Rheumatoid Arthritis Treatment & Diagnostics: Addressing Unmet Need
Rheumatoid arthritis (RA) is an autoimmune disease affecting 1-3% of the world population. It is a chronic, systemic inflammatory disorder that affects multiple tissues and organs, but principally attacks flexible (synovial) joints, resulting in a painful condition and even disability if inadequately treated.
Treatment starts with the use of painkillers and anti-inflammatory drugs to suppress the symptoms. Patients may need to progress onto disease-modifying anti-rheumatic drugs (DMARDs) to inhibit the underlying immune process and prevent long-term joint damage. The latest generation of injectable biologic therapeutics offers the current last line of defence.
None of these current treatment options are aimed at early disease onset and they do not reduce inflammation propagation to other joints, or the incidence of flare-ups. The DMARDs and biologics in particular carry a risk of adverse side-effects associated with liver toxicity and the reduction of immune response, which leaves patients vulnerable to frequent infections.
ModiQuest has focused on developing therapeutic antibodies against the very earliest trigger for the aberrant autoimmune response that is fundamentally responsible for disease onset. The aim is to create a new, highly specific disease intervention treatment for both disease prevention and established RA, without any accompanying suppression of the immune system or liver toxicity.
ModiQuest RA Antibody Target
ModiQuest’s RA antibodies target the initial trigger for the autoimmune response that results in RA; citrullinated protein (see below). This is produced in response to a local inflammation resulting from injury or infection which causes cell death and the release of calcium ions. Calcium ions in turn activate a group of calcium dependent peptidylarginine deiminase (PAD) enzymes, which modify the arginine residues on proteins to citrulline. Citrullinated proteins then leak out of the dying cells and are exposed to the immune system, which responds with an inflammatory response, resulting in destruction of the joint tissue:
ModiQuest’s therapeutic antibodies were originally isolated from phage display libraries of RA patients, using the diagnostic target, CCP. These antibodies were used to hone in on the target epitope and to further refine and improve antibody specificity and efficacy. ModiQuest now has a group of human and mouse-derived therapeutic antibody candidates for RA treatment and a lead molecule, identified on the basis of affinity data.
ModiQuest RA Antibodies Reduce Arthritis Symptoms and Onset in Mice
- Reduces joint damage by over 70% vs untreated
- Over 10-fold reduction in arthritis score
- Halts disease progression for over 3 weeks after a single dose
- No observed side effects
Mouse efficacy data suggest that the therapeutic antibodies have the potential to be useful for both prevention of disease onset and treatment of established RA, by administering the drug only when needed. By using the marketed anti-CCP test to detect the onset of RA disease onset, these antibodies have the potential to be effective even before clinical symptoms have appeared.
For a full information package on ModiQuest’s rheumatoid arthritis antibody therapeutics programme, please contact Jos Raats at firstname.lastname@example.org, or call + 31 24 3614253.