[GRG] antibody halts wasting conditions (cachexia)


Contact: Teresa Herbert
Dana-Farber Cancer Institute

Antibody halts cancer-related wasting condition

Study pinpoints a molecular cause of cachexia, and hints at a
potential treatment

BOSTON – New research raises the prospect of more effective
treatments for cachexia, a profound wasting of fat and muscle
occurring in about half of all cancer patients, raising their risk
of death, according to scientists from Dana-Farber Cancer Institute.

Many strategies have been tried to reverse the condition, which may
cause such frailty that patients can’t endure potentially life-
saving treatments, but none have had great success.

Scientists reporting in the July 13 advanced online edition of
Nature, led by Bruce Spiegelman, PhD, demonstrated that in mice
bearing lung tumors, their symptoms of cachexia improved or were
prevented when given an antibody that blocked the effects of a
protein, PTHrP, secreted by the tumor cells. PTHrP stands for
parathyroid hormone-related protein, and is known to be released
from many types of cancer cells.

The scientists said their findings are the first to explain in
detail how PTHrP from tumors switches on a thermogenic (heat-
producing) process in fatty tissues, resulting in unhealthy weight

This tumor-derived protein, they found, stimulated “beige” or brown
fat cells mixed with stored white fat in the body, causing the
white fat to “brown” – that is, generate heat and cause weight loss
even when the animals were at rest.

The researchers carried out two experiments using mice that
developed lung tumors and cachexia. In one, they administered a
polyclonal antibody that specifically neutralizes PTHrP and found
that it prevented the wasting almost completely, while untreated
animals became mildly cachexic.

In a second experiment, the antibody treatment prevented the loss
of muscle mass and improved muscle function, while control animals
developed severe muscle-wasting.

“You would have expected, based on our first experiments in cell
culture, that blocking PTHrP in the mice would reduce browning of
the fat,” said Spiegelman. “But we were surprised that it also
affected the loss of muscle mass, and improved health.”

The research suggested that PTHrP alone doesn’t directly cause
muscle wasting, yet blocking the protein’s activity prevents it.

Thus, the role of PTHrP “is definitely not the whole answer” to the
riddle of cachexia, noted Spiegelman, but may be a necessary part,
while other factors are also involved.

A collaborator on the study, Vickie E. Baracos, PhD, at the
University of Alberta in Edmonton, Canada, provided the blood of 47
patients with lung or colon cancer who were cachexic. Serkan Kir,
PhD, from the Spiegelman lab – and first author on the paper –found
increased levels of PTHrP in 17 of the patients. Those patients had
significantly lower lean body mass and were producing more heat
energy at rest than were the other patients in the group.

It may turn out that the PTHrP mechanism is responsible for
cachexia in a subset, but not all, cancer patients, Spiegelman
suggested. Before trying the anti-PTHrP antibody in human patients,
he said, “clinicians would probably first want to find out if the
protein is elevated in certain cancers, and determine which
patients would be good candidates for a clinical trial.”

Barrett Rollins, MD, PhD, Dana-Farber’s chief scientific officer,
commented that the report from Spiegelman and his colleagues
“provides a new roadmap for developing a rational, mechanistically
based treatment for this incredibly debilitating condition that
occurs in such a large number of our patients. Until now we’ve had
no truly effective way to reverse this horrible complication.”

Patients with upper gastrointestinal and pancreatic cancers are the
most likely to develop cachexia, and the condition affects about 80
percent of terminal cancer patients. Current strategy is to give
appetite stimulants and nutrient supplements, along with
medications to counteract some of the molecular pathways believed
to underlie the wasting process, but with limited success.



About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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