From genes to drugs for IBD

[Guest guest]

You may recall that a new gene determining susceptibility to

inflammatory bowel disease (IBD) was recently identified:

Duerr RH, KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ,

Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T,

Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT,

Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. A genome-

wide association study identifies IL23R as an inflammatory bowel

disease gene. Science. 2006 Dec 1;314(5804):1461-3. PMID: 17068223.

The above study suggests that effective treatment for IBD could come

from targeting interleukin-23 (IL-23). " These results and previous

studies on the proinflammatory role of IL-23 prioritize this

signaling pathway as a therapeutic target in inflammatory bowel

disease. "

IL-23 is known to be a driving force behind intestinal inflammation:

Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie

F, Maloy KJ. Interleukin-23 drives innate and T cell-mediated

intestinal inflammation. J Exp Med. 2006 Oct 30;203(11):2473-83.

PMID: 17030949.

So it's encouraging to see the following report, which suggests that

a drug that inhibits IL-23 may be of benefit in treatment of Crohn's

disease:

IDrugs. 2007 Jan;10(1):53-9.

Drug evaluation: Apilimod, an oral IL-12/IL-23 inhibitor for the

treatment of autoimmune diseases and common variable immunodeficiency.

Billich A.

Novartis Institutes for Biomedical Research, Brunner Strasse 59, A-

1235 Wien, Austria. andreas.billich@....

Apilimod is a small molecule that inhibits IL-12 and IL-23

production - cytokines that are involved in autoimmune diseases -

through the prevention of nuclear translocation of c-Rel. Synta

Pharmaceuticals Corp is developing apilimod for the potential

treatment of Crohn's disease (CD) and other autoimmune diseases.

Preclinical studies demonstrated the successful inhibition of IL-12

and IL-23 production by the drug. In the clinical setting, apilimod

has been generally well tolerated, with mild-to-moderate side effects

reported, including headaches and nausea. Patients with CD responded

within 14 days of treatment with apilimod and, after 28 days, the

drug significantly reduced the Crohn's disease activity index (CDAI).

Apilimod is currently in phase II clinical trials for rheumatoid

arthritis, common variable immunodeficiency and CD. From the data

available to date, apilimod appears to be a promising treatment for

CD, and the oral formulation of this compound provides an advantage

for apilimod over injectable therapies. PMID: 17187316.

A prediction would be that the patients best responding to this drug

might be those that carried the IL23R genetic variants associated

with susceptibility to IBD in the Duerr et al (2006) study, above?

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

[Guest guest]

,

Thanks for bringing a ray of hope from time to time.

Von