Investigators at the Case Western Reserve University School of
Medicine discovered that blocking interleukin-1α (IL1α), a protein that
controls inflammation in the gut, markedly decreases the severity of intestinal
inflammation in a mouse model of Crohn’s disease (CD).
The anti-inflammatory effects of the biological therapies used to
neutralize IL1α were similar to those of steroids, which represent what is
generally considered the gold standard of treatment for these patients. In
addition, the researchers found that the effect of anti-IL1α treatment was
controlled by changing the composition and function of the gut microbiome.
Their findings will be published online this week in the Proceedings of the National Academy of Sciences.
“This is one of the first studies, to our knowledge, that links
the effect of a specific cytokine, such as IL1, to the gut microbiome,” said
lead author Fabio Cominelli, professor
of medicine and pathology at Case Western Reserve University, and division
chief of gastroenterology at University Hospitals Cleveland Medical Center.
Furthermore, the study provides the preclinical rationale for
performing the first clinical trial blocking interleukin-1 in patients with
inflammatory bowel disease (IBD), which Cominelli and his collaborators at
Xbiotech Inc., a biosciences company based in Austin, Texas, who developed a
human monoclonal antibody against IL1α, are planning for the near future.
“I’m really excited about this study because I started my career
three decades ago collaborating with (co-author) Dr. Charles Dinarello, professor
of medicine at the University of Colorado, who discovered and cloned
interleukin-1 in the early ’80s,” Cominelli said. “Now I have the opportunity
to collaborate again with him in this exciting project that has the potential
to develop a novel biological therapy for patients with IBD.”
IBD, which refers to Crohn’s disease and ulcerative colitis, affects more than 3 million adults in the United States, according to the Centers for Disease Control and Prevention (CDC). This estimate does not include children who may also have IBD. Most people with IBD are diagnosed in their 20s and 30s, according to the CDC.
These ailments are chronic, relapsing, inflammatory conditions of
the gastrointestinal system characterized by severe pain, diarrhea, bleeding and
sometimes intestinal complications requiring surgery.
To date, there is no cure for these devastating diseases, and
available therapies are effective in only about half of IBD patients.
“Therefore, there is a great need for developing new biological therapies, such as anti-IL1 monoclonal antibodies,” Cominelli said.