Periodic Reporting for period 2 - SINPAIN (A game changer for the treatment of osteoarthritis: a cost effective combined advanced therapy to treat knee osteoarthritis)
Periodo di rendicontazione: 2023-11-01 al 2025-04-30
The SINPAIN project aims to provide new tools for the treatment and diagnosis of osteoarthritis (OA), a disease that affects more than 500 million people worldwide. Long considered a “wear and tear” condition of the elderly, it is now known that OA is a highly complex disease of the entire joint affecting a large proportion of the population under the age of 65. There is currently no cure for OA, and current treatment options are often costly and inefficient.
The contribution of SINPAIN to the management of OA focuses on three main aspects: 1) a product pipeline of safe, efficient and cost-effective therapies that could not only stop but reverse the course of the disease, 2) a new tool to support personalised diagnosis and treatment and 3) a comprehensive characterisation of the cells involved in OA’s pathogenesis. The new treatment combines novel RNA-based medicines that block molecular sources of inflammation and pain, an improved intraarticular hydrogel based on hyaluronic acid and smart delivery systems for anti-inflammatory drugs. If successful, SINPAIN technology will be instrumental in alleviating pain and slowing down disease progression for countless patients.
The contribution of SINPAIN to the management of OA focuses on three main aspects: 1) a product pipeline of safe, efficient and cost-effective therapies that could not only stop but reverse the course of the disease, 2) a new tool to support personalised diagnosis and treatment and 3) a comprehensive characterisation of the cells involved in OA’s pathogenesis. The new treatment combines novel RNA-based medicines that block molecular sources of inflammation and pain, an improved intraarticular hydrogel based on hyaluronic acid and smart delivery systems for anti-inflammatory drugs. If successful, SINPAIN technology will be instrumental in alleviating pain and slowing down disease progression for countless patients.
3 years into the project duration, SINPAIN has selected small interfering RNAs that silence the expression of IL1B and NGF (signals for inflammation and pain), defined prototypes of efficient vectors to deliver these siRNAs, and confirmed their safety and efficacy in cells. It has also produced modified hydrogels of hyaluronic acid that possess self-healing properties and that can be injected intraarticularly. Moreover, smart systems to slowly deliver the anti-inflammatory drug diclofenac in the joint have also been generated. The different prototypes have been combined in a single assembled product that constitutes the 1st Generation of SINPAIN therapeutics. All these developments are supported by an exhaustive analysis of the regulatory requirements and Quality-by-Design approaches to maximise their successful transition into clinics.
Simultaneously, significant efforts and coordination by the multidisciplinary SINPAIN team, is allowing a deeper understanding of the events leading to OA appearance. Specifically, they are depicting the contribution of the different cell types to the molecular changes that take place during OA pathogenesis by analysing human samples obtained during arthroplasty in knee with late OA. In parallel, co-culturing of relevant cell lines have been established in 3D scaffold to establish new model for OA conditions that will be tested on unique bioreactor to test the pipelines products developed in the project.
Complementary, artificial intelligence is being used to create a new tool to improve the diagnosis of OA. This is based on imaging techniques (magnetic resonance, computerised tomography and X-rays), from which relevant informative features have been successfully extracted allowing the discrimination between healthy and degenerated knees. In a further step, these will be used to distinguish different stages of the disease and allowing a more suitable medical management of each patient.
Finally, with the approval of the ethical committee, the first in vivo testing of the first generation of SINPAIN product has been currently tested on an animal OA model. The results are currently under treated to understand the effect of this new viscosupplement in early stage OA.
Simultaneously, significant efforts and coordination by the multidisciplinary SINPAIN team, is allowing a deeper understanding of the events leading to OA appearance. Specifically, they are depicting the contribution of the different cell types to the molecular changes that take place during OA pathogenesis by analysing human samples obtained during arthroplasty in knee with late OA. In parallel, co-culturing of relevant cell lines have been established in 3D scaffold to establish new model for OA conditions that will be tested on unique bioreactor to test the pipelines products developed in the project.
Complementary, artificial intelligence is being used to create a new tool to improve the diagnosis of OA. This is based on imaging techniques (magnetic resonance, computerised tomography and X-rays), from which relevant informative features have been successfully extracted allowing the discrimination between healthy and degenerated knees. In a further step, these will be used to distinguish different stages of the disease and allowing a more suitable medical management of each patient.
Finally, with the approval of the ethical committee, the first in vivo testing of the first generation of SINPAIN product has been currently tested on an animal OA model. The results are currently under treated to understand the effect of this new viscosupplement in early stage OA.
The decision making tool to aid in the diagnosis of OA is available online (https://restore-project.ru.is/database(si apre in una nuova finestra)). This new tool is a step forward in the available resources for OA diagnosis and has the potential to become a powerful tool for physicians, enabling them to personalize treatments based on individual patients' specific needs.