Knee pain and Chronic inflammatory conditions like Osteoarthritis are the leading cause of global disability and one of the most expensive conditions to treat by healthcare professionals, especially when joint replacement surgery is required [1,2]. Given that the prevalence of this disease in adult populations is increasing, there are strong economic and personal motivations for finding new interventions that can have a positive impact over conventional treatment plans.
A new autologous biologic called Autologous Cytokine-Rich Serum (ACRS) may offer a promising solution to ward of joint replacement surgery for conditions like OA by solving the problem of chronic inflammation.
Controlling the anti-inflammatory cascade
Now, in healthy individuals the body maintains a state of equilibrium in special messenger proteins (cytokines) that control the inflammatory process. These cytokines dock onto corresponding signal sites of tissue cells and transmit messages to "trigger inflammation" or "stop inflammation" in response to environmental triggers. Chief among these are the pro-inflammatory cytokines interleukin-1 (IL-1) and it's natural anti-inflammatory antagonist interleukin-1 receptor antagonist (IL-1Ra).
You can watch how these two cytokines compete with one another to control inflammation here: Cytokines biological principle
Osteoarthritis and other chronic inflammatory conditions are characterized by an imbalance in the number of anti-inflammatory and pro-inflammatory cytokines - tipping in favour of the latter. In this case, the pro-inflammatory cytokines like IL-1 causes the breakdown of cartilage which in turn triggers more inflammation, pain, and so on and so forth in perpetuity. Osteoarthritis with no end in sight.
Autologous Cytokine-Rich Serum (ACRS) is a biologic created from whole blood and processed to be enriched with high concentrations of the anti-inflammatory cytokine, IL-1Ra. It was developed on the idea that by delivering a high dose of IL-1Ra to a site of chronic inflammation, you can correct the imbalance between these two competing cytokines. This is because IL-1Ra occupies specific synapses - or signal sites of the cells - on cartilage cells to prevent the damaging protein IL-1 from binding to these areas and triggering more inflammation. Again, the video linked above illustrates this process for you.
Real-world impact
Now how does the scientific model of ACRS stack up in the real world when patients are being treated? Well, research is sparing when compared to other autologous biologics like PRP, but preliminary results appear very encouraging with respect to it's ability to reduce inflammation and pain in patients with minor to moderate knee OA over 6 to 12 months.
For the purposes of evaluating the best literature, I will put animal models and non-comparative trials aside and focus on 3 Randomized Control Trials (RCTs) treating a total of 245 patients with ACRS (150 w/ saline control) [3,4,5].
2 of these 3 RCTs found significant improvements in primary outcome measurements (WOMAC), and all three found significant improvements in secondary outcome measurements (VAS) from baseline to follow-up. These are all patient-reported clinical outcomes so their relevance for how patients feel they have responded to treatment is high.
With respect to the safety of this new biologic, none of the RCTs found evidence of severe adverse events related to the use of ACRS which is in line the historical high tolerability and safety of autologous products.
Future applications of ACRS
With consideration to the above results involving the use of ACRS for knee OA, there is good reason to be enthusiastic about this new intervention for patients that have failed conventional treatment plans or do not have access (or the desire) for surgical intervention. What's more is that the mechanism in which IL-1Ra disrupts the inflammatory cascade suggests that it may be effective at controlling inflammation in other pathologies outside of knee OA depending on their clinical presentation.
There is a lot more we can talk about regarding ACRS, such as the different types (which is critical), injection protocols, and how it stacks up against other autologous biologics like PRP. While I plan to dive into these topics in the future, feel free to leave a comment if this is something you're interested in discussing over the virtual water cooler.
References and Additional Reading
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1789-1858
Arthritis Data and Statistics. Centers for Disease Control and Prevention (CDC). Feb 2020.
Auw Yang KG, Raijmakers NJ, van Arkel ER, et al. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis Cartilage 2008;16:498-505.
Baltzer AW, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage 2009;17: 152-160.
Kon E, Engebretsen L, Verdonk P, Nehrer S, Filardo G. Clinical outcomes of knee osteoarthritis treated with an autologous protein solution injection: A 1-year pilot double-blinded randomized controlled trial. Am J Sports Med 2018;46:171-180.
This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and any related subjects. The views and opinions expressed in this post are those of the author and may not reflect the views and opinions of MDBiologix. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if any treatment is right for you.