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INFLAMMATORY BOWEL DISEASE (IBD)
Clinical
Inflammatory bowel disease (IBD)
is a term used to cover a variety of disorders including
Ulcerative Colitis, Crohn’s
Disease and Non-specific colitis. A common feature is inflammation
of the gut resulting in pain and bloody diarrhoea. One
of the main differentiating factors between the diseases
is the location of the inflammation.
Crohn’s Disease is characterised
by relapsing / remitting inflammation across the entire
thickness of the
gut. It may affect any part of the gut. It affects 50 per
100,000 population, with 5 new cases/100,00/year in northern
Europe, USA and Australia. It is 4 times more common in
smokers. Upto 30% of patients have extra-intestinal manifestations,
such as eye inflammation and arthritis.
The mainstay of therapy is steroids. These are effective,
but side effects limit their chronic use. 5-asa derivatives
are of benefit for colonic disease, but have limited effect
on small bowel disease. Overall, 80% of patients need surgery
at some stage. Half of these are emergencies. There is
no cure, with a 10% relapse rate/year.
Double contrast Barium
enema of large bowel
Source: Public Health Image Library
Ulcerative Colitis is characterised by relapsing / remitting
inflammation of the mucosa of the large bowel. It affects
100 per 100,000 population, with 10 new cases/100,000/year.
It is twice as common in non-smokers. 10-20% have extra-intestinal
manifestations, usch as primary sclerosing cholangitis
and arthritis. Steroids are used for acute attacks, but
have no effect on relapse rate. All 5-aminosalicylic compounds
reduce relapse rate by about 4-fold, from 80% to 20% at
1 year. All have side effects. Overall the average patient
will have 1 relapse every 5 years, with 25% overall needing
surgery.
Non-specific colitis includes rare disorders such as microscopic
colitis, collagenous colitis, diversion colitis, ischaemic
colitis and pseudomembranous colitis.
There is a need for both more effective acute therapies,
to decrease the rate of emergency surgery, and for more
effective prophylactics. These are complex diseases, and
developing valid disease models is often problematic. None
fully recapitulate the human disease state fully and none
are amenable to a rapid functional and histological assessment
of bowel pathology.
DanioLabs approach
DanioLabs is identifying and developing
compounds to treat both the acute and chronic disease states,
and have developed
a high-throughput proprietary disease model which more
closely replicates the human disease state than others
that are available. In particular:
• Clinical Relevance : Resolution
with standard treatments (steroids, 5-ASA);
• Pathological Relevance: Characteristic changes such as
transdifferentiation, metaplasia and mast cell proliferation;
• Biological Relevance: TNF  upregulation; region specific
changes throughout gut through mechanisms similar to human
disease.
DanioLabs portfolio
Through a phenotypic approach to compound screening, rather
than one that focuses upon a single element of the disease,
DanioLabs is able to select drugs that rescue the phenotype, and
to reverse the disease state to normal, both functionally
and histologically, rather than just affecting a particular
biochemical parameter.
A variety of compounds which reverse phenotype have so
far been identified. DanioLabs will over the next 12-18 months
select the best candidates to progress through the development
process.
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