Case Western Reserve University Receives $5M from Third Frontier Commission for the Center for Stem Cell & Regenerative Medicine
Funding supports multiple commercial, emerging and pilot projects

CLEVELAND—The Center for Stem Cell & Regenerative Medicine (CSCRM), comprised of Case Western Reserve University (CWRU), Cleveland Clinic (CC), University Hospitals Case Medical Center (UHCMC), and Athersys, Inc. has received $5 million from Ohio’s Third Frontier Commission under the Research Commercialization Program. The funding will help support new and innovative stem cell technologies including two commercial, four emerging and three pilot projects.  This funding will be matched by each of the projects to create a $10 million grant benefiting stem cell are regenerative medicine research in Ohio.

“This funding provides CSCRM the support it needs to continue to aggressively move new technologies from academic labs towards commercial development,” said Stan Gerson, Director of the Center for Stem Cell & Regenerative Medicine. “We have linked corporate partners to our major projects and have been gratified by the development of a stem cell biotechnology commercial landscape in our region. Our goal is to rapidly move stem cell research from the lab to patients through clinical trials, using our strong background in preclinical models.”

The continued research efforts will result in efficient clinical applications and commercialization of stem cells to benefit patients throughout Ohio. To date, such efforts have brought in $170 million in new commercial development and investment in Ohio.

“This grant continues to build distinctive and broad reach capabilities that are making Ohio a leader in the development and clinical use of cellular therapies,” said Baiju R. Shah, President and CEO of BioEnterprise. “Ohioans benefit both through the resulting company development and jobs as well as by having access to leading-edge clinical therapies at our region's clinical institutions."

The use of stem cells has focused on leukemia and myeloma treatments with recent applications in cardiovascular disease.  Current healthcare is limited to the use of drugs or devices to treat disease and injury. CSCRM, located in Northeast Ohio but collaborating state wide, is uniquely positioned to rapidly implement new stem cell technologies in the commercial and therapeutic arenas.

“I can see stem cells replacing drugs to improve many diseases,” said Dr. Gerson. “Stem cells can replace injured cells, improve the function of many organs in the body and provide specific new functions to treat many diseases.”

The Third Frontier funding will support the following commercial, emerging and pilot programs:

Commercial programs
The commercial projects are expected to generate significant near term value for the sponsoring companies and the State of Ohio. 

The first commercial project involves Athersys and Kenneth Cooke (UHCMC and CWRU) to further evaluate MultiStem® to cure immunological reactions to cell related therapies for cancer. The goal of this project is to advance the commercialization of MultiStem® cell therapy by running a FDA approved Phase II clinical trial to evaluate the performance of the cells. Additionally, treatment of pulmonary complications during stem cell transplantation will be investigated to pursue the treatment of Acute Respiratory Distress Syndrome (ARDS). MultiStem® cells convey a survival advantage and enhance tissue regeneration (in the gut, lung, liver and immune system) in test animals that have been exposed to debilitating or otherwise lethal doses of irradiation. Thus, it is anticipated that administration of MultiStem cells to cancer patients recovering from radiation or chemotherapy will accelerate tissue regeneration and repair, and enhance patient recovery.

Juventas Therapeutics, located in Cleveland, is a spin out from CSCRM and CC by Marc Penn (CC) that has freedom-to-operate in multiple disease areas, has raised nearly $8 million in venture capital, and has moved from pre-clinical stage to Phase I clinical study with FDA approval of its investigational new drug (IND). Juventas will use ODOD funding and company dollars to develop its lead drug product, stromal cell derived factor 1 (SDF-1), through a Phase I clinical trial for critical limb ischemia (CLI). Localized SDF-1 delivery recruits circulating stem cells to the site of damaged tissue and results in angiogenesis, which is sustained for months after the SDF-1 signal is removed. The ability to restore blood flow to the legs of peripheral artery disease patients will significantly reduce pain and halt progression of tissue damage caused by prolonged ischemia. Within 3 years, Juventas will have human data demonstrating the safety and efficacy of SDF-1 in a large, underserved patient population and be poised to raise significant venture capital for additional clinical research required to bring the product to market. 

Emerging programs
With further refinement of already established proof of concept, the following programs could mature into significant opportunities for CSCRM and the region.

Dr. Gerson is partnering with Lentigen, Inc, of Gaithersburg, MD to develop a gene therapy approach to treating brain tumors. The goal of this project is to increase the patient’s resistance to a specific chemotherapy drug by genetically altering the patient’s hematopoietic stem cells. This group has demonstrated the efficacy and safety of this approach in preclinical models and has clinical grade procedures and reagents compliant with FDA guidelines in place.  Dr. Gerson plans to file an IND application with the FDA in 2009 and is prepared to initiate this trial in late 2009.

In the industrialized world, arthritic diseases affect approximately 20% of the general population and more than 60% of people over 65. Joint disease therapies therefore have a gigantic potential market. Jean Welter (CWRU) and Adam Lambert (Oakwood Laboratories) are teaming up to develop a combination product comprised of a drug and Oakwood’s proprietary sustained release technology to treat arthritic disease. Sustained-release formulations have the potential to maintain constant or defined drug levels within the joint space over a period of several weeks to several months. Screening studies on high-throughput cells culture systems developed at CWRU will include examining the effects of the delivery vehicle on differentiating and differentiated bone marrow derived mesenchymal stem cells (MSCs) and cartilage forming cells (chondrocytes). 

An additional project in this therapeutic area involves Eben Alsberg of CWRU and Orthopediatrics of Warsaw, IN.  Microspheres are very small balls made of biodegradable materials which can be tuned to release a specific amount of drug over a prolonged period of time.  With the proper drug and dosing, this procedure will tell the patient’s cells to create cartilage.  Specifically, the patient’s adipose derived stem cells (ADSCs) or MSCs will be grown with the microspheres for 24-48 hours before being mixed with a gel material and injected into the patient’s cartilage defect.  The cells will then create cartilage and repair the damaged tissue.

Bruce Trapp (CC) and commercial partner, Vertex Pharmacetuicals of Cambridge, MA, have identified a cell in the adult human brain that displays characteristics of a multi-potent stem cell. These cells can be reliably isolated and purified and can give rise to mature central nervous system (CNS) cells like neurons, astrocytes, and oligodendrocytes in culture. These cells have the potential, therefore, to treat a variety of neurodegenerative diseases, including multiple sclerosis (MS), Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, stroke, and spinal cord injury. Dr. Trapp has demonstrated that these cells have an unprecedented capability to repair myelin in an animal model of human myelin disease. The goal of the present proposal is to extend this work to develop and commercialize therapeutic treatments using stem cells isolated from adult animals for treating neurodegenerative diseases and spinal cord injury. 

Pilot programs
The pilot projects represent early stage, cutting edge scientific projects that were developed in the Center. While these projects are at an early stage, they were selected based upon their significance to the field and their potential economic impact if successfully matured. Funding for the three projects will be accompanied by a subset of eight new pilot projects determined through review by CSCRM oversight committees.

Paul Tesar (CWRU), Horst von Recum (CWRU) and Jeremy Rich (Cleveland Clinic and Co-Director of CSCRM) will establish a Pluripotent Stem Cell Facility within CWRU and the Clinic. Pluripotent stem cells provide a unique model system to study human development and disease. These cells are capable of perpetual growth in culture and have the ability to differentiate into all tissues of the human body like embryonic stem cells. Pluripotent cells can now be derived from non-embryonic sources. These cells, termed induced pluripotent stem cells (iPS cells), can be readily formed from a simple skin biopsy of any human patient.  This facility will be the first of its kind in that State of Ohio and will position the State as a global leader in the next phases of stem cell biology and regenerative medicine. 

Cell Targeting, Inc. is a company based on work conducted at CWRU by James Dennis and Arnold Caplan, and is actively investigating various applications of cell targeting methodologies to a variety of disease. These cell “paints” are newly-developed reagents that use a proprietary method for directing stem cells to specific organs and tissues and can be applied to nearly any stem cell therapeutic application. This project will apply this technology to directing umbilical cord blood stem cell transplantation, which is currently limited in utility because of low cell numbers and slower engraftment.

The last pilot project is focused on imaging solid tumors and represents collaboration between Zhenghong Lee (UHCMC) and Jeremy Rich (Cleveland Clinic). This group and others have demonstrated that cancer stem cells are resistant to conventional therapy, promote tumor angiogenesis, and invade and metastasize into normal tissues. The goal of this project is to develop a method to non-invasively image cancer stem cells through the development of radiolabeled tracers.

CSCRM Administration
Led by Debra Grega and Michael Gilkey, the CSCRM Administration is responsible for coordinating, accounting and reporting on all of these projects, continuing and creating education programs on stem cells and regenerative medicine for middle school through graduate level students, executing a biennial international stem cell conference (MSC 2009), interfacing and cultivating new commercial interactions, developing new research collaborations within the State as well as internationally, and representing the Center in scientific conferences and public events. The CSCRM Pilot Project Program will award eight $50,000 grants to CSCRM members to advance new technologies.

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About the Center for Stem Cell & Regenerative Medicine
The Center for Stem Cell and Regenerative Medicine is a multi-institutional center composed of over 100 investigators from Case Western Reserve University, University Hospitals Case Medical Center, the Cleveland Clinic, Athersys, Inc., and Ohio State University. Building on the 30 year history of adult stem cell research in northeast Ohio, the Center was created in 2003 with a $19.4 million award from the State of Ohio as a Wright Center of Innovation. An additional $8 million award in 2006 from the State of Ohio's Biomedical Research and Commercialization Program further validated the Center's ability to achieve its mission to utilize human stem cell and tissue engineering technologies to treat human disease.  In 2009, $5 million was awarded by the Ohio Third Frontier Program to continue the commercialization of new stem cell and related technologies.  Since its inception, CSCRM has effectively identified and developed appropriate stem cell therapeutics into clinical therapies and commercial biomedical opportunities based on preclinical work at Case Western Reserve University and the Cleveland Clinic; clinical validation studies at University Hospitals and Cleveland Clinic; commercial translation of new technologies by Oakwood Laboratories, Orthopediatrics and Cell Targeting; and new commercially sponsored clinical trials in Ohio by Athersys and Juventas Therapeutics.  http://www.thestemcellcenter.org

About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.

Annually, the School of Medicine trains more than 770 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report “Guide to Graduate Education.”

The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.