(Press-News.org) May 5, 2013 — (Bronx, NY) — Cancer chemotherapy can cause peripheral neuropathy—nerve damage often resulting in pain and muscle weakness in the arms and legs. Now, researchers at Albert Einstein College of Medicine of Yeshiva University have discovered that chemo also induces an insidious type of nerve damage inside bone marrow that can cause delays in recovery after bone marrow transplantation. The findings, made in mice and published online today in Nature Medicine, suggest that combining chemotherapy with nerve-protecting agents may prevent long-term bone marrow injury that causes anemia and may improve the success of bone marrow transplants.
Constantly regenerating and maturing, the hematopoietic (blood-producing) stem cells in our bone marrow produce billions of red blood cells (RBC) every day. Cancer chemotherapy is notorious for injuring the bone marrow, leading to anemia, or low RBC counts. But just how chemotherapy harms the bone marrow has not been clear.
Anemia can lead to numerous health problems including chronic fatigue, tachycardia (abnormally rapid heartbeat), cognitive impairment, shortness of breath, depression and dizziness. In addition, studies have shown that cancer patients who develop anemia have a 65 percent increased risk of death compared with cancer patients without anemia.
In an earlier study, senior author Paul Frenette, M.D., professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein, found that sympathetic nerves within bone marrow direct the movement of hematopoietic stem cells. (The body's sympathetic nervous system helps in controlling most internal organs—increasing heart rate and dilating the pupils of the eye, for example.)
"Since many chemotherapies used in cancer treatment are neurotoxic, we wondered whether they might also damage sympathetic nerves in bone marrow itself, impairing the ability of hematopoietic cells to regenerate and to manufacture RBCs," said Dr. Frenette. "This possibility hadn't been examined before."
Dr. Frenette and his colleagues treated mice with seven cycles of cisplatin, a common chemotherapy drug with known neurotoxic effects. The cisplatin caused peripheral neuropathy problems similar to those seen in cancer patients. The mice were then given fresh bone marrow transplants to see how well their marrow would regenerate. Despite receiving fresh stem cells, the cisplatin-treated mice had delayed recovery of blood counts compared to controls—suggesting that the prior cisplatin treatments had affected the bone marrow and prevented hematopoietic stem cells from regenerating. By contrast, mice treated with carboplatin—a non-neurotoxic chemotherapy—recovered their ability to produce blood after bone marrow transplantation.
To confirm that healthy sympathetic nerves in the bone marrow are needed to regenerate hematopoietic stem cells and produce RBCs, the researchers selectively damaged sympathetic nerves in bone marrow using chemicals or genetic engineering. In both cases, the mice with the damaged sympathetic nerves were less able than control mice to recover after bone marrow transplant.
The researchers found that injury to these nerves could be reduced by giving mice nerve-protecting agents along with chemotherapy. Mice treated with seven cycles of cisplatin along with 4-methylcatechol (an experimental drug that reportedly protects sympathetic nerves) showed improved response to bone marrow transplantation, compared to controls.
Dr. Frenette and his colleagues now plan to look for compounds that can protect sympathetic nerves in the bone marrow without reducing the effectiveness of cancer chemotherapies.
###
The title of the paper is "Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration." The lead author of the paper is Daniel Lucas, Ph.D., a postdoctoral reseacher in Dr. Frenette's laboratory. Other Einstein contributors are Christoph Scheiermann, Ph.D., and Yuya Kunisaki, M.D., Ph.D. Additional co-authors are Andrew Chow, M.D./Ph.D. student, Icahn School of Medicine at Mount Sinai, New York, NY; Ingmar Bruns, M.D., Ph.D., Einstein and Heinrich Heine University, Dusseldorf, Germany; Colleen Barrick, National Cancer Institute, Frederick, MD; and Lino Tessarollo, Ph.D., National Cancer Institute.
This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK056638) and the National Heart, Lung, and Blood Institute (HL069438), both parts of the National Institutes of Health.
A patent application on this technology has been filed, which is currently available for licensing and further commercialization.
The authors declare no competing financial interests.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2012-2013 academic year, Einstein is home to 742 M.D. students, 245 Ph.D. students, 116 students in the combined M.D./Ph.D. program, and 360 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2012, Einstein received over $160 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center –Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit http://www.einstein.yu.edu and follow us on Twitter @EinsteinMed.
END
UCSF scientists controlled seizures in epileptic mice with a one-time transplantation of medial ganglionic eminence (MGE) cells, which inhibit signaling in overactive nerve circuits, into the hippocampus, a brain region associated with seizures, as well as with learning and memory. Other researchers had previously used different cell types in rodent cell transplantation experiments and failed to stop seizures.
Cell therapy has become an active focus of epilepsy research, in part because current medications, even when effective, only control symptoms and not underlying ...
SALT LAKE CITY, May 6, 2013 – University of Utah metallurgists used an old microwave oven to produce a nanocrystal semiconductor rapidly using cheap, abundant and less toxic metals than other semiconductors. They hope it will be used for more efficient photovoltaic solar cells and LED lights, biological sensors and systems to convert waste heat to electricity.
Using microwaves "is a fast way to make these particles that have a broad range of applications," says Michael Free, a professor of metallurgical engineering. "We hope in the next five years there will be some commercial ...
WASHINGTON, DC – Chemicals called polybrominated diphenyl ethers (PBDEs) have been used for decades to reduce fires in everyday products such as baby strollers, carpeting and electronics. A new study to be presented on Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting shows that prenatal exposure to the flame retardants is associated with lower intelligence and hyperactivity in early childhood.
"In animal studies, PBDEs can disrupt thyroid hormone and cause hyperactivity and learning problems," said lead author Aimin Chen, MD, PhD, assistant professor ...
WASHINGTON, DC – Regular exercise is touted as an antidote for many ills, including stress, depression and obesity. Physical activity also may help decrease violent behavior among adolescent girls, according to new research to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Researchers from Columbia University analyzed results of a 2008 survey completed by 1,312 students at four inner-city high schools in New York to determine if there was an association between regular exercise and violence-related behaviors.
"Violence ...
WASHINGTON, DC – Many high school football players say it's OK to play with a concussion even though they know they are at risk of serious injury, according to a study to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
The study of 120 high school football players in the Cincinnati area also found that one-quarter had suffered a concussion, and more than half acknowledged they would continue to play with symptoms of a concussion.
"These attitudes could leave young athletes vulnerable to injury from sports-related ...
WASHINGTON, DC —Bicycle helmets save lives, and their use should be required by law. That's the conclusion of a study to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
"This study highlights the importance of regulations in the promotion of safe exercise," said lead author William P. Meehan III, MD, FAAP, director of the Micheli Center for Sports Injury Prevention and the Sports Concussion Clinic at Boston Children's Hospital.
About 900 people die each year in bicycle crashes, three-quarters of them from head ...
WASHINGTON, DC – Many parents are putting their precious cargo at risk while driving, according to survey results that will be presented May 5 and 6 at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Researchers from the University of Michigan surveyed more than 600 parents to find out what distractions they face while driving with their children, whether they use age-appropriate child restraints and if they had ever been in a motor vehicle accident.
"Lots of attention has been given to distracted teen drivers. However, our results indicate ...
WASHINGTON, DC – Newspaper articles, TV shows and books are filled with horror stories of children placed in foster care. A new study bucks that trend by showing out-of-home placements can improve the emotional health of some youths who have been maltreated by a parent.
The study, led by Ann-Marie Conn, PhD, general pediatric academic fellow at University of Rochester Medical Center in New York, will be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Dr. Conn and her colleagues compared mental health problems in ...
WASHINGTON, DC – Nearly one in five children and teens found to be at risk for suicide report that there are guns in their homes, and 15 percent of those at risk for suicide with guns in the home know how to access both the guns and the bullets, according to a study to be presented Monday, May 6, at the Pediatric Academic Societies (PAS) annual meeting in Washington, DC.
Suicide is the second leading cause of death among young people ages 10 to 24 years in the United States, according to Centers for Disease Control and Prevention data. Nearly half of youths who die by ...
May 6, 2013 /Press Release/ –– Children living near toxic waste sites in lower and middle income countries such as India, Philippines and Indonesia may experience higher blood lead levels, resulting in a loss of IQ points and a higher incidence of mental retardation, according to a study presented today by Kevin Chatham-Stephens, MD, Pediatric Environmental Health Fellow at the Icahn School of Medicine at Mount Sinai, at the Pediatric Academic Societies (PAS) annual meeting on May 6 in Washington, DC.
The study titled, "The Pediatric Burden of Disease from Lead Exposure ...
