She wants to end the pain
There is currently no cure for rheumatoid arthritis, a disease that can cause severe pain. Rheumatologist Anca Catrina is trying to find a way to prevent the symptoms of the disease and indeed to prevent it breaking out at all.
Name: Anca Irinel Catrina
Title: Professor of rheumatology at Karolinska Institutet’s Department of Medicine, Solna and consultant at the rheumatology clinic at Karolinska University Hospital.
Age: Recently celebrated her 46th birthday.
Family: Husband and 13-year-old daughter.
How I relax: I like to listen to music. Normally piano pieces, with a particular fondness for the composer Rachmaninov. Other forms of relaxation include reading and cooking.
Scientific role model: My previous supervisor, Lars Klareskog.
The best thing about being a researcher: Finding the answers to previously unanswered questions.
It is a dark, rainy afternoon when I meet Professor Anca Catrina, who is dressed in a bright red jacket and offers a much-needed cup of coffee. She explains that her interest in rheumatology was awakened during her time as a medical student in Bucharest.
“I found the detective work so exciting, trying to understand what was going on,” says Anca Catrina.
Today, she leads a research group of 20 members, in which one person sticks out for her completely unique expertise.
“My group includes what we call a research partner, someone who has suffered from rheumatoid arthritis for many years. Her experience and thoughts are extremely important, as we want to include the patient’s perspective in our research,” says Anca Catrina.
“Involving patients in this way is fairly new.”
As an example, the research partner has helped to formulate relevant survey questions and also pointed out the benefits of patients being able under certain circumstances to order tests without visiting the doctor.
In Sweden, approximately one person in every hundred suffers from rheumatoid arthritis (RA). Women are diagnosed more often than men and in adulthood the disease is most likely to strike between the ages of 50 and 60. The disease causes bone and cartilage in joints to gradually deteriorate and there is currently no cure. There is still much that remains unknown about the mechanisms behind why certain individuals suffer from the disease.
“I am interested in how the disease arises and whether it might be possible to prevent it and thus avoid the suffering it causes,” says Anca Catrina.
At the moment, the disease is usually not diagnosed until it manifests itself in the form of swollen and inflamed joints.
“However, prior to this stage, many people may already have lived with pain for months or years and feel weary, so the process may be underway for a long time before the joints swell,” explains Anca Catrina.
One clue that RA may be responsible is that the body builds specific antibodies that can be measured by blood tests.
“The presence of these antibodies in the blood signals that something is happening and that the person suffering from joint pain may be at increased risk of subsequently developing RA, while the risk is much less if the antibodies are not present in the blood,” she says.
These specific antibodies are called anti-citrullinated protein antibodies (ACPAs). Research has shown that if these antibodies are isolated from the blood of RA patients and given to healthy mice, the formerly healthy mice will suffer from bone loss and pain. Bone loss is a result of the effect of the antibodies on cells known as osteoclasts, which are involved in the normal breaking down of bone tissue, making them more active.
“In humans, these antibodies may be present in the blood up to 10 years prior to the outbreak of the disease,” says Professor Catrina.
Population studies covering large groups of people have previously shown that smoking is one environmental factor that increases the risk of suffering from RA.
“However, one doesn’t smoke with the joints but with the lungs. This is why we want to study what happens there, to see if this offers any clue to how the disease begins,” says Anca Catrina.
That smoking, and even other forms of air pollution, increases the risk of RA might indicate that these particles cause a reaction in the lungs that triggers the RA process in certain individuals.
“A large proportion of smokers experience changes in mucous membranes in the lungs and mouths but not all of them develop RA, so increased susceptibility is also required,” says Anca Catrina.
As yet, it is not entirely clear why the immune system in the lungs reacts in such a way that ACPAs are formed.
“However, antibodies then make their way through the bloodstream to the joints and, in the next stage, contribute to the stimulation of osteoclasts and immunological signalling agents such as IL-8, which lead to bone damage and pain,” explains Anca Catrina.
Part of her research is aimed at identifying those at high risk of developing RA before the disease breaks out. One of the goals is to create better tools for making risk assessments as reliable as possible. As a supplement to studying biological markers such as ACPAs, the group therefore intends to develop a matrix with various questions. These may deal with the subject’s gender, whether they are a smoker or non-smoker, or whether they suffer from joint pain. Depending on their answers, respondents can then be divided into various risk categories.
One way to identify those at risk is via the website reumatiskt.se/ontilederna. This was created in 2015 and allows those experiencing symptoms to take a joint pain test. Anca Catrina also runs a clinic in Solna with approximately 100 patients referred from primary healthcare. Similar clinics have also opened at Karolinska University Hospital in Huddinge and at the newly opened Centre for Rheumatology, where Anca Catrina is research manager. Plans are now in place to open similar clinics in Gothenburg, Linköping, Örebro and Umeå.
She is keen to emphasise that not all of the individuals at risk will go on to eventually develop RA.
“It is also important to us that we are able to identify those at very low risk of becoming sick, so that we can say to them, “you have a very low risk of developing the disease,” says Anca Catrina.
Anca Catrina has recently obtained two substantial research grants, including an ERC Consolidator Grant, awarded to prominent researchers who show great promise in their scientific career.
“It feels great to receive this [award] after all these years. Now we would really like to give something back to patients. The aim is to see if we can provide those at increased risk with treatment to protect bone tissue,” she says.
To this end, a group of patients at increased risk of suffering from RA will be treated with bisphosphonates, a class of drugs commonly prescribed to treat osteoporosis. Such drugs are currently prescribed to patients such as women undergoing the menopause. During the new study, half of patients will receive these drugs while half will receive a placebo. After one and twelve months, researchers will measure levels of pain in participants, as well as imaging bone loss and monitoring the development of RA. The study will include 60 subjects and will commence during 2018.
When asked to name one important characteristic in a good researcher, Anca Catrina highlights stubbornness. This attitude to work is also reflected in her motto, a quote from the author Franz Kafka: “So if you find nothing in the corridors open the doors, and if you find nothing behind these doors there are more floors, and if you find nothing up there, don’t worry, just leap up another flight of stairs. As long as you don’t stop climbing, the stairs won’t end, under your climbing feet they will go on growing upwards.”
To keep one’s eyes on the prize, despite adversity, is a character trait that may come in very useful, not least given her wish to contribute to the development of new drugs.
“Here there are many different points of attack. One is to block the immunological pathways that contribute to bone loss. Another is to develop some kind of vaccination to make the immune system less sensitive to the changes that lead to the production of ACPAs in receptive individuals,” says Anca Catrina.
Anca Catrina about...
I love sashimi and am more than happy to eat it several times a week. However, I have yet to eat the dish in Japan itself. That trip is high on my list of things to do, ideally with my family.
As individual researchers, we have a responsibility to be thorough and transparent whenever we publish our results. And we all need to be sufficiently ethical to allow us to disclose any lack of ethics.
...best character trait as a researcher
Aside from the necessary curiosity, my stubbornness – to never give up even in the face of great adversity. However, stubbornness isn’t always a good trait, just ask my husband...
My entire family comes from Rumania and I met my husband there when we were young doctors. Rumania has provided me with an identity I am proud of, even if I primarily feel like a European.
Text: Lotta Fredholm, first published in Swedish in Medicinsk Vetenskap nr. 1, 2018.