Our research and drug development work

How ulcerative colitis occurs:
What we know so far

Ulcerative colitis (UC) is generally thought to be a disease caused by a reaction of the immune system against some of its own proteins. The autoantibodies produced by the reaction of the immune system mistakenly attack the large intestine.
However, although many researchers have tried to find the proteins responsible for producing these autoantibodies, none have been successful so far.

It has been reported that autoantibodies attack and cause damage to colonic epithelial cells, but it remains unclear which proteins the autoantibodies are directed against.

What our research
team has discovered

Discovery of novel autoantibodies in ulcerative colitis

(1) After many years of research, in 2020 our research team discovered that ulcerative colitis patients have autoantibodies against a protein called integrin αVβ6 (anti-integrin αVβ6 autoantibodies). It was discovered that more than 90% of ulcerative colitis patients have this autoantibody, whereas it is rarely present in people who do not have ulcerative colitis.

This anti-integrin αVβ6 autoantibody inhibits the binding of integrin αVβ6 and fibronectin

(2) We discovered that this autoantibody (anti-integrin αVβ6 autoantibody) inhibits the binding of integrin αVβ6 (a substance that connects colonic epithelial cells together) to a protein called fibronectin.

Correlation between antibody titer and inhibitory effect

(3) We also found that the stronger the power of the autoantibodies, the stronger the inhibitory effect.

Pathophysiology hypothesis of ulcerative colitis from the perspective of these research findings

The autoantibody we recently discovered, anti-integrin αVβ6 autoantibody, inhibits the binding of integrin αVβ6, a protein in the colonic epithelium, to fibronectin, a substance that functions like “scaffolding.” This failure to bind causes colonic epithelial cells to peel off and form ulcers. This may well be how ulcerative colitis develops.

Summary of the research findings of our research team so far

Our research team considers “anti-integrin αVβ6 antibody” to be the causative autoantibody behind ulcerative colitis and is now pursuing further research along this line of inquiry.

Development of a measurement diagnostic kit

We believe that the measurement of anti-integrin αVβ6 autoantibody could be a valuable way to accurately diagnose ulcerative colitis (UC) and to assess the condition of the disease, thereby enabling better medical treatment for UC patients. Therefore, with the cooperation of Medical & Biological Laboratories Co., Ltd. (MBL), a leading Japanese manufacturer of antibody diagnostic agents, and the support of the Japan Agency for Medical Research and Development’s (AMED) “Advanced Research and Development Programs for Medical Innovation,” we have developed a measurement diagnostic kit.
Firstly, this means that by the end of 2021 hospitals throughout Japan will be able to perform measurements of the research reagent “anti-integrin αVβ6 autoantibody.” We expect to obtain regulatory approval for the kit from the Ministry of Health, Labour and Welfare by 2023, followed by insurance coverage and widespread adoption by 2025.

Our goal of developing a cure for ulcerative colitis

Our research team is also currently working to develop a new therapeutic drug aimed at curing ulcerative colitis. More specifically, we are aiming to create “a drug that eliminates only cells that produce anti-integrin αVβ6 autoantibodies.”

We are developing a drug that eliminates only B cells that express anti-integrin αVβ6 autoantibodies.
Since ulcerative colitis is caused by anti-integrin αVβ6 autoantibodies, such a drug will make it possible to cure the disease.

Request for support

If the findings of our research so far are correct and we are able to develop a therapeutic drug, we may just be able to find a cure for this “intractable disease” called ulcerative colitis.
We are highly motivated to develop a drug to cure UC as soon as possible.
However, drug research and development requires enormous amounts of labor, time, and money these days.
The aim of our research team is to complete R&D work on a candidate drug by 2025 and to commence clinical trials by 2026.
With a strong desire to develop a useful drug and relieve the pain of so many people as rapidly as possible, we have decided to issue a broad invitation for donations.
If you would like to support our efforts, your contribution will be warmly appreciated.

If you would like to donate toward the development of a therapeutic drug for ulcerative colitis, please click the button below.
Details about how to make a donation will be explained on the linked page.

To the donation page

Our research findings were published online in the international academic journal “Gastroenterology” on February 12, 2021.

文責

Masahiro Shiokawa, Takeshi Kuwada, Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
【glossary of technical terms】
Autoantibody
Antibodies are proteins that are made in the body to protect the body against bacteria. Autoantibodies are antibodies that react with the structures in your body.
Integrin αVβ6
It is a protein expressed in epithelial cells. It works to connect epithelial cells with surrounding tissues.
Fibronectin
It is one of the proteins that make up the tissue around epithelial cells.
The titer of autoantibodies
It represents the binding power of autoantibodies. In other words, the above figure shows that when the anti-integrin αVβ6 autoantibody becomes stronger, the action of inhibiting integrin αVβ6-fibronectin binding becomes stronger.
regulatory approval
In order to be recognized as a medical practice, it is necessary to obtain approval at a place called PMDA. This is called regulatory approval.
Insurance
Those that can bear medical expenses with health insurance. If you are not approved as an insurance medical treatment, it is called "not covered by insurance" and you will be treated at your own expense.
Basement membrane
It is the basis for fixing epithelial cells. It is composed of proteins such as collagen, fibronectin, and laminin.
力価
自己抗体の結合力を表します。つまり上図では抗インテグリンαVβ6自己抗体が強くなると、インテグリンαVβ6-フィブロネクチン結合を阻害する作用が強くなっていることを示しています。
Sensitivity
It is the probability that anti-integrin αVβ6 autoantibodies will be positive in patients with ulcerative colitis. Sensitivity of 90% or more like this time is considered to be a very good test.
Specificity
It is the probability that anti-integrin αVβ6 autoantibodies will be negative in patients other than those with ulcerative colitis and in healthy people. If it is 90% or more, it is a good test.