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Restoring Balance, Developing a Cure
Posted on October 9th, 2017 by Tiffany Chen, PhD in Pharma R&D
Over the past two decades, significant progress has been made in the treatment of a range of autoimmune disorders and today thousands of patients enjoy an improved quality of life as a result. However, current therapeutic approaches to autoimmune disease are either generally or specifically immunosuppressive (e.g., IVIG infusions, methotrexate, JAK inhibitors, anti-TNF antibodies, anti-CD20 targeted antibodies), exposing patients to an increased risk of opportunistic infection and hematological cancers. Up to a third of patients with the tractable disease still fail to respond to treatment, and most will ultimately lose response. In many cases, effective treatments don’t exist at all.
While the etiology of most autoimmune disease remains murky, it is generally understood to be a loss of self-tolerance. In principle, restoration of peripheral tolerance should provide patients with a full or partial “cure,” and as such, a wide variety of academic and commercial organizations have been pursuing research in this area for many years. Approaches have included oral or injectable proteins and peptides, nanoparticle carriers, antibody-like constructs, and engineered T-cells.
The ideal disease for peripheral tolerance restoration is one where the pathogenic antigen is well known, dominant, and readily delivered to the appropriate biological compartment for processing and presentation. There are several examples described in the literature, including but not limited to multiple sclerosis, neuromyelitis optica, myasthenia gravis, membranous glomerulonephritis, pemphigus vulgaris, and the most well-known: type 1 diabetes mellitus (T1DM).
T1DM is a well-known and highly prevalent autoimmune disease characterized by an autoimmune attack on pancreatic beta cells, the subsequent loss of an ability to control blood sugar, and the long-term destruction of microvasculature resulting in the failure of critical organs and tissues. The disease is generally considered pediatric, with a diagnosis generally made by the age of ten. However, there is a second, potentially much larger population of adults who present with later onset disease and are often misdiagnosed as having type II diabetes. The restoration of peripheral tolerance for patients with a viable population of remaining beta cells would blunt the progression of a disease, improve patient quality of life, reduce the incidence and severity of long term sequela, and ameliorate the overall burden on the healthcare system.
At Rubius, we believe that a red cell-based antigen-presenting platform represents a powerful and specific way to deliver tolerogenic antigen to the appropriate biological compartment. Importantly, the Red-Cell Therapeutics (RCT) system we have developed at Rubius can evaluate multiple antigens identified to be relevant in specific autoimmune diseases including diabetes. These can be tested individually or even as co-expressed combinations. Furthermore, we can test extracellular or intracellular auto-antigen expression as desired. Our emerging data in a variety of mouse model systems suggests that this may be one of the most effective ways to one day realize a potential cure for patients.
It is a very exciting time for the autoimmune team here at Rubius as we develop a new class of life changing medicine.
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Tiffany Chen, PhD
Principal Scientist, Rubius Therapeutics