Vinnova Funding to Precision Medicine in Rheumatoid Arthritis
Photo: Karolinska Institutet
Vinnova, Sweden’s innovation agency, recently funded eleven innovation environments in
precision medicine across the country. Professor Per-Johan Jakobsson, Group Leader at CMM, is the project leader and contact person for one of the three funded environments at Karolinska Institutet.
The project is called “Prevention and early therapy of rheumatoid arthritis using precision medicine”. The partners are Karolinska Institutet, Region Stockholm (where Karolinska Universitetssjukhuset and Centrum för Reumatologi are involved), Thermo Fisher Scientific, Elsa Science and Uppsala University. At Karolinska Institutet Per-Johan Jakobsson is the principal investigator for the project, with support from Lars Klareskog and Dr Martina Johannesson who is the project coordinator. They will receive SEK 20 million for 2.5 years that will be distributed between the different partners. CMM News met Per-Johan through Zoom for a short interview.
Where are we at today when it comes to the use of precision medicine in diagnostics, treatment and prevention of rheumatoid arthritis (RA)?
“We are at the beginning of the new era. We can identify individuals at high risk of developing rheumatoid arthritis (RA), using information such as serology (mainly identification of antibodies through blood samples), environmental risks like smoking, certain musculoskeletal symptoms and genetics. In our risk cohort (a group of individuals who are at very high risk of developing disease) close to 40% of the included individuals develop RA within 2 years. Now, with this project, we are going one step further and we actually like to use the term “precision prevention”. Recent data show that treatment of high-risk individuals with the T-cell inhibiting antibody Abatacept (commonly used treatment for moderate to severe RA) delayed and potentially prevented the development of RA in those individuals (Rech J et al., 2021, ACRabstracts.org). With data and knowledge gathered so far, there is thus a promising future for precision prevention medicine in RA.”
What is the plan for “Prevention and early therapy of rheumatoid arthritis using precision medicine” with the funding from Vinnova?
“Our RA research is already an innovation environment where we integrate quality registers, clinical as well as molecular data. The project that Vinnova has invested in is a natural continuation for us. We will use a web-based screening test “Rheumatic?” and an application for self-monitoring under development by one of the project partners, the e-health company Elsa Science. If the answers in “Rheumatic?” by a study participant matches with inflammation-like musculoskeletal symptoms, the persons will be asked to leave samples for genetic and serological analysis using diagnostic tests developed by another company-partner, Thermo Fisher Scientific. Then the person gets to see a doctor. Through the app for self-monitoring, the study participants will be able to track their symptoms and eventually share them with health-care. If the subsequent results identify the person to be at high risk for developing RA, the person will then be followed by the rheumatologists involved in the study and may also be included in clinical trials for prevention of RA. These tools will provide a coherent system that supports not only precision prevention of RA, but also enables rapid diagnosis and very early therapy for those who develop arthritis despite our prevention efforts. Today the average time from getting arthritis to receiving first treatment is 6 months. By applying the methods in this project, our goal, in addition to preventing the disease, is to be able to give the patients targeted treatment very soon after the first episode of arthritis. Our biggest goal of the project, however, is prevention.”
Large Investment in Precision Medicine
Richard Rosenquist Brandell
Photo: Rick Guidotti
Genomic Medicine Sweden (GMS) has received 220 million SEK for continued introduction of precision medicine into Swedish healthcare. Through Sweden’s innovation agency Vinnova, the Swedish government has invested SEK 96 million in GMS and Swedish regional health authorities and universities have added another SEK 124 million.
Richard Rosenquist Brandell, Group Leader at CMM, is the director of the Swedish national infrastructure Genomic Medicine Sweden (GMS), launched in 2018. The aim of GMS is to translate innovation in genomics into clinical practice and to implement a sustainable infrastructure for precision medicine in Sweden. Precision medicine a more personalised approach to healthcare, seeking to take into account individual variability in genes, environment, and lifestyle for each person. The individual patient can thus be more effectively diagnosed and treated with a reduced risk of short and long-term side-effects.
GMS has coordinated development and implementation of genomic technologies for clinical use in healthcare throughout Sweden. By performing broad gene panel and whole-genome sequencing these tests detect genetic variations in cancer and rare diseases, that in turn improve diagnostics, treatment and follow-up of the patients. In all Swedish regions with university healthcare, there are now established regional Genomic Medicine Centers (GMC). A national genomics platform has been developed to enable the analysis and sharing of huge amounts of data in a harmonized and secure way. The genomic platform is also an important resource for research and development of new, targeted drugs. During the upcoming phases, GMS will also focus the work on linking the refined genetic diagnostics to clinical studies.
The aim of the recent funding of GMS is to contribute to the ongoing introduction of precision medicine into healthcare, strengthening Swedish research and promoting new research and innovation collaborations between industry, healthcare and academia. The long-term goal is that eventually every individual in Sweden should have access to personalised and more precise diagnostics and treatment.
Albin Björk is Awarded the Swedish Rheumatological Association's Prize for Best Dissertation
Photo: Saga Rebecka Herlenius
The CMMer Albin Björk won the Swedish Rheumatological Association's (SRF) prize for best dissertation in 2021. His thesis, "Immunopathogenic mechanisms in primary Sjögren's syndrome", was focused on the characterization of exogenous and endogenous factors contributing to the immunopathology of the autoimmune disease primary Sjögren’s syndrome.
In the studies included in the thesis, Albin Björk and colleagues found that cigarette smoking does not appear to increase the risk of the disease, but that it may instead be a protective factor. A history of infections, however, was associated with a higher risk of development of Sjögren’s syndrome.
When studying lymphocytes from patients with Sjögren’s syndrome, they found aberrances in B cell gene expression patterns and dysregulation of the CXCR5/CXCL13 axis, which is important for lymphocyte migration.
In the thesis, Albin and his co-authors also found additional support for the hypothesis of infections as an environmental risk factor for systemic autoimmune disease. They did so by testing serological and cellular responses against viral antigens in patients with systemic autoimmune disease on no or mild treatment and found that the patients developed higher levels of virus-specific antibodies compared to healthy controls.
Albin Björk defended his thesis on April 23rd 2021 with Marie Wahren-Herlenius and Alexander Espinosa as supervisor and co-supervisor, respectively. Currently he is working as a physician at the Center for Rheumatology, which is a part of the Academic Specialist Center, and will continue his research on rheumatic diseases in parallel.
38 million SEK to Per Svenningsson’s Research on Parkinson’s Disease
Per Svenningsson, Group Leader at CMM, has received funding from Nordstjernan Holding AB and Axel Johnson Group consisting of 38 millions SEK for five years.
The purpose of the funding is to support Per Svenningsson’s research on basic mechanisms in the pathogenesis of Parkinson’s disease as well as the search for a future tailored treatment slow down disease progression.
Read more: Karolinska Institutet press release
Per Svenningsson. Photo: Ulf Sirborn.
CMM Researchers Find That Autoantibodies Are Possible Contributors in Causing Fibromyalgia
Emerson Krock. Photo: Private
Camilla Svensson. Photo: Ulf Sirborn
Emerson Krock, Postdoc, and Camilla Svensson, Professor and Group Leader, are co-first and last authors, respectively, of a recent publication in the Journal of Clinical Investigation, showing that autoantibodies are possible contributors to fibromyalgia, a disorder characterized by chronic widespread pain in muscles and bones.
Researchers at Karolinska Institutet, King’s College London and the University of Liverpool, UK conducted the study as a collaboration.
The results pave the way for new approaches to the treatment of fibromyalgia.
Read more: Karolinska Institutet press release
“Passive transfer of fibromyalgia symptoms from patients to mice,” *Andreas Goebel, *Emerson Krock, Clive Gentry, Mathilde R. Israel, Alexandra Jurczak, Carlos Morado Urbina, Katalin Sandor,Nisha Vastani, Margot Maurer, Ulku Cuhadar, Serena Sensi, Yuki Nomura, Joana Menezes, Azar Baharpoor, Louisa Brieskorn, Angelica Sandström, Jeanette Tour, Diana Kadetoff, Lisbet Haglund, Eva Kosek, Stuart Bevan, *Camilla I. Svenssonand *David A. Andersson, Journal of Clinical Investigation, online 1 July, 2021, doi: 10.1172/JCI144201 (*co-first/last authors)
Nine CMM Researchers Receive Funding from the Swedish Brain Foundation (Hjärnfonden) 2021
Photo: Unsplash, Robina Weermeijer
The Swedish Brain Foundation awards scholarships and grants to researchers and research groups to enable or enhance important basic and clinical research regarding the central nervous system.
This year the following researchers from CMM received grants:
(Name, Project Title, Research Area)
Faiez al Nimer, Detailed characterization of immune cells in multiple sclerosis, with focus on EBV, MS and other neuroinflammatory diseases
Eric Herlenius, Inflammation, neural networks, breathing difficulties and inspiration!, The brain of children and adolescents
Jan Hillert, Individualized treatment of multiple sclerosis for optimal long term outcome, MS and other neuroinflammatory diseases
Maja Jagodic, Epigenetics: New functional and therapeutic applications in multiple sclerosis, MS and other neuroinflammatory diseases
Ingrid Kockum, Genetic and protein biomarkers for risk and severity of multiple sclerosis, MS and other neuroinflammatory diseases
Ann Nordgren, Genetic mapping of children with neurological disabilities without diagnosis, The brain of children and adolescents
Tomas Olsson, Risk genes and pathogenesis in multiple sclerosis, MS and other neuroinflammatory diseases
Fredrik Piehl, Is myelin repair a realistic possibility in multiple sclerosis?, MS and other neuroinflammatory diseases
Per Svenningsson, GBA-Parkinson disease as a target for precision medicine, ALS, Parkinson’s disease, Huntington and other neurodegenerative diseases
CMMers Receive StratNeuro Funding
Maja Jagodic. Photo: Karolinska Institutet
Bob Harris. Photo: Karolinska Institutet
The strategic research area neuroscience at Karolinska Institutet (StratNeuro) has awarded a total of 18 MSEK to six Collaborative Neuroscience Research Projects. Each project is funded with 3 MSEK.
Maja Jagodic and Bob Harris, both CMM Group Leaders and Professors at the Department of Clinical Neuroscience, have received funding for one collaborative project each. The purpose of the funding is to establish new collaborations.
Maja Jagodic was the main applicant for a project titled: "Targeting neuroinflammation and neurodegeneration using artificial ligands". The co-applicant was John Löfblom, Department of Protein Science, The Royal Institute of Technology (KTH).
Bob Harris, applied for funding of the project titled: "Novel immunotherapy targeting myeloid cells for neurological diseases: Drug repurposing and nanoengineering" and his co-applicant was Björn Högberg, Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
The strategic research areas are efforts by the Swedish government in certain selected areas that has been ongoing for more than ten years. Karolinska Institutet receives governmental strategic funding for six fields: stem cells, diabetes, neuroscience, cancer, epidemiology and health research.
StratNeuro has the mission to integrate clinical and basic research and to foster a new generation of leaders and scientists in translational neuroscience.
The external evaluator panel for the collaborative StratNeuro funding 2021 consisted of the following researchers:
David Engblom, Linköping University
Cecilia Lindberg, Lund University
Paolo Medini, Umeå University
Håkan Olausson, Linköping University
Åsa Petersén, Lund University
Mart Saarma, Helsinki University, Finland
Pontus Naucler Leads COVID-19 Vaccine Research Platform Funded by the Swedish Research Council
Pontus Naucler. Photo: Private
Pontus Naucler, researcher in Anna Färnert’s Group at CMM, will lead FASTER, a national COVID-19 vaccine research platform, one of six research environments awarded with a total of SEK 100 million from the Swedish Research Council.
FASTER will include register-based research and clinical trials as a basis for studying the immune response to the vaccines, as well as their safety and effectiveness.
This national platform will be a part of the large EU network called “VACCELERATE” which has the aim of evaluating ongoing and future vaccinations as well as making the process of clinical testing of vaccines faster in the future.
Strategic Research Funding for Germline Development Studies
Qiaolin Deng, Associate Professor and CMM Team Leader, is one of the six 2021 Junior Grant awardees in the Karolinska Institutet Strategic Research Area in Stem Cells and Regenerative Medicine. Qiaolin’s research team is interested in the developmental principles of the germline (the cells that pass on genetic information to the progeny, i.e. the egg and sperm) in health and disease and the title of the awarded project is ‘Revealing deleterious gene dosage effects on germline specification and testicular stem cell niche in Klinefelter syndrome by single-cell technology’. The project will be supported with 4 MSEK for 2 years.
Qiaolin Deng. Photo: Sanjiv Risal
Project picture: Genetic mouse models and in vitro hPG-CLCs differentiation of KS-iPSCs as tools to study global gene dosage effects.
Why did you choose germline development as your research niche and why is this research relevant?
“As a researcher, I have always been very inter-ested in the early development of the embryos, and the germline is the basis for this development. The development of the germline in an individual is in itself a process of continuous maturation that goes beyond puberty. There is intricate regulation at the molecular level involved in this process. Many cases of non-heritable variation involve germline epigenetics, and these are questions that have not been extensively studied before. The epigenetic regulation influences the development at all levels, also processes such as clonality and migration of the germ cells. Over the past few years new technological advances have made it possible to study these questions with a deeper resolution. When I chose my research focus, I also caught the moment of technology advancement.“
Klinefelter syndrome is caused by the presence of at least one additional X-chromosome in the male. There are few distinguishing features of the syndrome before puberty which makes early diagnosis difficult. However, after puberty, the testicular environment starts to degenerate and sperm can usually not be produced as a result. Thus, one of the main features of the syndrome is male infertility.
Can you briefly explain the aim of the project for which you were awarded the Junior Grant?
“In the present project we will use Klinefelter- derived iPS cells*. We want to study how the extra chromosome influences germline devel-opment. Persons with Klinefelter syndrome suffer from infertility but it is not because they lack the germ cells from the beginning. At the start of puberty, the germ cell pool is still there however, there is a “toxic” process in the testicular environment that starts at puberty in individuals with Klinefelter syndrome. We ask the question why the extra X chromosome does not do much harm initially. What is the impact of gene dosage and allelic gene expression on germ cell maturation? I always think about allelic expression since my postdoc projects were focused on that. Our preferred method in this project is single cell sequencing and at CMM we have a great core facility for that!”
With whom do you collaborate?
“Our main collaborators are Jan-Bernd Stukenborg at KBH, KI (his team works on fertility preservation) and at CMM we collaborate with Ning Xu Landén in the single sequencing studies of wound healing.”
What is the relevance of these studies from a patient/public health perspective?
“Klinefelter syndrome is estimated to occur as frequently as 1 in 600 births, thus contributing significantly to male infertility on a population level. Even though our research is very basic, I would say that one ambitious goal is to be able to find ways to save their fertility earlier. We strive to do that by understanding the molecular mechanisms of their germline development better.”
*The iPS cells (induced pluripotent stem cells) originate from skin biopsies from patients with Klinefelter syndrome. The fibroblasts are then re-programmed back to an embryonic state. This helps us to study human disease in a better way.