Ulcerative colitis - On the horizon

Take a closer look at some of the promising areas of research and development for ulcerative colitis.

Stem cells

What are they?

Scientists believe stem cells, which have the ability to become any type of cellThe basic unit of all living organisms. in the body, may provide treatments and even a cure for inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis..

How does it work?

Stem cells could be used as a self-repair kit for the body. The hope is to repair the damaged bowel.

What stage of development has it reached?

Scientists have begun work in animals and have shown that stem cells taken from the bone marrowTissue within the bones where blood cells are formed. appear to protect the tissue from autoimmuneAny condition caused by the body’s immune response against its own tissues. attack. Many more safety studies are needed before the same approach is routinely used in patients. Trials have begun on patients with inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis. and have yielded very promising results.

Meanwhile, scientists at The University of Nottingham in England are investigating whether stem cellThe basic unit of all living organisms. markers could have a role to play in speeding up wound healing in patients suffering from inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. In the future, it may be possible to use therapies to manipulate the expression of these markers attached to the cells to promote even more rapid healing.

Genes and gene therapy

What is it?

There is strong evidence that geneticRelating to the genes, the basic units of genetic material. factors play an important role in determining susceptibility to inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis..

What is the aim?

Scientists hope that if they can pinpoint the genes responsible they will be better able to identify and treat ulcerative colitis and even cure people of the condition using geneThe basic unit of genetic material carried on chromosomes. therapy.

How does it work?

Gene therapy corrects the faulty genes that cause disease.

What stage of development has it reached?

Researchers have identified numerous genes that appear to be linked to Crohn's disease, but they have been slower discovering those for ulcerative colitis. German scientists recently found changes in three genes - PTPN2, HERC2 and STAT3 - unique to ulcerative colitis.  These genes encode for compounds in the body, called interleukins, which regulate inflammationThe body’s response to injury..

New drugs

What is it?

Investigators are searching for new medicines  to treat ulcerative colitis.

What is the aim?

To treat the symptoms and maintain disease remission.

What stage of development has it reached?

Emerging novel therapies include biological therapiesA group of therapies that interfere with specific parts of the inflammation process. (Called 'biologic therapies' in American English.) that use or mimic natural body substances to stop the inflammationThe body’s response to injury.. Examples include monoclonal antibodyOne of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. drugs like infliximab, selective adhesion molecule blockers like alicaforsen and anti-inflammatoryAny drug that suppresses inflammation cytokines like interleukin. Scientists are also studying the potential of growth factors to aid healing of the bowel lining. And UK scientists believe patients with inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis. may benefit from cannabis-based drugs.

Investigators are also exploring whether drugs used to treat other conditions might also treat inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. A drug used to treat rheumatoid arthritisInflammation of one or more joints of the body., called abatacept, is in late stage clinical trials for ulcerative colitis. Similarly, a drug for multiple sclerosis called interferonA substance that can inhibit viral growth. beta-1a is undergoing tests in patients with ulcerative colitis.

Nutritional and complementary treatments

What is it?

Conventional medicines and surgery - those your doctor would normally use - can control ulcerative colitis in most instances, but may cause side effects. For some, these adverse effectsUndesirable side-effects of medication. are so unpleasant that they may want to try non-orthodox treatments.

Who is it for?

Any patient who wants to try a therapy in addition to conventional treatments.

What stage of development has it reached?

There are many different alternatives being explored. Clinical trials are underway to evaluate aloe vera gel enemas in mild to moderately active distal ulcerative colitis.Scientists have also been testing a treatment based on pig whipworm eggs, based on the theory that our immune systems have evolved to cope with the presence of such parasites, and can become overactive without them.

Researchers in China believe retinoic acid, a form of vitamin A, could treat IBDAn abbreviation for inflammatory bowel disease, a group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. It may help to treat the inflammationThe body’s response to injury. associated with IBDAn abbreviation for inflammatory bowel disease, a group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. There is some research that suggests synbiotics may offer relief to people with inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. These contain live microorganismsOrganisms that are too small to be seen with the naked eye, such as bacteria and viruses. or "good bacteriaA group of organisms too small to be seen with the naked eye, which are usually made up of just a single cell." that will grow in the gut.

Research groups have been assessing an experimental treatment, called leukocyte apheresis , which uses a device to remove white bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. cells involved in the inflammationThe body’s response to injury. from the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. - the theory being that this will minimise inflammationThe body’s response to injury. and provide relief.

Risk factors/triggers

What is it?

Certain factors appear to increase an individual's chance of developing ulcerative colitis. Experts already know the disease tends to run in families, and seems to be at least be partly down to inherited genes. But they believe something in the environment probably triggers the disease in those who are susceptible.

What is the aim?

Scientists are continually looking for more risk factors and triggers so they can more accurately diagnose, treat and prevent ulcerative colitis.

What stage of development has it reached?

Some experts believe psychological stressRelating to injury or concern. can trigger ulcerative colitis and are testing this theory. Researchers suspect that nerveBundle of fibres that carries information in the form of electrical impulses. connections between the brain and the gut may stimulate inflammatory cells in the gut wall, which, in turn, enables potentially harmful bacteriaA group of organisms too small to be seen with the naked eye, which are usually made up of just a single cell..

Other recent work has looked at a protein called GLI1, which is involved in the development of the gastrointestinal tractThe gut, which begins at the mouth and ends at the anus. in the foetus. Errors in this protein may be linked with the later development of inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis..

Disease surrogate markers

What is it?

A surrogate marker is something that can be readily measured to give an accurate picture of how the disease is progressing.

What is the aim?

The aim is to find a measure that is quick, cheap and easy to monitor and that is a direct reflection of ulcerative colitis severity. This would allow doctors to monitor the treatments they give to see if they are really working and spot when they need to further intervene further.

What stage of development has it reached?

Scientists have identified a marker that is present in faeces, providing the possibility of a non-invasiveAny test or technique that does not involve penetration of the skin. The term 'non-invasive' may also describe tumours that do not invade surrounding tissues. test. Levels of this marker, called faecal S100A12, are increased if there is significant bowel inflammationThe body’s response to injury.. Similarly, faecal calprotectin has been proposed as a marker of inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. Another potential marker found in the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. is CXCL16.

Diagnostics

What is it?

Despite advances in radiological imaging and endoscopyExamination of the inside of the body using a tube equipped with a light source and either a small camera or an optical system., it can still be difficult to diagnose inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.. Accurate and early diagnosisThe process of determining which condition a patient may have. is essential, not least because the treatment and prognosis of ulcerative colitis and Crohn's disease differ.

What is the aim?

Experts are looking at ways to improve existing diagnostic methods, such as endoscopyExamination of the inside of the body using a tube equipped with a light source and either a small camera or an optical system. and magnetic resonance imagingA technique for imaging the body that uses electromagnetic waves and a strong magnetic field., and to find new tools, such as early disease markers in the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid..

What stage of development has it reached?

Scientists are finding more and more targets in the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. that could be used to flag up if someone is showing early signs of the disease.

On the horizon are several techniques involving CTA scan that generates a series of cross-sectional X-ray images. (computerised tomographyA scan that generates a series of cross-sectional X-ray images.) and MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field. (magnetic resonance imagingA technique for imaging the body that uses electromagnetic waves and a strong magnetic field.) scans, potentially in combination with PET imaging, that aim to improve these scans' diagnostic potential.

Detecting cancers - biomarkers

What is it?

Patients with ulcerative colitis have an increased risk of colonThe large intestine. cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. and for this reason scientists are looking for ways to spot those patients at the greatest risk and monitor them for the earliest possible signs of cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body., to enable treatment before the cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. progresses.

What is the aim?

Currently, detection of early cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. in ulcerative colitis patients involves repeated colonoscopies, where a camera is inserted into the bowel. But these are often incomplete and inaccurate. Scientists are hunting for biomarkersA substance that can be measured to help healthcare professionals to assess normal processes, disease processes or a person's response to treatment. - substances in the body that can be measured easily in the lab - that are highly predictive of cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. .

How does it work?

People with ulcerative colitis could be screened for the biomarker and those found to possess it could be monitored more closely and undergo treatment for any early signs of cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..

What stage of development has it reached?

Numerous research teams are searching for geneticRelating to the genes, the basic units of genetic material. biomarkersA substance that can be measured to help healthcare professionals to assess normal processes, disease processes or a person's response to treatment. to improve cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. surveillance. Others are looking for immunologic markers, such as antibodiesSpecial proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. against certain proteins found in cancerousMalignant, a tumour that may invade surrounding tissues or spread to distant parts of the body. and precancerous cells.

Minimising drug side effects

What is it?

Although the drugs used to treat inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis. are usually effective, not all people respond to them and some people may find them difficult to take because of side effects.

What is the aim?

Scientists are looking at ways to work out which patients are most likely to benefit from which drugs, in order to target existing treatments to those people most likely to respond and so avoid the risk of unnecessary side effects.

What stage of development has it reached?

Scientists have been focusing their efforts on the most commonly used immunosuppressantA drug that suppresses the immune system, reducing the body’s resistance to infection. drugs in inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis., azathioprine and 6-mercaptopurine (6-MP). They have been looking at monitoring the active end-products of these drugs, called thiopurines called thiogaunine nucleotides or TGNs.6 Experts believe they can measure TGNs in the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. to predict which patients are unlikely to respond to these drugs so that they can change over to another type of treatment as soon as possible.

Improving existing treatment regimes

What is it?

Experts are looking at new ways to use existing therapies, including new formulations with altered delivery and new dosing regimens.

What is the aim?

Either to reduce the unpleasant side effects that can cause patients to discontinue their treatment or to make particular treatments more effective.

What stage of development has it reached?

One group of scientists is developing an "intelligent pill" that could enable some of the more powerful IBDAn abbreviation for inflammatory bowel disease, a group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis. drugs to be delivered direct to the affected area of the bowel in order to limit side effects.7 Similarly, new 'colonic release corticosteroid formulations' may help to limit steroid toxicity.

Scientists are also investigating whether basiliximab, a drug that blocks a cellThe basic unit of all living organisms. receptor called IL-2, might reduce steroid resistanceThe ability of a microbe, such as a type of bacteria, to resist the effects of antibiotics or other drugs.. Steroid resistanceThe ability of a microbe, such as a type of bacteria, to resist the effects of antibiotics or other drugs. remains a major problem in ulcerative colitis with up to 30 per cent of patients failing to respond adequately to steroid therapy even at high dose and many progressing to colectomyThe surgical removal of the colon..

New surgical techniques

What is the aim?

Although ulcerative colitis can be treated with medications, some patients ultimately need the whole of their diseased large bowel removed to relieve their symptoms and negate any future risk of developing colonThe large intestine. cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.. Surgeons are looking at ways to do this surgery with the least trauma for the patient and the best outcomes in terms of quality of life.

How does it work?

In the past, surgeons used to perform an ileostomySurgery that involves bringing part of the small intestine, the ileum, through the abdominal wall. The intestinal contents are collected by a bag worn over the hole, or stoma., which entailed removing the colonThe large intestine. and attaching the small intestineThe section of gut, or gastrointestinal tract, from the stomach to the anus. to a small opening in the abdominal wall - called a stoma. An external pouch was then placed over the opening to collect waste. Now surgeons tend to do a proctocolectomy Surgical removal of the rectum and colon. - remove the colonThe large intestine. and attach the end of the small intestineThe section of gut, or gastrointestinal tract, from the stomach to the anus. to the anusThe external opening of the back passage, the rectum.. A pouch or reservoir is then created from the small intestineThe section of gut, or gastrointestinal tract, from the stomach to the anus. to replace the colonThe large intestine., allowing you to have bowel movements as usual.

What stage of development has it reached?

Surgeons are increasingly trying to do these operations laparoscopically - using "keyhole" surgery rather than traditional open surgery.

References: 
  1. Younghun J, Song J, Shiozawa Y, et al. 'Hematopoietic stem cells regulate mesenchymal stromal cellThe basic unit of all living organisms. induction into osteoblasts thereby participating in the formation of the stem cellThe basic unit of all living organisms. niche.' Stem Cells. 2008; 26(8): 2042-51.
  2. 'Astic trial'. University of Nottingham. Link
  3. Bai A, Lu N, Guo Y, et al. 'All-trans retinoic acid down-regulates inflammatory responses by shifting the treg/th17 profile in human ulcerative and murine colitis.' Journal of Leukocyte Biology. 2009; 86: 959-69.
  4. Kaiser T, Langhorst J, Wittkowski H, et al. 'Fecal S100A12 as non-invasiveAny test or technique that does not involve penetration of the skin. The term 'non-invasive' may also describe tumours that do not invade surrounding tissues. marker distinguishing inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis. from irritable bowel syndrome.' Gut. 2007; 56: 1706-13.
  5. Tillack C, Seibold F, Stark R, et al. 'Cxcl16 is a surrogate marker of inflammatory bowel diseaseA group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis..' Scand J Gastroenterol. 2008; 43(3): 283-8.
  6. 'The difficult problem of oral Crohn's disease: A unique pathological entity in IBDAn abbreviation for inflammatory bowel disease, a group of inflammatory conditions of the intestine. The two major forms are Crohn’s disease and ulcerative colitis.? '. National Association for Colitis and Crohn's Disease (NACC). Link
  7. 'Philips develops "Intelligent pill"'. Reuters. Link
  8. Medical News Today. 'Cerimon pharmaceuticals initiates arrest UC-1, a global phase 2b study of basiliximab in patients with steroid-refractory ulcerative colitis.' April 5 2007. Link