Injections are often required for lifelong treatment of chronic diseases such as rheumatoid arthritis. Patients skip doses due to fear of needles, infection from injections and pain. This encourages the development new delivery strategies which combine efficacy and minimal side effects.
Researchers from Baylor College of Medicine, along with other institutions that collaborated on the project, have investigated a new way to deliver medications. They found a method of delivery which does not require injections and could be as simple as swallowing pills. The study was published in Proceedings of National Academy of Sciences.
Professor of integrative biology at Baylor, Dr. Christine Beeton is the co-corresponding author. In the current study, we investigated the possibility of using Lactobacillus Reuteri as an oral drug delivery platform for treating rheumatoid arthritis in an animal model.
In previous work, the Beeton laboratory had demonstrated that a short protein derived from sea-anemone toxins reduced disease severity in rats models of rheumatoid arthritics and patients with plaques psoriasis. Beeton explained that peptide therapy requires multiple injections which reduces patient compliance. Direct oral delivery is also not very effective.
Beeton teamed up with Dr. Robert A. Britton. He is a professor of molecular microbiology and virology at Baylor and a member of their Dan L Duncan Comprehensive Cancer Center. Britton’s lab has developed tools and expertise for genetically modifying probiotic bacteria in order to release compounds. In this study, the team genetically modified the probiotic L.reuteri so that it secreted peptide ShK235 derived sea anemone toxic.
The bacteria were chosen because they are found in the guts of humans and animals. It’s one of the lactic-acid bacteria groups, which has been used in the food industry for a long time as a cell manufacturer. The U.S. Food and Drug Administration recognizes it as safe. L. reuteri is safe for infants, children and adults. It’s even safe in immunosuppressed populations.
Beeton stated that the results were encouraging. The daily delivery of the bacteria called LrS235 dramatically reduced the clinical signs of arthritis, including joint swelling, cartilage damage and bone destruction in an animal model.
Researchers followed bacteria LrS235 secreting ShK-235 inside animal models. After feeding rats LrS235 which releases ShK235, the researchers were able to detect ShK235 in blood circulation.
The bacteria are not permanently present in the gut, which is another reason why we chose L. Reuteri. The bacteria are removed when the inner surface of the gut is regularly renewed, Beeton explained. This opens up the possibility of regulating treatment administration.
Researchers anticipate that this new drug delivery system could ease treatment for patients in future. Beeton stated that bacteria could be stored inside capsules which can be kept in the kitchen. The capsules could be taken on vacation by a patient without needing to carry needles or refrigeration. They can continue their treatment without having to administer daily injections.
The findings suggest an alternative strategy for the delivery of peptide-based medications and that these techniques and principles could be applied to a wider range of drugs, and in the treatment of chronic inflammation diseases.
Joseph M. Hyser, Jacob L. Perry and Duolong Zhu are also contributors. The authors are associated with Baylor College of Medicine, Pana Bio, Inc., and Ambiopharm Inc.
The project was partially funded by the Alkek Center for Metagenomics and Microbiome Research and Bridge Funding at Baylor College of Medicine. The work was also supported by the Cancer Prevention and Research Institute of Texas, the National Institutes of Health, the Dan L Duncan Comprehensive Cancer Center, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.
