LSI’s Innovation Partnership targets deadly diseases through novel initiative

March 31, 2009
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ANN ARBOR—Cancer, diabetes, strep infections and neurodegenerative diseases such as Alzheimer?s are the first targets of a novel University of Michigan program to shepherd promising biomedical discoveries from Life Sciences Institute labs to the marketplace.

The LSI Innovation Partnership uses philanthropic gifts to bridge the critical funding gap?known to biomedical researchers and venture capitalists as the Valley of Death ? between laboratory discovery and commercialization.

The program was launched last year with the goal of raising $10 million to support LSI discoveries. To date, donors have pledged about $2 million.

Four projects were recently selected for first-round funding totaling $680,000.

“The partnership brings to our faculty both the funds and the tool kit to take innovative, collaborative studies to the next level,” said Alan Saltiel, the Mary Sue Coleman Director of the Life Sciences Institute. “The projects are already off to a fast start, especially with the assistance of our external business partners.”

The Innovation Partnership is charting a new course toward commercialization, and it’s doing so in several ways.

One is its reliance on philanthropic organizations and individual donors to bridge the funding gap. Another is its adoption of a team approach that uses industry mentors and other experts to help guide LSI researchers as they usher their discoveries toward the marketplace.

In the Innovation Partnership program, each funded team is paired with mentors who are nationally renowned science/business executives and venture capitalists. They include Dr. James Niedel, managing director of New Leaf Venture Partners, a healthcare venture-investing firm.

“Although there are plenty of breakthroughs coming out of university biology programs across the country, there isn?t enough money to fund all the good ones,” Niedel said.

“The Innovation Partnership is a way of bridging that gap,” said Niedel, former chief science and technology officer at GlaxoSmithKline pharmaceutical.

The other Innovation Partnership mentors are Dr. Jeffrey Leiden, a partner at Clarus Ventures; Frank McCormick, director of the Comprehensive Cancer Center & Cancer Research Institute at the University of California, San Francisco; Craig Parker, a senior vice president at Proteolix Inc.; and David Walt, a Tufts University chemistry professor and co-founder of Illumina Inc.

In addition to the mentors, the four newly funded LSI teams have hired research scientists with industrial experience and have contracted with scientists outside academia. The U-M Office of Technology Transfer, the U-M Medicinal Chemistry program, and various biotechnology companies and pharmaceutical corporations will also provide guidance.

“This team approach will help LSI researchers avoid many of the pitfalls that can derail even the most promising projects before they reach the marketplace,” Saltiel said. “It is really extending our collaborative model to bring business know-how to these projects.”

The four first-round Innovation Partnership projects and their principal investigators are:

? “Developing novel inhibitors of metastasis,” Dr. Stephen Weiss.

One-year award: $250,000.

In solid tumors, the hallmark of malignancy is the tumor?s ability to penetrate a barrier layer known as the basement membrane, thereby gaining access to blood vessels that carry cancer cells throughout the body.

Weiss and his colleagues have found that tumor cells use three enzymes that act as “molecular scissors” to cut through the basement membrane. Their goal is to develop inhibitors to disrupt these enzymes and ? within two years ? to determine the value of using selected enzyme inhibitors as the basis for a spin-off company.

Weiss is a research professor at LSI, the Upjohn Professor of Medicine and Oncology, and Chief of Molecular Medicine and Genetics at the U-M Medical School.

? “Heat shock Protein 70 as a target for neurodegenerative disease,” Jason Gestwicki.

One-year award: $100,000.

Neurodegenerative diseases, such as Alzheimer’s and Huntington’s, arise from misfolded proteins that damage brain cells and trigger a progressive decline in cognitive abilities and motor function.

Gestwicki and his colleagues found that targeting a protein called Hsp70 protects against protein misfolding in cellular and animal models of neurodegenerative disease.

Funding from the Innovation Partnership will allow the team to develop and improve chemicals that eliminate misfolded proteins. Within two years, they hope to create the first class of drug-like molecules that directly targets the underlying cause of neurodegenerative diseases.

Gestwicki is a research assistant professor at LSI and an assistant professor of pathology at the U-M Medical School.

? ?Development of protein kinase inhibitors for the treatment of metabolic diseases,? Dr. Alan Saltiel.

One-year award: $150,000.

Obesity is associated with a state of chronic, low-grade inflammation that leads to insulin resistance, usually the first step in the development of Type 2 diabetes.

The Saltiel laboratory has discovered a protein kinase in an integral part of this inflammatory process. With funding from the Innovation Partnership, the team will attempt to develop inhibitors of the enzyme activity that reverse the obesity, chronic inflammation and insulin resistance associated with states of over-nutrition.

Within two years, the researchers hope to generate potent and specific small-molecule protein kinase inhibitors for further drug development.

Saltiel is the Mary Sue Coleman Director of the Life Sciences Institute and the John Jacob Abel Collegiate Professor in the Life Sciences and Internal Medicine.

? “Small compound inhibitors of streptokinase expression as a novel therapeutic approach to Group A strep infections,” Dr. David Ginsburg.

One-year award: $180,000.

Group A streptococci bacteria cause 700 million infections worldwide each year, including more than 500,000 deaths. The bacteria invade human tissues in part by dissolving protective blood clots.

The Ginsburg laboratory has identified several compounds that block the bacteria’s ability to dissolve blood clots, thereby preventing the infection from spreading. With funding from the Innovation Partnership, the team will attempt to identify additional compounds, then optimize the best candidates and test them on mice.

Within two years, the team hopes to have candidate compounds ready for testing in large animals such as horses (which suffer from a similar infection), with an eye toward eventual human trials.

Ginsburg is a Howard Hughes Medical Institute Investigator, the James V. Neel Distinguished University Professor of Internal Medicine and Human Genetics, a research professor at the Life Sciences Institute, and the Warner-Lambert/Parke-Davis Professor of Medicine.

The Innovation Partnership is designed to bridge the Valley of Death, the funding gap that arises after federal basic-science support ends and before investors are willing to commit to a promising discovery.

Projects are selected based on the strength of the science and the potential for commercialization. The Weiss and Ginsburg projects were chosen by a committee of internal and external experts; the Saltiel and Gestwicki projects were funded directly by a donor.

The U.S. National Institutes of Health funds much of the basic biomedical research at LSI and at universities across the country. And once researchers can reliably show that a discovery has immediate applications, commercial investors step in.

But finding the “gap funding” needed to establish a new discovery’s commercial viability can be a daunting challenge. Investors who once filled that void have reduced their support in recent years.