EC-ACS, A new generation of ACS

For the treatment of osteoarthritis (OA) in horses.
With demonstrated high IL-1Ra levels and high IL-1Ra / IL-1β ratios.

IL-1Ra – nature’s own cure
An established method of treatment of OA is to stimulate the horse’s own white blood cells to form the naturally occurring anti-inflammatory protein IL-1Ra at high levels.

IL-1Ra acts as an inhibitor (antagonist) of IL-1β, the central pro-inflammatory mediator in the develop-ment of OA (1-2). At a sufficiently high concentration IL-1Ra outcompetes the effect of IL-1 β through blocking of the cell receptors, IL-1R.

IL-1Ra has several unique features:
– High binding affinity to the IL-1R
– Outstanding target specificity
– Low toxicity
– Relatively small molecular
weight (17 kDa)

Short half-life is a disadvantage and complicates management
An aggravating circumstance is, however, IL-1Ra’s short half-life (a few hours). Significant research resources have therefore been added to extend the therapeutic levels of the molecule. A review in 2013 reported twelve different approaches:

”In summary, the attempts made and the strategies that have been applied to extend the half-life and/or sustained release of IL-1Ra can be grouped firstly in to, those in which IL-1Ra has been fused and expressed with other proteins or peptides that  directly  increased the biological half-life of IL-1Ra, secondly, those in which IL-1Ra was encapsulated with drug delivering polymers that prolonged the sustained release of IL- 1Ra at target site.” (3)

Several methods for the same purpose have been published later (4-5). None of these methods are intended for intra-articular injection. They are administered systemically and will then rapidly be eliminated from the circulation.

”The main reasons for rapid elimination of proteinous drugs from circulation are enzymatic degradation, biochemical and/or biophysical clearance mechanisms. Therefore, IL- 1Ra being a small molecular weight proteinous drug is rapidly cleared from kidney by biochemical and biophysical clearance mechanisms.” (6)

Accordingly it is a clear advantage to administer high concentrations of IL-1Ra directly into the joint, thus delaying the degradation and excretion of the molecule. It has been shown in a study of post traumatic arthritis (PTA) (7).

EC-ACS – intra-articular injection with high IL-1Ra levels and high IL-1Ra / IL-1β ratios
Two veterinary ACS studies have shown that incubation of serum in specialized kits currently on the market offers the same levels of IL-1Ra as common serum tubes:

“Serum from blood incubated in plastic vacutainer tubes containing Z Serum Clot Activator contained similar levels of the cytokines and growth factors investigated as serum incubated in 2 specialised ACS containers. These results corroborate those of a previous study [Hraha et al], and indicate that cytokine production may be a consequence of whole blood incubation rather than an effect of specialised ACS containers.”

“Specialised ACS containers may not be necessary for preparation of a cytokine-rich serum.” (8,9)

The development work has been to obtain a method that results in significantly higher levels of IL-1ra in combination with high IL-1ra / IL-1 β ratios than before.

By defining a number of different factors the intended results have been obtained in this new product, EC-ACS. (Diagram 1 and 2)

During the work, it has also emerged how significant the actual procedure during ACS production is. It is therefore important to follow the instructions carefully.

A SAA test, EquiChek, is included and should be used on suspicion marked elevation of acute phase proteins, such as after surgery. Recommended maximum value <200 mg / mL, > 2 lines.

To slideshow  >>

EC-ACS Conditioning Device

 
It  requires a high level of receptor blocking with IL-1Ra to inhibit the pro-inflammatory signal.

 

Illustration-2_variant5_eng

Diagram 1. Concentration of TNF-α , IL-1β
and IL-1Ra after incubation in
Vacutainer and EC-ACS

diagram1_151007_utantext_engx

Diagram 2. ∆IL-1Ra / IL-1β ratio after
incubation in 24 hours

diagram2_151007_utantextx     

Web Production Liw Design
Top photo from Gemine.no