Growing heart muscle: A peptide called neuroregulin1 can stimulate heart muscle cells (red) in rats to divide. Markers of dividing cells (red) are shown in green/yellow. Cell nuclei are shown in blue.   Credit: Bersell et al, Cell

 

 

A startup aims to repair heart damage with peptides that trigger the proliferation of heart cells

 

MIT Technology Review, April 19, 2010, by Emily Singer  –  While the human heart was once thought incapable of regeneration, growing evidence shows that even the adult heart can grow new cells, albeit slowly. Roger Hajjar, director of the Cardiovascular Research Center at the Mount Sinai School of Medicine, in New York, and Bernhard Kuhn, a cardiologist at Children’s Hospital Boston, aim to harness this regenerative ability to change how heart disease is treated. They cofounded a startup called CardioHeal, based in Brookline, MA, to develop peptide drugs that can spur growth of new heart muscle cells in the human body.

The scientists have identified a pair of peptides that can stimulate new cell growth and improve heart function in rodents induced to have heart attacks. Hajjar’s lab at Mt. Sinai is now testing one of the peptides, periostin, in pigs induced to have heart attacks. Because these animals have hearts similar in size to humans, they provide a good model for testing new therapies prior to human clinical trials. Preliminary results show that injecting the peptide into the pericardium, the lining around the heart, seems to help. “They’re not completely back to normal, but they’re much better,” says Hajjar.

Researchers hope the molecules will ultimately provide an alternative approach to treating heart disease. Currently, people who suffer a heart attack get medication, such as beta blockers, to make it easier for the heart to beat, and surgery to clear blocked arteries. “But none are directed at giving new heart muscle back after myocardial infarction,” says Kuhn. The cardiologist says patients regularly ask him if the treatment is available for them, part of the reason he decided to found the company. “I’ve been getting patient requests for a couple of years, but we don’t have an open trial or anticipate opening one anytime soon.”

Cardioheal’s approach is, to some degree, in competition with stem-cell therapy, which is already being tested in humans. Scientists are working on different ways of harvesting and delivering stem cells to patients with heart disease, and clinical trials have so far yielded mixed results. Transplanted cells appear to have difficulty surviving and integrating into their new environment. In fact, some scientists suggests that benefit of cell transplants comes from the cells ability to stimulate innate growth. Triggering this process with peptides “may be a simpler method of treatment of certain conditions such as cardiomyopathy [an enlarged heart] where the problem is lack of viable, contractile heart muscle cells,” says Amish Raval, a cardiologist at the University of Wisconsin, in Madison, who is not involved with the company.

Cardioheal still has a number of questions to address before testing the peptides in patients. “What is the least invasive way of getting it to the patient’s heart?” asks Hajjar. “At what point after heart attack would you deliver this–early, late, when a patient develops congestive heart failure?” Researchers say they haven’t seen adverse effects in treated animals, but extensive safety testing needs to be done before human trials. “Tumor formation, noncardiac muscle tissue formation, causing dangerous arrhythmias needs to be systematically evaluated in animal models with broad dose ranges tested,” says Ravel. “I would be interested in knowing whether the cardiac cells actually integrate with the environment in the heart, or just independently contract. There has to be electrical and mechanical integration for this treatment to work.”

USDOD, April 19, 2010, by John Ohab  –  By modifying an ink jet printer and growing skin cells from a patient’s body, an Army research lab has developed an amazing treatment for severe burns: printing new skin.

Once the patient’s skin cells are in a sterile ink cartridge, a computer uses a three dimensional map of the wound to guide the printing.

“The bio-printer drops each type of cell precisely where it needs to go,” explains Kyle Binder, a biomedical scientist at the Armed Forces Institute of Regenerative Medicine’s Wake Forest lab. “The wound gets filled in and then those cells become new skin.”

Special thanks to the National Defense Education Program for providing this insider’s view of every day work undertaken by Defense Department scientists and engineers.

Printing New Human Skin

By Christen N. McCluney
Defense Media Activity

April 19, 2010  –  Researchers at the Walter Reed Army Institute of Research are discovering new ways to combat and prevent the spread of malaria.

“Every conflict the U.S. has been in we’ve been faced with malaria,” said Army Col. Christian Ockenhouse, director of the U.S. Military Malaria Vaccine Program, during an April 14 interview on the Pentagon Channel podcast “Armed with Science: Research and Applications for the Modern Military.

Malaria is a parasitic disease which infects red blood cells, Ockenhouse said. It’s transmitted through the bite of a female mosquito, goes to the liver to develop, and emerges after five days into the bloodstream to cause the disease.

0:00 / 0:00DownloadRight-click and save as to download.

to the full interview or read the transcript.

Most people believe malaria is a disease of the past, but it has not disappeared, he said. In sub-Saharan Africa, 3,000 children die every day from the disease, he noted, which also can target adults, including U.S. troops serving in Afghanistan, South America and Africa.

In the military, malaria impacts readiness and missions, and measures are implemented to combat the disease, Ockenhouse said. Using insect repellant and camouflage face paint with repellent in it, wearing uniforms impregnated with insecticides and employing bed nets can help to prevent malaria.

One of the important measures to prevent the disease is taking anti-malaria pills. This pill regime is one of the most effective preventative methods, Ockenhouse said, but it has to be performed daily. “Often time soldiers forget or don’t take it if they don’t see any symptoms,” he said.

The researchers are working with the U.S. Food and Drug Administration (FDA) in three areas to protect servicemembers and children against malaria. First, they are developing a highly safe, highly effective vaccine. A second area is to develop better diagnostics, which would allow earlier detection and treatment of the malaria parasite in the blood. Third, they are developing new anti-malarial drugs to prevent infection and treat those that have it.

The researchers also are developing a medication for severe malaria. Ockenhouse spoke of an in-house program designed not only for early-stage research and development, but also to test new drugs against malaria in late-stage clinical trials intended for FDA approval.

The group also works overseas with laboratories located in Kenya, Thailand, Tanzania, Mali, South America and Peru.

“We are ambassadors in the countries where we work. We are there to lend assistance to their public health initiatives, which includes helping these countries test malaria vaccines, drugs and diagnostics and aiding in infrastructure and capacity development.”

The researchers also have assisted in the development of the world’s most advanced malaria vaccine that is being tested in 16,000 infants in 11 different countries. Preliminary studies indicate that use of the vaccine can reduce malaria by 50 percent. When licensed and made available the vaccine could save hundreds of thousands, if not millions, of children’s lives, Ockenhouse said.

“We are at the forefront of many endeavors in drugs and vaccines,” Ockenhouse said. “The DoD should be particularly proud that it is stepping up to the plate and leading the world’s efforts on this disease.”

Silk on the brain: Thin, flexible electrodes mounted on top of a biodegradable silk substrate could provide a better brain-machine interface. The device wraps around the crevices in the surface of the brain, as shown on this model.  Credit: John Rogers

 

 

Gentler, softer electrodes wrap around the folds of the brain to take higher-resolution measurements

MIT Technology Review, April 19, 2010, by Katherine Bourzac  –  Doctors can put arrays of electrodes on the surface of the brain to pinpoint the source of epileptic seizures; patients can use such electrodes to control a computer cursor. But it’s still not safe to leave these devices in the brain over the long term, and that’s a quality that needs to be developed before researchers can develop better brain-computer interfaces.

Now a group of researchers is building biocompatible electronics on thin, flexible substrates. The group hopes to create neural interfaces that take higher-resolution measurements than what’s available today without irritating or scarring brain tissue.

“Biocompatibility is a major challenge for new generations of medical implants,” says Brian Litt, professor of neurology and bioengineering at the University of Pennsylvania Medical School. “We wanted to make devices that are ultrathin and can be inserted into the brain through small holes in the skull, and be made out of materials that are biocompatible,” he says. Litt is working with researchers at the University of Illinois at Urbana-Champaign who are building high-performance flexible electronics from silicon and other conventional materials on substrates of biodegradable, mechanically strong silk films provided by researchers at Tufts University.

This week in the journal Nature Materials, the team reports using a silk electrode device to measure electrical activity from the surface of the brain in cats. Silk is mechanically strong–that means the films can be rolled up and inserted through a small hole in the skull–yet can dissolve into harmless biomolecules over time. When it’s placed on brain tissue and wetted with saline, a silk film will shrink-wrap around the surface of the brain, bringing electrodes with it into the wrinkles of the tissue. Conventional surface electrode arrays can’t reach these crevices, which make up a large amount of the brain’s surface area.

“A device like this would completely open up new avenues in all of neuroscience and clinical applications,” says Gerwin Schalk, a researcher at the Wadsworth Center in Albany, NY, who is not affiliated with the silk electrode group. “What I foresee is placing a silk-based device all around the brain and getting a continuous image of brain function for weeks, months, or years, at high spatial and temporal resolution.”

The advantage of surface electrodes over implanted ones is that they don’t cause scarring, says Andrew Schwartz, professor of neurobiology at the University of Pittsburgh. In 2008, Schwartz demonstrated that a monkey with an electrode in its brain can control a prosthetic arm to feed itself. “This design is even better because it has a relatively small feature size and is flexible–it could make these implants less traumatic,” he says. “What would really be nice is if you could amplify the signal near where you pick it up to reduce noise, and multiplex the signal to cut down on the number of wires needed,” says Schwartz.

The silk electronics researchers say this is their next step, and one of the major promises of the technology. They’ve already demonstrated thin, flexible silicon transistor arrays built on silk, and tested them in animals–just not in the brain yet. Schwartz says other groups have recognized the importance of multiplexing and signal amplification, but have been working with rigid circuit boards that are not as biocompatible. Adding these active components would reduce the number of wires needed in these implants, which today require one wire per sensor. And active devices could respond to brain activity to provide electrical stimuli, or release drugs. (One of the collaborators on the silk project, David Kaplan at Tufts University, has demonstrated that silk devices implanted in the brain in small animals can deliver anti-epilepsy drugs.)

Adding transistors to the electronics is currently a design challenge, says John Rogers, professor of materials science and engineering at the University of Illinois at Urbana-Champaign. The electrode-array design his group found to be most compatible with brain tissue is a mesh–solid sheets won’t wrap around brain tissue as effectively. And adding silicon transistors to the mesh is more difficult than doing so on a solid substrate. Still, says Rogers, all the major pieces are in place and just need to be integrated. With further development and testing to prove the devices are safe, says Rogers, “we hope this will be the foundation for new higher quality brain-machine interfaces.”

Research and Licensing Agreement Allows Stemgent to Offer Research Compounds from Pfizer

BOSTON & NEW YORK, April 19, 2010 (BUSINESS WIRE) — –Dr. Ruth McKernan, CSO of Pfizer Regenerative Medicine, to Join Stemgent’s SAB

Stemgent, Inc. and Pfizer Inc. /quotes/comstock/13*!pfe/quotes/nls/pfe (PFE 16.76, -0.03, -0.18%) today announced a collaboration and research licensing agreement that will lead to certain research reagents developed or discovered by Pfizer being made available to the global research community through Stemgent. Stemgent provides research tools and services to institutions, companies and universities in advancing in vitro and in vivo non-human stem cell research.

According to the agreement, scientists involved in cell-based research will now be able to purchase fully licensed compounds with pharmaceutical modes of action as off-the-shelf products for use in non-clinical experiments. It is hoped that along with other Stemgent offerings, the materials will greatly benefit scientists working in a diverse range of stem cell and cell-based applications, including neuroscience, cancer and metabolic disease.

As part of the agreement, Pfizer and Stemgent will form a joint research committee to review and evaluate the collaboration’s progress, coordinate results publication, monitor information and materials exchange between the two parties, nominate compounds and provide guidance relating to research tools for use in stem cell research.

“We are pleased to form this partnership with Stemgent,” said Ruth McKernan, Ph.D., chief scientific officer of Pfizer Regenerative Medicine. Dr. McKernan will also join Stemgent’s scientific advisory board. “We applaud the efforts Stemgent has made in bringing important research tools to the stem cell community. We all need research tools such as the molecules Stemgent can offer to dissect the pathways involved in stem cell biology and to advance our understanding of the science. I am delighted to join other industry and academic leaders on Stemgent’s Scientific Advisory Board.”

Commenting on the collaboration, Ian Ratcliffe, President and Chief Executive Officer of Stemgent, said, “This is an important step for the scientific community as it increases our potential small molecule product offerings at a time when stem cell research gathers momentum and size around the world. We are especially pleased to have Dr. McKernan on our SAB; her experience and intellect bring tremendous value to our already globally respected group of scientific advisors.”

About Pfizer Inc: Working together for a healthier world(TM)

At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world’s best-known consumer products. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more about our commitments, please visit us at www.pfizer.com.

About Stemgent

Stemgent advances stem cell science by providing proprietary reagents and tools developed by some of the world’s leading stem cell scientists. Stemgent’s product offering has been specifically optimized for and screened against stem cells, and includes small molecules for pluripotency, self-renewal, and differentiation, viral-delivered transcription factors, matrices, cell lines, cytokines, antibodies, transfection reagents, and more. This unique product mix is designed to serve researchers who study stem cell biology and regenerative medicine, and those who use cells derived from stem cells as tools to advance their understanding of major diseases. With dual science facilities in Boston, Massachusetts, and San Diego, California, Stemgent is well positioned to serve these major research markets. For more information on Stemgent, please visit: http://www.stemgent.com.