UA researchers are developing a new drug to treat inflammatory bowel disease — a condition of the gastrointestinal tract in which the body’s immune system attacks beneficial bacteria naturally found in the gut.
According to Eugene Mash, a professor of chemistry and biochemistry, the design of the new drug was inspired by Olestra, a common food additive that limits fat absorption, and is patent-pending under the wing of Tech Launch Arizona. UA researchers are optimistic that this drug can be an effective treatment for ulcerative colitis and colonic Crohn’s disease.
“Inflammatory bowel disease is a young person’s disease currently affecting at least 1.5 million people in the United States,” said Dr. Fayez Ghishan, head of the department of pediatrics and director of the UA Steele Children’s Research Center. “IBD can be either ulcerative colitis or Crohn’s disease, and is on the rise throughout the entire western world and in some underdeveloped countries.”
Ulcerative colitis is a disease that is limited to the colon, whereas Crohn’s disease can affect the entire gastrointestinal tract but is most commonly found near the end of the small intestine, explained Pawel Kiela, an associate professor of pediatrics and immunobiology.
“The sucrose core of the drug is linked to long chains of lipid-like molecules,” Mash said. “The compound essentially cannot be metabolized until it reaches the lower GI tract due to both its size and hydrophobicity. At that point, bacterial enzymes can reach the outsides of the molecule.” Then, the enzymes cut off 5-aminosalicylic acid molecules found on the ends of the drug.
Essentially, the drug resists getting activated until it reaches the place it is able to do the most good.
The molecule that gets cut off, 5-ASA, is commonly used to treat IBD. As the drug coats the mucus membrane of the GI tract, the 5-ASA molecules that are released suppress inflammatory mediators, Kiela explained.
According to Ghishan, current treatments for IBD are structured like a pyramid. Treatment starts with 5-ASA, but if patients don’t respond, it is followed by corticosteroids, immunosuppressive therapy and IV infusion of humanized antibodies.
The higher up in the pyramid the treatment is, the more the immune system will become suppressed and the more susceptible the patient will become to diseases like tuberculosis, hepatitis B and valley fever. The new drug is important because more patients will be able to stick with the 5-ASA treatment instead of going to more damaging treatments.
“Because our delivery vehicle for 5-aminosalicylic acid is not absorbed, you won’t have side effects,” Ghishan said. “That’s the beauty of non-absorbable drugs. We believe this is going to lead to a major advancement in our ability to treat young patients with ulcerative colitis.”
The newly developed drug is available in a liquid suspension rather than large capsules, so children will no longer have to rely on enemas, suppositories or expensive alternatives to treat their IBD.
In the current state, the limited market of the drug for IBD may not elicit interest in commercialization.
“My plea to pharmaceutical companies is to realize that our children are our future, and we need to find ways to improve their lives, irrespective of profit,” Ghishan said. “I am going to continue to fight to improve the lives of our children. That is a worthwhile goal.”
_______________
Follow Jacob Witt on Twitter.
