Personalized therapies and digital innovations to prevent disease progression
Osteoarthritis (OA) is one of the most prevalent joint disorders worldwide, affecting over 16% of the global adult population. This chronic and progressive condition, characterized by inflammation, pain, stiffness, and loss of joint function, is a leading cause of disability and reduced quality of life. Despite its widespread impact, there are currently no treatments available that can effectively modify the course of the disease, particularly in its early stages. It is within this context that the European Union-funded project PROTO (Advanced PeRsOnalized Therapies for Osteoarthritis) emerges, aiming to revolutionize OA treatment through innovative and personalized strategies. With a total funding of €7,447,875, PROTO represents a significant step forward in addressing one of the most pressing challenges in musculoskeletal health.
The PROTO project: a collaborative effort
Coordinated by Charité – Universitätsmedizin Berlin, one of Europe’s most prestigious medical and research institutions, PROTO brings together a multidisciplinary consortium of academic institutions, biotech companies, patient organizations, and industrial partners. The project, which officially began on January 1, 2023, and will run until December 31, 2027, is funded under the EU’s Health program (Grant Agreement ID: 101095635). The primary goal of PROTO is to develop advanced therapies for the prevention and treatment of OA in its early and pre-disease stages, with a particular focus on tackling inflammation, a key driver of disease progression.
Innovative approaches to combat osteoarthritis
PROTO adopts a dual-pronged strategy to address OA, targeting different stages of early inflammatory disease. The first approach involves the use of an innovative anti-inflammatory cell therapy called PLX-PAD, derived from placental cells. This allogeneic cell therapy product has demonstrated anti-inflammatory and regenerative properties in preclinical and clinical trials for other indications. In PROTO, early-stage knee OA patients will receive local injections of PLX-PAD, with the aim of reducing joint inflammation and preventing or even reversing cartilage degeneration. This marks the first time such a therapy is being tested specifically for early-stage OA, offering hope for a disease-modifying treatment.
The second approach focuses on patients in the pre-OA stage, particularly those recovering from anterior cruciate ligament reconstruction (ACLR). These patients often exhibit pathological gait patterns that can lead to the development of OA. PROTO introduces a personalized, sensor-based digital training intervention designed to correct these abnormal movement patterns. By restoring physiological movement and reducing mechanically induced inflammation, this intervention aims to prevent the transition from a healthy state to OA. This strategy is particularly innovative as it leverages digital tools to address biomechanical factors that contribute to joint degeneration.
Ambitious goals and objectives
PROTO is driven by a set of ambitious goals that aim to transform the way OA is understood and treated. One of the primary objectives is to investigate the safety and efficacy of PLX-PAD cell therapy in a randomized, double-blind, placebo-controlled Phase I/II clinical trial. This study will not only assess the therapeutic potential of PLX-PAD but also explore its mechanisms of action, particularly its impact on the local and systemic inflammatory status of patients. Cutting-edge biomarker studies, including immunological, metabolic, and genetic profiling, will accompany the clinical trials to provide a comprehensive understanding of the therapy’s effects.
Another key objective is to implement and evaluate the personalized sensor-based training intervention for pre-OA patients. By monitoring the influence of this intervention on joint inflammation and biomechanics, PROTO aims to establish a reliable and evidence-based approach to preventing OA development. Additionally, the project seeks to create a sustainable framework for tackling inflammation in OA, which can be applied in future therapeutic interventions.
A unique aspect of PROTO is its emphasis on patient involvement. The project includes a patient portal (BtP) designed to empower patients as active participants in the research and development process. This initiative aims to improve communication, engagement, and insights into the patient perspective, ensuring that the therapies developed are truly patient-centered.
The consortium: A network of excellence
The PROTO consortium is a testament to the power of collaboration, bringing together world-leading experts in OA research and treatment. The consortium includes four academic and university hospital institutions (Charité, Oulu University, Paracelsus Medical University, and Queensland University of Technology), one clinical-stage regenerative medicine company (Pluri), three SMEs specializing in clinical study support (NBS, KTEC, BtP), and two patient organizations (ReumaNL and DRL). This diverse network ensures that PROTO benefits from a wide range of expertise, from advanced therapy medicinal product (ATMP) manufacturing to biomarker analysis, metabolomics, and patient advocacy.
The project is led by Professor Tobias Winkler, Head of the Research Group for Advanced Musculoskeletal Therapies at Charité Berlin. With his extensive expertise in orthopedic and trauma surgery, Professor Winkler is well-positioned to guide this groundbreaking initiative.
Potential impact and future implications
PROTO has the potential to fundamentally change the way OA is treated, moving from symptom management to disease modification. By targeting inflammation and biomechanical factors in the early stages of OA, the project aims to halt or even reverse the structural and functional changes caused by the disease. If successful, PROTO could pave the way for new therapeutic options that prevent OA progression, significantly improving patient outcomes and quality of life.
Moreover, the integration of digital tools and patient-centered approaches sets a new standard for clinical research in musculoskeletal diseases. The insights gained from PROTO could also have broader implications for understanding the transition from health to disease in other chronic inflammatory conditions.
