BioWorld International Correspondent

Amsterdam Molecular Therapeutics BV received a €1.8 million grant from the Dutch Ministry of Economic Affairs to advance the preclinical development of its interleukin-10-based ex vivo gene therapy for treatment of Crohn's disease.

AMT has developed proprietary technology - details of which remain undisclosed - that causes regulatory T lymphocytes that have been transduced to express the IL-10 gene to migrate specifically to the gut. The company, which is wholly owned by the Academic Medical Center (AMC), University of Amsterdam, already has conducted animal studies based on the approach. In a murine model of colitis, it demonstrated survival and long-term maintenance of body weight, primary parameters for suppression of inflammation in the gut. Moreover, the company said, local expression of IL-10 - an anti-inflammatory cytokine - does not appear to affect systemic immune responses.

Those studies, said Eric van der Aa, vice president of business development, were conducted using a retroviral vector optimized for expression in a murine background. The next step for AMT will be to obtain proof of principle in animals with a vector designed for human use. The company has not yet disclosed its target date for commencing human clinical trials, however.

The therapy, which was developed by one of AMT's founders, Sander Van Deventer, professor of gastroenterology at the AMC, is intended to provide long-term maintenance relief to Crohn's patients who relapse after conventional therapy.

"Right now, it's the failures on Remicade, for instance. And that's a very large population," van der Aa said, referring to the anti-tumor necrosis factor alpha monoclonal antibody marketed by Schering-Plough Corp., of Kenilworth, N.J., and Centocor Inc., of Malvern, Pa. AMT licensed rights to use IL-10 from Schering-Plough last year.

The company has two other gene therapy initiatives under way. Its lead program, which received €1.9 million in Dutch government funding, is focused on correcting lipoprotein lipase deficiency, a metabolic disorder that can lead to chronic pancreatitis and, eventually, diabetes mellitus.

"We are right into that, and we anticipate starting clinical trials in 2004," van der Aa said. AMT in-licensed that program from Xenon Genetics Inc., of Vancouver, British Columbia. Its third program, focused on gene therapy for familial hypercholesterolemia, was in-licensed from the Wisconsin Alumni Research Foundation, of Madison, Wis. That is still at the research stage, van der Aa said.

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