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IL-2 antibodies as an effective treatment of ulcerative colitis Intestinal
inflammation can occur in a number of pathologies, perhaps the most serious of
which is inflammatory bowel disease (IBD). IBD is an umbrella term used to
describe two distinct clinical conditions, ulcerative colitis and Crohn's
disease, both of which are chronic digestive diseases resulting from an
abnormal immune system response to stimuli in the digestive tract. In 2001, the
number of prevalent cases of IBD was been estimated to have totaled over 1.5
million in the major pharmaceutical markets. Currently in excess of $0.5
billion, IBD related sales have been forcasted to increase by 3-10% each year
for the next 5 years. Current treatment options are sub-optimal and the
present focus is on the identification of inflammatory mediators involved in
IBD. A greater understanding of inflammatory pathways and new "biologic
agents" that will emerge from this knowledge will expand the IBD market
and provide improved options for the patient. One treatment
option for ulcerative colitis is cyclosporine that acts by inhibiting
interleukin-2 (IL-2) production. A more direct approach is the use of IL-2
receptor blockers. A number of IL-2 receptor antibodies have been developed
including Novartis’ basiliximab and Biotest’s inolimomab; the former has
been launched while the latter is in phase III trial for the prevention of
transplant rejection. To our knowledge IL-2 receptor antibodies have yet to
enter clinical evaluation for the treatment of IBD. University of
Leuven researchers have therefore recently addressed this issue by conducting
a pilot trial to determine the efficacy and safety of a third humanized
anti-IL2 antibodies daclizumab in ulcerative colitis patients. This antibody
was first launched in 1997 by Roche for the prevention of transplant
rejection. Leuven researchers have now published data from an open label pilot
study of refractory ulcerative colitis. Ten patients with chronically active
ulcerative colitis were treated twice over a period of 8 weeks with 1 mg/kg
daclizumab. This protocol decreased clinical activity by over 50%. Likewise,
endoscopic scores were also significantly decreased at wk 8 while quality of
life was improved. This pilot study prompts the design of larger scale
clinical evaluations of daclizumab and other IL-2 receptor antibodies. Adapted from Van Assche et al, Am J Gastroenterol 2003 Feb;98(2):369-76 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.
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