Mayo’s “Smart” Adult Stem Cells Repair Hearts

(BUSINESS WIRE)--Mayo Clinic investigators, with Belgian collaborators, have demonstrated that rationally “guided” human adult stem cells can effectively heal, repair and regenerate damaged heart tissue. The findings — called “landmark work” in an accompanying editorial — appear in today’s Journal of the American College of Cardiology.

Stem cells isolated from patients have normally a limited capacity to repair the heart. This innovative technology boosts the regenerative benefit by programming adult stem cells to acquire a cardiac-like profile. Primed by a cocktail of recombinant cardiogenic growth factors, mesenchymal stem cells (MSCs) harvested from the bone marrow of a cohort of patients with coronary artery disease showed “superior functional and structural benefit without adverse side effects” over a 1-year follow-up in a model of heart failure according to the study.

Significance of the Findings

“These findings provide proof-of-principle that “smart” adult stem cells have added benefit in repairing the heart, providing the foundation for further clinical evaluation,” says Andre Terzic, M.D., Ph.D., Mayo Clinic researcher and senior investigator of the study. “The successful use of guided “lineage specified” human stem cells is based on natural cardiogenic cues” adds Atta Behfar, M.D., Ph.D. first author of the study. The pre-clinical data reported in this seminal paper have cleared the way for safety and feasibility trials in humans, which were recently conducted in Europe.

In their editorial, Eduardo Marban, M.D., Ph.D., and Konstantinos Malliaras, M.D., of Cedars-Sinai Heart Institute, in Los Angeles describe the Mayo approach as a “boot camp” for stem cells and also write that the study “… provides the first convincing evidence that MSCs, at least in vitro, can in fact become functional cardiomyocytes (heart cells)...”

The long-term potential of the findings include development of an effective regenerative medicine therapy for patients with chronic heart failure.

How It Was Done

Researchers obtained bone marrow-derived stem cells from heart disease patients undergoing coronary bypass surgery. Testing of these stem cells revealed that cells from two of 11 individuals showed an unusual capacity for heart repair. These rare cells demonstrated upregulated genetic transcription factors that helped identify a molecular signature identifying highly regenerative stem cells. The cardiogenic cocktail was then used to induce this signature in non-reparative patient stem cells to program their capacity to repair the heart. Mouse models with heart failure, injected with these cells, demonstrated significant heart function recovery along with improved survival rate after a year, compared to those treated with unguided stem cells or saline.

Specifically, researchers found that the heart tissue healed more effectively; that human cardiac and vascular cells were found participating in the regeneration, repair and strengthening of heart structures within the area of injury; and that scars and vestiges of heart damage appeared to fade away.

Authors include Atta Behfar, M.D., Ph.D.; Satsuki Yamada, M.D., Ph.D.; Ruben Crespo-Diaz; Jonathan Nesbitt; Lois Rowe; Carmen Perez-Terzic, M.D., Ph.D.; Andre Terzic, M.D., Ph.D. of Mayo Clinic; Vinciane Gaussin, Ph.D. and Christian Homsy, M.D., Cardio3 Biosciences, Mont-Saint-Guibert, Belgium; and Jozef Bartunek, M.D., Cardiovascular Center, Aalst, Belgium.

The research was supported by the National Institutes of Health, the American Heart Association, the Marriott Heart Disease Research Program, Cardio 3 Biosciences, the Ted Nash Long Life Foundation, the Ralph Wilson Medical Research Foundation, the Mayo Clinic General Mills Clinician-Investigator Fellowship, and Mayo Clinic.

Mayo Clinic and Drs. Andre Terzic and Atta Behfar have a financial interest associated with technology related to this research program. In accordance with the Bayh-Dole Act, Mayo Clinic has licensed that technology to Cardio 3 Biosciences in exchange for equity. No royalties have accrued to date to the institution or the inventors.

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MERIAL Receives Full License Approval for ONCEPT(TM) Canine Melanoma Vaccine

/PRNewswire/ -- Merial, a world-leading animal health company, has gained full-licensure from the U.S. Department of Agriculture for ONCEPT(TM) Canine Melanoma Vaccine, DNA. ONCEPT is a breakthrough vaccine indicated for aiding in extending survival of dogs with stage II or stage III oral canine melanoma, a common yet deadly form of cancer in dogs.

ONCEPT is the first and only USDA-approved, therapeutic vaccine for the treatment of cancer - in either animals or humans.

Traditionally, dogs with stage II or stage III malignant melanoma survive less than five to six months when treated with surgery alone.(1) Clinical studies of ONCEPT demonstrated significantly longer life spans even in dogs with stage II or stage III of oral melanoma. In fact, median survival time of dogs treated with ONCEPT could not be determined because more than 50 percent of the treated dogs were still living melanoma-free at the conclusion of the study or died of unrelated illness.(2)

Canine oral melanoma is a common type of cancer in dogs and is the most common malignant tumor of the dog's mouth. It can also be seen in the nail and footpad.(3) Canine melanoma may be seen in any breed and is a highly aggressive cancer that frequently spreads throughout the body, including the lymph nodes, liver, lungs and kidneys.(4) To date, the most common treatments for this form of cancer have been radiation and surgery to establish local tumor control. Canine oral melanoma, however, has a high propensity to metastasize to other parts of the body and is often resistant to chemotherapy.(2,3)

"Canine melanoma spreads readily, and, unfortunately, existing treatments have not succeeded in controlling the disease," said Dr. Bob Menardi, a veterinarian and spokesperson for Merial. "ONCEPT is a new adjunct treatment option for dogs that have been diagnosed with this often fatal disease."

The vaccine was developed through a partnership between Merial and Memorial Sloan-Kettering Cancer Center. While Memorial Sloan-Kettering was testing a human melanoma vaccine, they received an inquiry from Dr. Philip Bergman - who at the time was with Animal Medical Center, and currently with Brightheart Veterinary Center - seeking novel treatments for canine melanoma. The discussions resulted in clinical trials of the Memorial Sloan-Kettering melanoma vaccine, and subsequent parallel trials by Dr. Bergman and Memorial Sloan-Kettering refined the dosage and protocol to the current therapeutic regimen for dogs. Dr. Bergman completed the initial clinical work on ONCEPT at Animal Medical Center in New York.

"We're very excited about continuing research into this vaccine to explore the potential implications it has for humans. We hope this will result in improved cancer treatment for all," explained Jedd D. Wolchok, MD, PhD, a medical oncologist who specializes in immunotherapy on the Melanoma and Sarcoma Service at Memorial Sloan-Kettering and also Associate Director of the Ludwig Center for Cancer Immunotherapy.

The USDA issued a conditional U.S. Veterinary Biological Product License for ONCEPT in 2007. During the period of conditional licensure, ONCEPT was available to veterinary oncologists as Merial conducted additional research to further support the safety and efficacy of the vaccine.

The results of that research led to the full licensure of ONCEPT. Merial obtained licensing rights from Memorial Sloan-Kettering and Dr. Philip Bergman, and, using their access to and experience with DNA vaccine technology licensed from Vical Incorporated (NASDAQ:VICL) , completed the industrialization and regulatory requirements for full licensure. The vaccine will be administered via a Canine Transdermal Device, which delivers the vaccine without the use of a needle.(5) The device was developed in conjunction with Bioject, Inc., a Portland-based drug delivery company (OTC Bulletin Board: BJCT).

"The Canine Transdermal Device makes administration of the vaccine easy and quick for oncologists and their patients, leaving one less worry for dog owners dealing with their pet's cancer treatment" said Dr. Richard Stout, executive vice president and chief medical officer of Bioject. "We are proud to work with Merial in bringing this breakthrough product to market."

"The approval of ONCEPT is a milestone in the cancer vaccine field and a significant advancement for our DNA delivery technology platform," said Vijay B. Samant, Vical's President and Chief Executive Officer. "Therapeutic vaccines -- the holy grail of vaccinology -- are delivered after disease onset to impede disease progress for the patient's benefit. We believe this achievement is a major step toward the initial approvals of therapeutic vaccines for humans."

ONCEPT is available for use by specialists practicing veterinary oncology, so pet owners will want to ask their veterinarians about how best to access this treatment option.

Merial is a world-leading, innovation-driven animal health company, providing a comprehensive range of products to enhance the health, well-being and performance of a wide range of animals. Merial employs approximately 5,700 people and operates in more than 150 countries worldwide. Its 2009 sales were $2.6 billion. Merial is the Animal Health subsidiary of sanofi-aventis. For more information, please see www.merial.com.

Bioject Medical Technologies Inc., based in Portland, Oregon, is an innovative developer and manufacturer of needle-free injection therapy systems (NFITS). NFITS provide an empowering technology and work by forcing medication at high speed through a tiny orifice held against the skin. This creates a fine stream of high-pressure fluid penetrating the skin and depositing medication in the tissue beneath. The Company is focused on developing mutually beneficial agreements with leading pharmaceutical, biotechnology, and veterinary companies. For more information about Bioject, visit www.bioject.com.

Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company's DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. Additional information on Vical is available at www.vical.com.

(1) Bergman PJ, Wolchok JD. Of Mice and Men (and Dogs): development of a xenogeneic DNA vaccine program for canine malignant melanoma. Cancer Therapy 2008;6:817-826.

(2) Data on file at Merial. Study 05-171. 2009.

(3) Bergman PJ, et al. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006;24:4582-4585.

(4) Liao JCF, et al. Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma. Cancer Immunity 2006;6:8-17.

(5) ONCEPT product label.

ONCEPT(TM) is a trademark of Merial.

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FDA Clears New CDC Test to Detect Human Influenza

The U.S. Food and Drug Administration (FDA) today cleared a new test
developed by the U.S. Centers for Disease Control and Prevention (CDC)
to diagnose human influenza infections and the highly pathogenic
influenza A (H5N1) viruses.

The device, called the Human Influenza Virus Real-Time RT-PCR Detection
and Characterization Panel (rRT-PCR Flu Panel), uses a molecular biology
technique to detect flu virus and differentiate between seasonal and
novel influenza.

The device is used to isolate and amplify viral genetic material present
in secretions taken from a patient's nose or throat. The viral genetic
material is labeled with fluorescent molecules, which are then detected
and analyzed by a diagnostic instrument called the Applied Biosystems
7500 Fast Dx, also cleared today by the FDA for diagnostic use
simultaneously with the CDC's rRT-PCR Flu Panel.

The test panel and diagnostic system can detect and identify commonly
circulating human influenza viruses as well as influenza A (H5N1)
viruses. Results can be available within four hours and the system can
test multiple samples at once.

"This is a significant achievement for public health surveillance," HHS
Secretary Mike Leavitt said. "The test allows us to better support
laboratories on the front line of influenza testing in the United States
and abroad."

"The application of the test to detect an emergent influenza virus would
be especially important in the early stages of a pandemic," Secretary
Leavitt added. "This breakthrough allows for a more timely detection of
a pandemic virus, which helps in determining when to begin broad control
strategies as well as life-saving mitigation measures, such as closing
schools, cancelling social gatherings and informing businesses to begin
work-at-home policies."

The test will be available to CDC-qualified laboratories for diagnosing
influenza this fall, and some laboratories will be able to obtain
reagents (certain substances used in the testing process) at no cost.
This test should help ensure the accuracy of influenza testing results
among the different qualified laboratories that conduct influenza
subtype testing.

"This new test provides us another tool in our toolbox to fight seasonal
influenza, a virus that unfortunately kills thousands of people each
year in the United States," said CDC Director Dr. Julie Gerberding.
"We'll now be able to detect influenza in the community faster, which
allows us to take steps more quickly to protect and save lives."

Since influenza viruses are always changing, test reagents need to be
evaluated regularly against circulating viruses to ensure the
sensitivity and specificity of the test to diagnose current influenza
viruses.

"Because the test can tell the difference between seasonal human
influenza viruses and novel viruses, it will also provide qualified
laboratories with a means to rapidly detect new influenza viruses that
have not been identified yet and that could pose a pandemic risk," said
FDA Principal Deputy Commissioner and Chief Scientist Dr. Frank Torti,
M.D., M.P.H.

The CDC, Applied Biosystems of Foster City, Calif., and the Association
of Public Health Laboratories collaborated on the development of this
new test. State public health laboratories in Virginia, Iowa,
California, Massachusetts, Wisconsin, and Washington performed clinical
evaluations of the new flu panel.

Scientists around the world are concerned that the H5N1 virus could one
day mutate and acquire the properties needed to quickly spread between
people, resulting in a pandemic. H5N1 viruses circulate widely in birds
in Asia, Africa and Europe and have caused human illness and death.
These viruses have never been detected in the Americas.

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