Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges

Thomas A. Nicholson; Michael Sagmeister; Susanne N. Wijesinghe; Hussein Farah; Rowan S. Hardy; Simon W. Jones

doi:10.3390/pharmaceutics15010237

Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges

Thomas A. Nicholson, Michael Sagmeister, Susanne N. Wijesinghe, Hussein Farah, Rowan S. Hardy, Simon W. Jones^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Original language	English
Article number	237
Number of pages	19
Journal	Pharmaceutics
Volume	15
Issue number	1
DOIs	https://doi.org/10.3390/pharmaceutics15010237
Publication status	Published - 10 Jan 2023

Bibliographical note

Funding Information:
This research was funded by the Medical Research Council, grant number MR/W026961/1 and Versus Arthritis, grant number 21530.

Publisher Copyright:
© 2023 by the authors.

Keywords

bone
cartilage
oligonucleotides
osteoarthritis
osteoporosis
rheumatoid arthritis
sarcopenia
skeletal muscle
synovium
Review

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.3390/pharmaceutics15010237Licence: Creative Commons: Attribution (CC BY)

NicholsonT2023OligonucleotideFinal published version, 1.68 MBLicence: Creative Commons: Attribution (CC BY)

1 Finished
1 Active

MICA: Synovial fibroblast pain pathotypes: A roadmap to understanding and targeting the complexity of patient-reported joint pain in osteoarthritis
Jones, S. & Gkoutos, G.
Medical Research Council
1/05/22 → 30/04/25
Project: Research Councils
Are synovitis-associated IncRNAs central regulators of inflammatory pain in patients with knee OA: A route to identifying a novel analgesic drug for OA patients
Hardy, R. & Jones, S.
ARTHRITIS RESEARCH UK
1/11/17 → 31/07/23
Project: Research

Cite this

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title = "Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges",

abstract = "Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.",

keywords = "bone, cartilage, oligonucleotides, osteoarthritis, osteoporosis, rheumatoid arthritis, sarcopenia, skeletal muscle, synovium, Review",

author = "Nicholson, {Thomas A.} and Michael Sagmeister and Wijesinghe, {Susanne N.} and Hussein Farah and Hardy, {Rowan S.} and Jones, {Simon W.}",

note = "Funding Information: This research was funded by the Medical Research Council, grant number MR/W026961/1 and Versus Arthritis, grant number 21530. Publisher Copyright: {\textcopyright} 2023 by the authors.",

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language = "English",

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T2 - Successes and Challenges

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AU - Sagmeister, Michael

AU - Wijesinghe, Susanne N.

AU - Farah, Hussein

AU - Hardy, Rowan S.

AU - Jones, Simon W.

PY - 2023/1/10

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Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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Projects

MICA: Synovial fibroblast pain pathotypes: A roadmap to understanding and targeting the complexity of patient-reported joint pain in osteoarthritis

Are synovitis-associated IncRNAs central regulators of inflammatory pain in patients with knee OA: A route to identifying a novel analgesic drug for OA patients

Cite this