IBD: The Accidental Discovery to Treat


BALTIMORE, Md. (Ivanhoe Newswire) – It has been found that inhibition of this brain enzyme can be therapeutic in animal models of stroke, epilepsy, neuropathic pain and Lou Gehrig’s disease. Unfortunately, these drugs have poor penetration into the brain, which has hampered their clinical development. Now, there is new hope after that same brain enzyme was found in the gut during IBD flareups, opening the door to tackle neuro and gut disease through a simple pill.

For years, scientists have worked on drugs to inhibit a dangerous enzyme in the brain, called GCP2, which is increased in strokes and neurological dysfunction.

Barbara Slusher, PhD, Professor & Director at Johns Hopkins Drug Discovery explains, “The problem has been that we’ve developed all these drugs that don’t really get to the brain very well. It’s hard to get drugs across the brain blood barrier.”

(Read Full Interview)

Decades of research produced drugs to target the enzyme, but no way to actually deliver them to the brain.

“But about that same time, there was a group of scientists working in gastroenterology that found that this same enzyme, that we had been studying in the brain, goes way up if you have inflammatory bowel disease,” further explains Professor Slusher.

The neuroteam realized the drugs didn’t penetrate the brain, but would likely work in the gut – good news because the existing IBD drugs don’t help 30 percent of the patients.

Professor Slusher says, “We gave them to animals that had an IBD syndrome, and we found that their symptoms got better.”

And this opened the door to inhibiting the GCP2 in the gut using oral medication.

“So, we took these potent drugs that we had made that we couldn’t get to the brain, we put them orally and they got to the gut,” adds Professor Slusher.

The drug has been proven to work in multiple animal models, so Professor Slusher and teams are in the process of establishing clinical trials and business formation — preparing to go to market.

Contributors to this news report include: Donna Parker, Producer; Kirk Manson, Videographer; Matt Goldschmidt, Editor.

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REPORT:        MB #5366 

BACKGROUND: Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions that affect the gastrointestinal (GI) tract. The two main types of IBD are Crohn’s disease and ulcerative colitis. While both conditions share some similarities, they also have distinct differences in terms of their location and characteristics within the GI tract. Crohn’s disease can affect any part of the digestive tract, from the mouth to the anus, although it most commonly involves the small intestine and the beginning of the large intestine (colon). Ulcerative colitis primarily affects the colon and rectum, causing inflammation and ulcers in the innermost lining of the colon (mucosa) and rectum. Inflammatory bowel disease affects three million Americans, according to the CDC.

(Sources: https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/symptoms-causes/syc-20353315


DIAGNOSING: Symptoms of Crohn’s disease may include abdominal pain, diarrhea (which may be bloody), weight loss, fatigue, fever, and malnutrition. Common symptoms of ulcerative colitis include bloody diarrhea, abdominal pain or cramping, urgency to have bowel movements, and rectal bleeding. Diagnosis of IBD typically involves a combination of medical history, physical examination, laboratory tests (such as blood tests and stool tests), imaging studies (such as endoscopy, colonoscopy, or imaging scans), and sometimes biopsy of intestinal tissue. Differential diagnosis may be necessary to distinguish between Crohn’s disease and ulcerative colitis, as their clinical features and patterns of inflammation can overlap.

(Sources: https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/symptoms-causes/syc-20353315


NEW TECHNOLOGY: Researchers at Johns Hopkins are currently studying an enzyme that may treat patients with inflammatory bowel disease, or IBD. “The researchers synthesized several compounds containing common secondary bile acids and compared their effects in a mouse model of acute colitis. They found that an orally administered conjugate of 2-PMPA and deoxycholic acid called (S)-IBD3540 was superior to the other compounds in reducing disease activity. They confirmed that (S)-IBD3540 was restricted to the gut in healthy and colitic mice and that it was effective in reducing inflammation and disease severity. In patient-derived colon epithelial cells, the researchers found that (S)-IBD3540 protected against oxidative stress injury. Collectively, the results justify continuing to develop (S)-IBD3540 as a drug for IBD, the researchers determined.”

(Source: https://consultqd.clevelandclinic.org/researchers-identify-promising-compound-for-ibd-treatment#:~:text=A%20team%20of%20researchers%20from,inflammatory%20bowel%20disease%20(IBD).)


Caslon Hatch


If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

Doctor Q and A

Read the entire Doctor Q&A for Barbara Slusher, PhD, Professor of Neurology, Pharmacology, Neuroscience, Psychiatry, Medicine, and Oncology

Read the entire Q&A