In 2022, an interdisciplinary team of researchers from Amsterdam UMC was awarded the AI&I collaboration grant. The team, comprising Dr. Maarten Steinz, Prof. Dr. Conny van der Laken, Assoc. Prof. Dr. Jan van den Bossche, Dr. Anneke van der Kooi, and Dr. Joost Raaphorst from the departments of Rheumatology & Clinical Immunology, Molecular Cell Biology and Immunology, and Neurology, was recognized for their interdisciplinary approach to understanding muscle dysfunction in patients with rheumatic musculoskeletal diseases (RMDs), in particular rheumatoid arthritis.
Focus of the research project
The research aimed to understand how certain molecules that cause inflammation (called pro-inflammatory cytokines) might be linked to problems in the tiny powerhouses within muscle cells (called mitochondria) in people with RMDs. To do this, the researchers used muscle cells grown in the lab and also looked at muscle samples taken from patients. One of the key findings was that in muscle cells exposed to these inflammatory molecules, the mitochondria did not work as well. This means the cells had trouble producing energy efficiently. In muscle samples from patients with an RMD we found noticeable changes of certain genes. These changes could be related to the mitochondrial dysfunction and inflammation observed. The results of these studies are preliminary and are used for follow-up studies and career-supporting grant applications.
Impact of winning the grant
Dr. Steinz: 'Winning the AI&I collaboration grant was a significant milestone for me. It facilitated in-depth research into the clinically relevant topic of skeletal muscle weakness and fatigue in RMDs, yielding new insights into the underlying causes of these conditions. This accomplishment also meant I could use the findings to secure additional funding, including the AUF startstipendium I have been awarded earlier this year, to continue this important work.'
The team did secure the AUF startstipendium by using the novel findings gathered by the AI&I collaboration grant. Additionally, an application was made to the FOREUM career research grant, emphasizing the preliminary data and the future potential of the research in identifying therapeutic targets. This summer, Dr. Steinz was rightfully awarded this research grant worth 200.000 euros.
Moreover, the AI&I collaboration grant catalyzed the establishment of a new international study group called “EULAR RMD Skeletal Muscle Research.” This consortium aims to enhance knowledge, diagnosis, and therapies for RMD patients suffering from muscle weakness and fatigue. The FOREUM application already involved patient research partners from the EULAR RMD Skeletal Muscle Research group, to ensure a patient-relevant approach.
dysfunction in RMDs, with promising implications for broader medical research and therapeutic development.'
Aspirations and future directions
The primary objectives of the ongoing research, funded by the AUF startstipendium and the FOREUM career research grant, are to delve deeper into mitochondrial dysfunction in RMDs, develop therapeutic interventions, and explore the relevance of these findings in other rheumatic diseases such as osteo-arthritis and in elderly (i.e. with loss of muscle mass, called sarcopenia). The team has already made significant progress, completing initial experiments, data collection, and preliminary data analysis.
Looking ahead, the researchers aspire to deepen their understanding of RMD-associated muscle weakness and fatigue, develop potential therapies, and broaden their research scope through new collaborations. Regular meetings of the EULAR RMD Skeletal Muscle Research Study Group facilitate these collaborative efforts. The team also hopes to involve pharmaceutical partners to target this clinical problem effectively. Interested parties, both researchers and pharmaceutical partners are encouraged to reach out to Dr. Steinz.
For more information contact Maarten Steinz (m.m.steinz@amsterdamumc.nl) or read his scientific publications.
Researchers involved
Dr. Maarten Steinz, Amsterdam UMC
Prof. Dr. Conny van der Laken, Amsterdam UMC
Assoc. Prof. Dr. Jan van den Bossche, Amsterdam UMC
Dr. Anneke van der Kooi, Amsterdam UMC
Dr. Joost Raaphorst, Amsterdam UMC
Prof. Dr. Richard Jaspers, Vrije Universiteit Amsterdam and Amsterdam Movement Sciences (AMS)
Assoc. Prof. Dr. Johanna Lanner, Karolinska Institutet's Department of Physiology & Pharmacology
Text: Esmée Vesseur and Maarten Steinz