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Biotech firm uses live heart tissue in drug screens

Milwaukee, Wis. - InvivoSciences LLC, a startup biotechnology firm with laboratories in Milwaukee, is working to help drug developers bridge the gap between molecular and animal testing methods. For researchers studying heart diseases, skin disorders, and other maladies, Invivo's manufactured live tissue system could provide that bridge.

Using tissues derived from neonatal rats, the company - featured at a recent meeting of the Wisconsin Biotechnology and Medical Device Association - has created a screening system that allows researchers to test drug candidates on live tissue en masse.

A single rat, culled from colony surpluses, can provide five to 10 live tissue samples. Within two weeks of the initial preparation, the heart tissue "matures" and will continue contracting regularly like a beating heart for a month or longer.

The result is a high-throughput screening method that enables drug developers to screen between 2,000 and 3,000 samples per day.

Tetsuro Wakatsuki, chief scientist and co-founder of Invivo and assistant professor of physiology at the Medical College of Wisconsin, explained that the technology is advantageous because it eliminates cell-to-cell variability. It also minimizes unrelated and invalid leads and protein targets due to toxicity issues, for example, at very early stages of the drug-discovery process.
The information gleaned from the testing method also allows researchers to study biological responses in a three-dimensional environment instead of gathering data from chemical reactions or two-dimensional cell-based assays.

The heart tissue or blood vessel samples can be cultivated to suit large drug-screening projects on 96-well plates, and they can be assembled to provide models for specific disease conditions with either healthy, sick, or genetically modified tissue.

The technology has the ability to help scientists address a variety of diseases, including cardiac fibrosis, hypertension, and asthma, with additional applications in scar contracture, wound healing, and aging skin therapies.

"The ultimate goal is to discover new drugs," Wakatsuki said.

Big business

The Milwaukee-based start up launched in 2001 with capital from its three founders: Wakatsuki, company president Ayla Annac, and Elliot Elson. Washington University in St. Louis provided the license to its patented technology. To access the lucrative market for this technology, Invivo will need more capital soon.

Invivo straddles a few overlapping drug development markets, Annac explained. The U.S. cell analysis market was $5.1 billion in 2004, with 50 percent growth per year, and the therapeutic efficacy and toxicity testing markets comprise approximately $1.1 billion in the U.S., she said.

Annac said that she is aiming for a minimum first round angel investment of $250,000 in the near future. Securing adequate equity investment will allow Invivo to its launch its product within about six months.

In addition, Invivo has sought help from the federal government. The company submitted a new Small Business Technology Transfer (STTR) Phase I grant application in April 2006, and resubmitted a Phase II STTR grant application in August.

Strategic partnerships

Invivo's strategic partnerships have contributed significantly to the company along the way, and Annac is planning to extend the company's collaborative reach.

The Wisconsin Department of Commerce was "instrumental in nourishing the company," Annac said. The agency facilitated Invivo's search for drug-screening collaborators, grant writers, and space at its incubation center in Milwaukee.

"Wisconsin has been very friendly for us as a start up. It is an advantageous location for financing and staffing, and we have felt very welcome here," Annac said.

Additionally, with collaboration from the Medical College of Wisconsin, Wakatsuki has found all the advanced equipment and expertise he needed to advance into drug discovery.

The National Institutes of Health fund several contributing national MCW centers that have had formative roles in Invivo's growth including the Proteomics Center, the Human and Molecular Genetics Center, and Programs for Genomics Applications led by Andrew Green, Howard Jacobs, and Allen Cowley, respectively.

And to develop its instruments, Invivo collaborates with Gilson Inc., a liquid handling and in lab-automation provider.

"Gilson's expertise is playing a crucial role," Wakatsuki explained.

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