People with Crohn’s disease, an
immune disorder causing inflammation mainly in the intestines, have been forced
to learn how to manage and understand their “gut.”
This, together with the
chronicity of the disease and the pretty serious medications often required,
means sufferers are usually very open-minded about new approaches to relieve
debilitating symptoms. While the exact cause of Crohn’s is unknown, researchers
believe there is a link to the “hygiene hypothesis,” the notion that there is an increase in autoimmune disease
incidence rates related to clean, modern Western society.
The hygiene hypothesis states that ridding
our bodies of parasitic worms and beneficial bacteria has paved the way for higher
autoimmune disease rates - and that by reintroducing microbes into our bodies, we
can treat some of these patients. Doing this would, perhaps, help regulate the
immune system, increase the diversity of microflora and potentially shift the
pro-inflammatory state toward homeostasis. People without autoimmune diseases are
known to have a much more diverse microbiome than those with disease, and
certain markers of inflammation are increased in disease than without.
Trichuris
suis ova (TSO) - pig whipworm eggs - is the first application of the hygiene
hypothesis to be studied as an investigational treatment under FDA protocol. Studies have shown
that once TSO has been swallowed by a patient, the eggs take up residence in
the gut and regulate the immune system in a way that may reduce a range of
symptoms of Crohn’s and other diseases affecting the immune system. This natural
approach was chosen based on the hygiene hypothesis, and the specific agent, TSO,
is attractive since it is the pig whipworm and cannot
grow into worms and colonize in a human. In fact, if treatment is stopped,
within a very short period of time, the living organism can no longer be
detected in the body.
Credit: Reuters. Link: Fox.
The worms appear to produce three
major effects on the immune system: they seem to trigger changes that activate
and increase the number of regulatory T cells which dampen immune responses and
curb autoimmunity; they seem to act on other cells to prevent the “switching
on” of dangerous effector T cells, which customarily results in inflammation
and disease; and they seem to alter the makeup of intestinal flora—they foster
the growth of gut microorganisms customarily considered “probiotic,” which
assist in maintaining intestinal health.
At Coronado Biosciences, where I am Executive Vice President
of Scientific Affairs, we have been pursuing research using TSO, but it isn’t just research to me — I have a personal
interest too. At 16, I was a rising star on the international tennis circuit.
Playing for the Swedish National team, I was competing almost professionally. Then
Type 1 diabetes came calling, derailing my tennis career and changing the
course of my life. Today, armed with both M.D., and Ph.D. degrees, a strong background in business, a
new kidney from my father and a transplanted pancreas, I am diabetes-free and
determined to help others either cope with or avoid what I could not: the
unexplained onset and destructive power of autoimmune diseases.
I’m
proud, therefore, that Coronado Biosciences recently completed enrollment of our
Phase 2 study of TSO in Crohn’s disease. The trial, known as TRUST-I,
has enrolled 250 patients between the ages of 18 to 65 with moderately to
severely active Crohn’s.
The final number of patients surpassed the target
enrollment of 220 patients to accommodate individuals in the screening process
when the trial's enrollment goal was achieved. Patients enrolled into the study
are receiving either 7500 TSO or placebo once every two weeks, for 12 weeks,
followed by another 12 weeks of open-label treatment with TSO. We are
encouraged by the fact that many patients have elected to enter the open-label portion of the study.
Investigators are measuring the response rate
according to the Crohn’s Disease Activity Index (CDAI), an established and
well-accepted grading tool for clinical trials in this disease. We expect to
release results in the fourth quarter of 2013.
The
interest from the medical community to study TSO in a number of autoimmune
diseases has been impressive. Coronado has received and continues to receive
requests and proposals for clinical trials from leading clinicians and
researchers around the world. If additional studies prove promising, it could
portend a new era for patients of Crohn’s and other autoimmune diseases.
Karin Hehenberger,
M.D., Ph.D. is Executive Vice President of Scientific Affairs at Coronado
Biosciences, a biopharmaceutical company focused on the development of novel
immunotherapy biologic agents for the treatment of autoimmune diseases and
cancer.
