Future administration of PNAS: pills instead of injections

For chronic diseases such as rheumatoid arthritis, treatment usually requires lifelong injections
.
Fear of needles, injection-related infections and pain is the reason patients skip doses, which encourages the development of new dosing strategies that combine efficacy with limited side effects to adequately treat patients
.

Researchers at Baylor College of Medicine and its partner institutions have explored a better way to deliver the drug that doesn't require an injection but can be as simple as
swallowing a pill.
The study was published in the Proceedings of the National Academy of
Sciences.

Dr.
Christine Beaton, professor of integrative physiology at Baylor University and co-corresponding author, said: "People don't like to be injected
all their lives.
" "In our current work, we explore the possibility
of using the probiotic Lactobacillus reuteri as a novel oral delivery platform in animal models to treat rheumatoid arthritis.
"

Previous studies by the Beaton lab have shown that a peptide or short protein extracted from seaweed toxin can effectively and safely reduce disease severity
in rat models of rheumatoid arthritis and in patients with plaque psoriasis.
"However, peptide treatment requires repeated injections, reducing patient compliance, and direct oral administration of peptides is less
effective," Beeton said.

Beaton and Professor of Molecular Virology and Microbiology, Belledan M.
Dr.
Robert A.
Britten, a member of the L.
Duncan Comprehensive Cancer Center, collaborated
.
Britten's lab has developed the tools and expertise
to genetically modify probiotics to produce and release compounds.
In the current study, the team bioengineered Reu's probiotics to secrete the peptide ShK-235
extracted from sea anemone toxin.

They chose Lactobacillus reuteri because these bacteria are native to
the guts of humans and other animals.
It is one of the lactic acid bacteria that has long been used by the food industry as a cell factory and is recognized as safe
by the U.
S.
Food and Drug Administration.
Lactobacillus reuteri has an excellent safety profile
in infants, children, adults, and even immunosuppressed people.

"The results are encouraging," Beaton said
.
"In animal models of rheumatoid arthritis, daily injections of these peptide-secreting bacteria, called LrS235, greatly reduced the clinical symptoms of the disease, including joint inflammation, cartilage destruction, and bone damage
.
"

The researchers tracked the bacterium LrS235 and its peptide ShK-235
, secreted in animal models.
They found that after feeding rats live LrS235 that released ShK-235, they could detect ShK-235 entering the blood circulation
.

"Another reason we chose Lactobacillus reuteri is that these bacteria don't stay in the
gut permanently.
As the gut regularly renews the inner surface layer to which bacteria attach, they are removed," Beaton said
.
"This opens up the possibility
of standardizing treatment management.
"

More research is needed to bring this new drug delivery system into the clinic, but the researchers anticipate that in the future it could make treatment easier for patients
.
"These bacteria can be stored in capsules, which can be placed on kitchen counters," Beaton said
.
"Patients can take capsules while on vacation without needing to refrigerate or carry needles, and can continue treatment without the need for daily injections
.
"

These findings provide an alternative delivery strategy for peptide-based drugs and suggest that this technique and principle can be applied to a wider range of drugs and the treatment
of chronic inflammatory diseases.