Patients experience
Peter Böhm
I myself had severe osteoarthritis (OA) in both hip joints, resulting in increasing pain that only got better for a short time, even with medication. In the end, I had to have endoprostheses fitted on both sides, first on the left and a few years later on the right. While the first surgery was successful and I was able to resume my job after a two-month break and also the pain in my left hip largely disappeared, the second surgery caused problems. Three weeks after the right hip surgery, I developed a wound infection, requiring emergency surgery with replacement of the endoprosthesis (two operations within three weeks) and a three-month course of strong antibiotics. The consequences included a delayed healing process, significantly longer absence from work than before and more severe problems when returning to work. Even today, almost two years later, I still have pain in my right hip from time to time and am more restricted on the right side than on the left.
The development of advanced therapies for the prevention of joint destruction caused by osteoarthritis and of the above-mentioned disease impact would be a great help to those affected. Even a significant reduction in the need for operations and joint replacements would make a meaningful difference.
How the Proto project can help OA patients
It is estimated that around 16% of all adults worldwide are affected by osteoarthritis, with knee and hip joint osteoarthritis being the most prevalent forms.
Life with osteoarthritis is associated with many restrictions for those affected. The disease leads to increasing destruction of the affected joints and means loss of mobility and functional capacity, combined with constant pain, joint swelling and stiffness. These symptoms also lead to considerable restrictions in working life, everyday life and leisure activities, including withdrawal from social contacts and isolation. Osteoarthritis is usually triggered by injuries to the affected joints – including very minor ones – which can lead to cartilage and bone damage, accompanied by low-grade inflammation within the joint. To date, there is no therapy to effectively combat or at least significantly slow down these harmful joint processes. Joint operations and artificial joint replacements can provide relief, but are associated with risks and do not always lead to lasting improvement. The development of innovative, effective therapies that intervene before osteoarthritis develops is therefore of crucial importance.
The international PROTO research consortium is using a two-pronged approach to combat osteoarthritic inflammation in the knee joint at an early stage and thus prevent progressive joint destruction – with the ultimate goal of improving quality of life for the millions affected worldwide.
Treatment approach 1
The first treatment approach developed as part of PROTO for the prevention of knee OA is a cell therapy approach based on newly developed advanced biological technologies. A single injection of PLX-PAD cells – anti-inflammatory cells derived from human placental tissue – is administered directly into the knee joint of patients with early-stage OA. The aim is to halt the progression of osteoarthritis at an early stage, before significant joint damage occurs.
Treatment approach 2
The second PROTO treatment approach involves special exercise training that patients at risk of knee OA after anterior cruciate ligament surgery can do at home. The first step is to identify patients who exhibit an abnormal gait pattern after surgery, which can subsequently lead to the development of osteoarthritis of the knee joint. This gait analysis is carried out in a specially equipped movement laboratory at the Julius-Wolff-Institut, Charité – Universitätsmedizin Berlin. The affected patients are then offered the opportunity to take part in a newly developed training programme, which is carried out at home using a dedicated app and wearable sensors. During training, sensors attached to the leg transmit data to a smartphone app, which provides real-time feedback on exercise execution and technique. The aim is to permanently correct abnormal movement patterns in order to prevent the development of osteoarthritis in the knee.
Work areas and work plan – how everything is connected
Margret Schmid-Holl
PROTO’s work plan consists of six closely interwoven scientific work packages and two supporting work packages. The entire project is supported by research partners from the Deutsche-Rheuma-Liga.
The entire project is funded by the European Union and the European Executive Agency HaDEA and is regularly reviewed. Furthermore, an independent ethics committee only approves the studies on patients once it has verified that they are minimally burdensome for patients.
How PROTO activities are connected and how patient representative are involved in.
Work Package 1
In Work Package 1, project management ensures that all parts work together well, that everything is organized, and that the schedule and financial plan run smoothly. Project Coordinator Prof. Tobias Winkler, Charité Berlin, and INN-ACTA Siena, Italy, are leading WP1 activities.
Work packages 2 and 3 deal with people with early-onset knee osteoarthritis
In Work Package 2 – Production of PLX-PAD cell therapy, a special cell product is being produced that is intended to help inhibit inflammation in the knee, rebuild cartilage and thus heal early osteoarthritis. Participating research teams come from Pluri Biotech Ltd., Israel and the Charité Berlin.
In Work Package 3, an initial clinical study is testing this cell therapy. It will examine how safe this treatment is and how effective it is. Research teams from the Charité Berlin and Pluri Biotech, Israel, are participating, and the Rheuma-Liga research partner is also planned to participate.
Work areas 5, 6 and 7 research and measure how the body reacts to these interventions, or whether and how the therapies work.
Work package 5 uses blood and urine values in the laboratory to search for unknown characteristics of immune metabolism disorders and genetic characteristics in osteoarthritis patients. Research laboratories from the University of OULU, Finland, the Charité Berlin and Nordic Bioscience A/S, Denmark are involved.
Work Package 6 investigates how physical changes in osteoarthritis can be visualized early using MRI. An AI was trained to read the images. A research team from the Paracelsus Medical University, Salzburg, Austria, is working on this.
Work package 7 is conducting laboratory research to understand exactly how cell therapy works, particularly how it reduces inflammation and promotes healing. Here, too, teams from the Paracelsus Medical University Salzburg and the Charité Berlin are conducting research
In work package 4, people who have developed an incorrect movement pattern after a cruciate ligament tear and surgical reconstruction and who therefore have an increased risk of knee osteoarthritis are treated on a trial basis.
For this group of people, an individual sensor-based training program that runs via an app and can be completed at home is being developed and tested. Researchers from the Charité Berlin are working here with the IT company KTEC and were supported by the research partners of the DRL. Research teams from the Charité Berlin and Pluri Biotech, Israel, are participating, and the Rheuma-Liga research partner is also planned to participate.
Work area 8 is used for communication and patient involvement. Patient participation is encouraged and the project will be publicly explained. Here again INN-ACTA Siena, Italy is involved, but also the ReumaNederland Foundation and the research partners of the Deutsche-Rheuma-Liga. The entire project is funded by the European Union and the European Executive Agency HaDEA and is regularly reviewed. Furthermore, an independent ethics committee only approves the studies on patients once it has verified that they are minimally burdensome for patients.
How the KTEC’s App works
A personalised digital training programme to reduce inflammation and to correct of movement and gait in preliminary stages of knee osteoarthritis by using an app
Zeljko Glavac
Work package 4 deals with patients who are in the preliminary stages of knee osteoarthritis after an operation and develop a faulty movement pattern. This then will be analysed and a special patient-specific training programme will be put together, the re.Flex system. Sports scientists and physiotherapists are involved here in collaboration with the company Kineto Tech. The company has developed an app that is designed to help improve mobility, motor skills and strength, as well as alleviate pain. The app is needed to carry out the training programme at home. The programme is explained with the help of a digital assistant (3D avatar), which guides you through the programme. In the future the programme and the app should also be available to patients with statutory health insurance, and the aim is to obtain approval for funding from health insurance companies.
We, Zeljko Glavac, Margret Schmid-Holl and Peter Böhm, were involved in work package 4. Together with employees of Charité Berlin and the company Kineto Tech, which developed the training programme, we created patient information about the training programme in German and English language. As patient representatives and research partners, we try to present the very extensive project in a simple and layman-friendly way for patients and to explain many technical terms as simply as possible.
As a patient representative and research partner, I find the project very interesting and challenging. Osteoarthritis is a very common disease and any therapy and treatment to improve health is always good.
You have to live with the disease but not suffer from it.