;29(3):434-446. doi: 10.1038/s41431-020-00752-2. PMID: 33162552

Opportunities and challenges for antisense oligonucleotide therapies. Kuijper EC, et al. J Inherit

Metab Dis. 2021 Jan;44(1):72-87. doi: 10.1002/jimd.12251. PMID: 32391605 Review.

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis. In 't Groen SLM, et al. Mol Ther Methods Clin Dev. 2020 Jan 13;17:337-348. doi: 10.1016/j.omtm.2019.12.016. PMID: 32071926

Extension of the Pompe mutation database by linking disease-associated variants to clinical severity. Niño MY, et al. Hum Mutat. 2019 Nov;40(11):1954-1967. doi: 10.1002/humu.23854. PMID: 31254424

A genetic modifier of symptom onset in Pompe disease. Bergsma AJ, et al. EBioMedicine. 2019 May;43:553-561. doi: 10.1016/j.ebiom.2019.03.048. PMID: 30922962

Alternative Splicing in Genetic Diseases: Improved Diagnosis and Novel Treatment Options. Bergsma AJ, et al. Int Rev Cell Mol Biol. 2018;335:85-141. doi: 10.1016/bs.ircmb.2017.07.008. PMID: 29305015

Antisense Oligonucleotides Promote Exon Inclusion and Correct the Common c.-32-13T>G GAA Splicing Variant in Pompe Disease. van der Wal E, et al. Mol Ther Nucleic Acids. 2017 Jun 16;7:90-100. doi: 10.1016/j.omtn.2017.03.001. PMID: 28624228

GAA Deficiency in Pompe Disease Is Alleviated by Exon Inclusion in iPSC-Derived Skeletal Muscle Cells. van der Wal E, et al. Mol Ther Nucleic Acids. 2017 Jun 16;7:101-115. doi: 10.1016/j.omtn.2017.03.002. PMID: 28624186

From Cryptic Toward Canonical Pre-mRNA Splicing in Pompe Disease: a Pipeline for the Development of Antisense Oligonucleotides. Bergsma AJ, et al. Mol Ther Nucleic Acids. 2016 Sep 13;5(9):e361. doi: 10.1038/mtna.2016.75. PMID: 27623443

Characterization and dynamics of pericentromere-associated domains in mice. Wijchers PJ, et al. Genome Res. 2015 Jul;25(7):958-69. doi: 10.1101/gr.186643.114. PMID: 25883320

Identification and characterization of aberrant GAA pre-mRNA splicing in pompe disease using a generic approach. Bergsma AJ, et al. Hum Mutat. 2015 Jan;36(1):57-68. doi: 10.1002/humu.22705. PMID: 25243733

A central role for TFIID in the pluripotent transcription circuitry. Pijnappel WW et al. Nature. 2013 Mar 28;495(7442):516-9. doi: 10.1038/nature11970. PMID: 23503660

Teaching activities

Research master Genomics in society: Core teacher, course coordinator Genomic Engineering (4 EC), couse coordinator Genomics and the city assignment (20 EC)

Other positions

Atze Bergsma is member of the board of the Dutch Antisense Therapeutics Society (DATS), and member of the board of the Nederlandse Associatie voor Community Genetics and public health Genomics (NACGG). He is also part of the management team of the Research Master Genomics in Society

Scholarships, grants, and awards

2018 Wadman van Gennip prize, Erfelijke stofwisselingsziekten Nederland (ESN)