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Toronto Hospital Home PageKey Regulator of Intestinal Growth Hormone Discovered
Discovery Leads to Designer Hormone
which will Play a Critical
Role in Clinical Trials for Patients Suffering from Intestinal Diseases
June 23, 1997 ... Less than a year after discovering
the function of a hormone necessary for stimulating the growth of the lining
of the small intestines, researchers at The Toronto Hospital and Allelix
Biopharmaceuticals have developed a synthetic version which is 3-5 times
more powerful.
The analog of GLP-2, a naturally occurring peptide hormone, will set the
strategy for clinical trials that will likely lead to the development of
a drug therapy for thousands of people suffering from intestinal and/or
bowel diseases.
GLP-2 acts to stimulate the rate of growth of the lining of the small intestine,
increasing the absorption of nutrients. Several serious medical conditions
can interfere with the function of the epithelium (lining of the intestines),
including short bowel syndrome, Crohn's disease, ileitis and intestinal
inflammation. Currently, there are no effective therapies available for
enhancing the growth and repair of the small intestine epithelium.
"We have synthesized a new GLP-2 molecule which appears to be more
effective than the natural occurring hormone in promoting growth effects
in the intestinal lining," says Dr. Daniel Drucker of The Toronto Hospital
and the University of Toronto Banting and Best Diabetes Centre. "Our
work suggests that GLP-2 analogs could play a critical role to better treat
intestinal diseases in humans."
The development of the GLP-2 analog was made possible following the discovery
by Dr. Drucker and his research team that a key enzyme dipeptidyl peptidase
IV (DDP IV) regulates the biological activity of GLP-2.
These findings are published today in Nature Biotechnology.
The intestinal growth factor, GLP-2, is found in all animals but its relative
activity depends on the concentration of circulating intact GLP-2 protein.
This observation led the scientific team to discover that DDP-IV is the
enzyme that degrades and inactivates GLP-2.
The Allelix research team then went about designing a series of new, synthetic
GLP-2 analogs and tested their resistance to DDP-IV-mediated inactivation.
Several of the synthesized GLP-2 analogs were found to be resistant to degradation
by the enzyme. In addition, Dr. Drucker's team also found these analogs
to be a more powerful stimulator of intestinal growth than the naturally
occurring hormone.
"This finding is very exciting," Dr. Drucker says. "By identifying
the key regulator of GLP-2 activity, we've been able to produce an analog
which is 3 to 5 times more active than nature's own."
"Allelix intends to start clinical trials next year using one of the
GLP-2 analogs," Dr. Drucker says. "Based on our new results, a
more powerful GLP-2 analog may be the drug of choice."
The Toronto Hospital is Canada's largest acute care facility with approximately
1200 beds. It has gained an international reputation for excellence in patient
care, teaching and research in its four priority programs: cardiac sciences,
neurosciences, transplantation and oncology.
For more information contact, Josey Panetta,
Senior Media Relations Officer,
The Toronto Hospital, 416-340-3303