中文
January 10, 2023
We are pleased to introduce the latest publication in PNAS with AmbioPharm CSO, Michael Pennington, PhD, and longtime collaborators at Baylor College of Medicine, where AmbioPharm synthesized the ShK peptide (ShK-235), derived from sea anemone toxin:
A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis
Significance
New therapeutics that combine efficacy with limited side effects and can be delivered noninvasively are needed to adequately treat patients with rheumatoid arthritis (RA) and other autoimmune diseases. Kv1.3 channel-expressing CCR7− effector memory T (TEM) lymphocytes are significant players in the pathogenesis of multiple autoimmune diseases, and blocking Kv1.3 reduces disease severity in rat models of RA and patients with plaque psoriasis. However, peptide therapeutics require repeated injections, reducing patient compliance. We used a bioengineered Lactobacillus reuteri as an oral delivery method of a Kv1.3 blocker for immunomodulation in rat models of atopic dermatitis and RA. This study demonstrates a novel approach for the noninvasive delivery of peptide-based therapeutics for the oral treatment of chronic inflammatory diseases.
Abstract
Engineered microbes for the delivery of biologics are a promising avenue for the treatment of various conditions such as chronic inflammatory disorders and metabolic disease. In this study, we developed a genetically engineered probiotic delivery system that delivers a peptide to the intestinal tract with high efficacy. We constructed an inducible system in the probiotic Lactobacillus reuteri to secrete the Kv1.3 potassium blocker ShK-235 (LrS235). We show that LrS235 culture supernatants block Kv1.3 currents and preferentially inhibit human T effector memory (TEM) lymphocyte proliferation in vitro. A single oral gavage of healthy rats with LrS235 resulted in sufficient functional ShK-235 in the circulation to reduce inflammation in a delayed-type hypersensitivity model of atopic dermatitis mediated by TEM cells. Furthermore, the daily oral gavage of LrS235 dramatically reduced clinical signs of disease and joint inflammation in rats with a model of rheumatoid arthritis without eliciting immunogenicity against ShK-235. This work demonstrates the efficacy of using the probiotic L. reuteri as a novel oral delivery platform for the peptide ShK-235 and provides an efficacious strategy to deliver other biologics with great translational potential.
Read on the publisher’s website: https://www.pnas.org/doi/10.1073/pnas.2211977120
Read more about the work on the Baylor Website: https://www.bcm.edu/news/a-promising-drug-delivery-method-could-replace-injections-with-pills
Citation: Wang, Y., Zhu, D., Ortiz-Velez, L. C., Perry, J. L., Pennington, M. W., Hyser, J. M., Britton, R. A., & Beeton, C. (2023, January 3). A bioengineered probiotic for the oral delivery of a peptide Kv1.3 channel blocker to treat rheumatoid arthritis. Proceedings of the National Academy of Sciences, 120(2). https://doi.org/10.1073/pnas.2211977120