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Celiac disease drug that targets the immune system shows early promise

March 26, 2021

Treatment based on nanoparticles appears to prevent immune activation by gluten, study finds

By Amy Ratner, Director of Scientific Affairs

A new approach to treating celiac disease by using nanoparticles to program the immune system to tolerate gluten showed promise in early results, according to a newly published study.

The study concluded that the drug, TAK-101, prevented gluten from triggering an immune reaction in those who have celiac disease. The results, which were previously presented preliminarily at a European gastroenterology conference, were published in the journal Gastroenterology.

TAK-101 has been described as acting like Trojan horse in the way it carries a hidden component of gluten to reprogram the immune system not to react, as it incorrectly does in celiac disease.

Related: Early promise of nanoparticles reported

In the Phase 2 study, 33 study participants with celiac disease who had been on the gluten-free diet for at least six months and had no symptoms or positive antibody blood tests were divided into two groups. One group was pre-treated with TAK-101 by getting intravenous injections of the drug. The other group got injections of a placebo. Both groups then had a 14-day gluten challenge, during which they received 12 grams of gluten for three days followed by 6 grams of gluten for 11 days.

T-Cells: White blood cells that function as the body’s disease fighting soldiers and are improperly activated by gluten in those who have celiac disease


The effect of the nanoparticle treatment was evaluated by looking at pro-inflammatory cytokine interferon-gamma, which is a way of measuring how immune T-cells are responding to gluten. This T-cell response is the starting point of celiac disease. Study participants who were given the TAK-101 had 2.01 interferon-gamma spot forming units compared to 17.58 in the placebo group when tested on the sixth day of the gluten challenge.

Primary endpoint: The main result of a clinical trial that is measured at the end of a study to see if a given treatment worked


The T-cell response in the group that received the drug was reduced by nearly 90 percent, the study says. Measurement of the interferon gamma was the primary end point of the study.

Study authors noted that while TAK-101 prevented immune activation by gluten, there was no evidence that is caused broader suppression of the immune system.

Related: Celiac disease treatment could open doors for other autoimmune diseases

In the next phase of study, researchers will investigate the connection between a TAK-101 reduction in interferon gamma and the effect it has on symptoms in those who have celiac disease, said Daniel Leffler, MD, a study author and medical director of clinical science at Takeda Pharmaceutical Company. Takeda is developing TAK-101.

Investigators will also study how long treatment with TAK-101 lasts, an important step because the Phase 2 study covered a short period of time. Also, the Phase 2 study used high doses of gluten to stimulate the gluten response, so a “real world” clinical trial based on the amount of gluten typically consumed by celiac disease patients on a gluten-free diet is needed to determine if TAK-101 prevents symptoms and, over time, prevents intestinal damage.

Leffler noted that a treatment that prevents the T-cell reaction in celiac disease has not yet been developed so scientists are still making new discoveries. “This is something that is acknowledged as sort of the Holy Grail for celiac disease – if you could reset the immune system to turn off this abnormal reaction,” Leffler said. “I think this is the first tangible step towards a therapy that could reset the immune system and make someone not react to gluten.”

Intestinal damage

Although changes in biopsies were not a primary focus of the trial, researchers also measured and compared intestinal damage in both the study participants who received TAK-101 and those who were given a placebo.  Those in the placebo group had increased damage after the gluten challenge while those who received the drug did not, but a comparison of the change in biopsies between the two groups was not statistically significant, the study says.

The best thing researchers expected to see in biopsies in the group that got the drug was no additional intestinal damage, which was achieved, Leffler said.

Researchers also looked at multiple types of white blood cells and found that with TAK-101 treatment there was an overall reduction in the intestine of a number of types thought to be harmful in celiac disease. Meanwhile the drug did not affect white blood cells not related to celiac disease that can have a useful function, for example fighting infections. “We saw no changes where we didn’t want to see them and we saw differences where we were hoping to see them,” Leffler said.

Safety and tolerability

Phase 1 results also reported in the study concluded the drug was safe and well tolerated by study participants. Twenty three study participants were given various doses of the drug in that early phase clinical trial.

The study was done by scientists from Beth Israel Deaconess Medical Center, Harvard Medical School and the Mayo Clinic in addition to those from Cour Pharmaceuticals, Takeda  and Northwestern University. TAk-101 is being developed by Takeda, which provided funding for the study. Takeda took over development of the drug, which was developed by Cour, based on study results.

You can read more about the study here.


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