Game-changing arthritis treatment replaces injections with pills

Treatment for chronic conditions such as rheumatoid arthritis often involves lifelong injections. (CREDIT: Creative Commons)

Treatment for chronic conditions such as rheumatoid arthritis often involves lifelong injections. Fear of needles, injection-associated infection, and pain are the causes of patients skipping doses, prompting the development of new delivery strategies that combine efficacy with limited side effects to adequately treat patients.

Researchers at Baylor College of Medicine and collaborating institutions have explored a better way to deliver drugs that doesn’t require injection but can be as simple as swallowing a pill. The study appears in Proceedings of the National Academy of Sciences.

“People don’t like having injections for the rest of their lives,” says co-author Dr. Christine Beaton, professor of integrative physiology at Baylor. “In current work, we have explored the feasibility of using the probiotic bacteria Lactobacillus reuteri as a novel platform for oral drug delivery for the treatment of rheumatoid arthritis in an animal model.”

Previous work from the Beeton lab has shown that a peptide or short protein derived from sea anemone toxin effectively and safely reduces disease severity in rat models of rheumatoid arthritis and in patients with plaque psoriasis. “However, peptide treatment requires repeated injections, which reduces patient compliance, and direct oral delivery of the peptide has low efficacy,” Beaton said.

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Beaton joined forces with Dr. Robert A. Britton, professor of molecular virology and microbiology and member of the Dan L. Duncan Comprehensive Cancer Center at Baylor. Britton’s lab has developed tools and expertise to genetically modify probiotic bacteria to produce and release compounds. In the current study, the team bioengineered the L. reuteri probiotic to secrete the ShK-235 peptide derived from the sea anemone toxin.

They chose L. reuteri because these bacteria live in the intestines of humans and other animals. It is one of a group of lactic acid bacteria that has long been used as a cell factory in the food industry and is recognized as safe by the US Food and Drug Administration. L. reuteri has an excellent safety profile in infants, children, adults, and even immunocompromised individuals.

“The results are encouraging,” Beaton said. “Daily delivery of these peptide-secreting bacteria, named LrS235, dramatically reduced the clinical signs of the disease, including joint inflammation, cartilage destruction, and bone damage in an animal model of rheumatoid arthritis.”

The researchers monitored the LrS235 bacteria and the ShK-235 peptide she secretes inside an animal model. They found that after feeding rats live LrS235 releasing ShK-235, they could detect ShK-235 in the bloodstream.

“Another reason we chose L. reuteri is because these bacteria don’t stay in the gut all the time. They are removed as the intestine regularly renews its inner surface layer to which bacteria attach,” Beaton said. “This opens up the possibility of regulating prescribing.”

Supernatants from LrS235, but not from LrGusA, block Kv1.3 currents and inhibit the proliferation of human CCR7-TEM cells. (CREDIT: PNAS)

More research is needed to bring this new drug delivery system into the clinic, but the researchers expect it could make it easier for patients to manage in the future. “These bacteria can be stored in capsules that can be kept on the kitchen counter,” Beaton said. “The patient can take the capsules while on vacation without the need for refrigeration or carrying needles, and continue treatment without the inconvenience of daily injections.”

The findings suggest an alternative peptide-based drug delivery strategy and suggest that such methods and principles can be applied to a wider range of drugs and the treatment of chronic inflammatory diseases.

LrS235 halts disease progression and reduces bone and joint damage and inflammation in rats with collagen-induced arthritis. (CREDIT: PNAS)

Other contributors to this work include Yuqing Wang, Duolong Zhu, Laura S. Ortiz-Veles, Jacob L. Perry, Michael W. Pennington, and Joseph M. Heiser. The authors are affiliated with Baylor College of Medicine, Pana Bio, Inc. or Ambiopharm Inc.

This project was funded in part by a pilot grant from the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine and by milestone funding from Baylor College of Medicine. The work was also supported in part by the Texas Institute for Cancer Prevention and Research (RP180672, RP150578, RP1806721, and RP170719), the National Institutes of Health (DK56338, CA125123, HG006348, and RR024574), the Dan L. Duncan Comprehensive Cancer Center, and the John S. Dunn Chemical Genomics Consortium coast of the Gulf of Mexico.

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Note. Materials provided above by Baylor College of Medicine. Content can be edited for style and length.

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