(Press-News.org) Researchers at Northwestern University Feinberg School of Medicine have developed the first animal model that duplicates the human response in rheumatoid arthritis (RA), an important step that may enable scientists to discover better medicines to treat the disease.
Corresponding and senior author Harris Perlman, associate professor of rheumatology at Feinberg, introduced his team's new prototype mouse model in a recent online issue of the Journal of Translational Medicine.
"This is the first time human stem cells have been transplanted into mice in order to find RA treatments," Perlman said. "We believe this will improve drug discovery because the reactions we observed were authentic human reactions."
Until now, scientists have relied on the common scientific method of using specially bred mice to find drugs to control RA. However, human and mouse immune systems differ dramatically, so studying RA in these mice does not give an accurate representation of how the disease functions in humans. In some cases, RA drugs that seemed promising based on results in mice failed in human clinical trials.
Mice implanted with human stem cells have been used before mainly to study infectious disease.
The Northwestern team injected day-old mice with human stem cells from umbilical cord blood, including white blood cells, which regulate immunity. Then, RA was introduced in the mice and suppressed with Enbrel®, a common first-line drug for joint inflammation in humans. This offered evidence that their immune systems were indeed replicating human defenses.
Scientists seek mouse models that mimic RA in humans in order to learn how the complex disease operates. In the last decade, researchers and physicians have found many subtypes of RA that originate on the molecular level and are each produced by different pathways in the body.
A debilitating disease, rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent inflammation around joint areas, predominantly in the wrist and fingers. The disease causes pain, swelling, stiffness and loss of function and can result in tissue destruction. Approximately 1.3 million people have the disease.
Onset of RA usually begins between ages 25 to 55, but recent studies reveal that the disease actually begins several years before symptoms appear. This has broadened the focus to create drugs that prevent RA or at least enable early diagnosis instead of trying to reduce symptoms once it is further along and difficult to control.
This is the second mouse model Perlman has developed to help discover better rheumatoid arthritis therapies. Earlier this year, he introduced a mouse model that develops RA and is predisposed to atherosclerosis, or hardening of the arteries, a common RA complication in humans.
Perlman called this first humanized mouse model "the tip of the iceberg" in terms of how it will help improve RA treatment. He added that future studies will involve harvesting stem cells in cord blood from mothers who have RA, so researchers can work with immune cells containing the disease's genetic makeup. Since the disease is influenced by genetics, the maternal immune cells will be transplanted in mice to pinpoint preventive treatments.
Coauthors of the study at Northwestern include Alexander Misharin, research assistant professor, Shawn Rose, post-doctoral fellow, Angelica Gierut, post-doctoral fellow. Other coauthors include Kenneth Haines III, associate professor of pathology at Yale School of Medicine, and Richard Hotchkiss, professor of anesthesiology, medicine and surgery at Washington University.
###
The study was funded by the following National Institutes of Health grants: AR07611, AR050250 and AR054796 from the National Institute for Arthritis and Musculoskeletal and Skin Diseases, NIH Loan Repayment grants GM044118 and 055194 from the National Institute of General Medical Sciences; AI092490 from the National Institute for Allergy and Infectious Disease, HL108795 from the National Heart Lung and Blood Institute.
'Humanized' mice advance study of rheumatoid arthritis
Human stell cells implanted in mice improve chances of better therapies
2012-10-04
ELSE PRESS RELEASES FROM THIS DATE:
Progress reported in tackling initial, recurrent bouts of health care-associated infection
2012-10-04
CHICAGO — Surgeons are making progress toward preventing initial and recurrent episodes of clostridium difficile colitis (C. difficile or C. diff), a vicious bacterial infection that is estimated to affect about 336,000 people each year, typically patients on antibiotics. Using mouse models, researchers at the Massachusetts General Hospital (MGH), Boston, found that an oral medication may prevent C. difficile infections (CDI). Also, surgeons at Penn State University College of Medicine, Hershey, PA, examined human patients to detect a genetic mutation that could steer ...
New human neurons from adult cells right there in the brain
2012-10-04
VIDEO:
This is a direct observation of neuronal reprogramming of PDGFR-sorted pericyte-derived cells from the adult human brain by continuous live imaging in culture.
Note the change in morphology of a cell...
Click here for more information.
Researchers have discovered a way to generate new human neurons from another type of adult cell found in our brains. The discovery, reported in the October 5th issue of Cell Stem Cell, a Cell Press publication, is one step toward cell-based ...
Newborn mice depend on mom's signature scent
2012-10-04
VIDEO:
For newborn mice to suckle for the very first time and survive, they depend on a signature blend of scents that is unique to their mothers. The findings, published online...
Click here for more information.
For newborn mice to suckle for the very first time and survive, they depend on a signature blend of scents that is unique to their mothers. The findings, published online on October 4 in Current Biology, a Cell Press publication, reveal that mom's natural perfume consists ...
Botox as effective as medication for urinary urgency incontinence
2012-10-04
MAYWOOD – Botox® (onabotulinum toxin-A) injections to the bladder are as effective as medication for treating urinary urgency incontinence in women, but the injection is twice as likely to completely resolve symptoms. These findings were published in the latest issue of The New England Journal of Medicine by a National Institutes of Health clinical trials network including Loyola University Chicago Stritch School of Medicine (SSOM).
Urgency incontinence is urinary incontinence with a strong or sudden need to urinate. Traditionally, this condition has been treated with ...
Clot-busting enzymes are working 2 jobs
2012-10-04
The body's blood clot-busting enzymes are much busier than previously imagined, with new research showing that they also dispose of every cell that dies prematurely from disease or trauma.
In research published today in Cell Reports, scientists from Monash University have demonstrated for the first time the enzyme t-PA, which plays a vital role in the removal of blood clots, is also a major player in the removal of necrotic, or dead, cells.
Necrosis occurs when cells in living tissue die prematurely due to external stress or injury. The body's system for removing waste ...
The smell of Mom: Scientists find elusive trigger of first suckling in mice
2012-10-04
LA JOLLA, CA – A team led by biologists at The Scripps Research Institute has solved the long-standing scientific mystery of how mice first know to nurse or suckle.
This basic mammalian instinct, which could be a key to understanding instinctive behavior more generally, was thought to be triggered by a specific odor (pheromone) that all mouse mothers emit. But, as described online ahead of print by the journal Current Biology on October 4, 2012, the trigger in mice turns out to be a more complicated blend of nature and nurture: a signature mix of odors, unique for each ...
In cancer, an embryonic gene-silencing mechanism gone awry
2012-10-04
There are some genes that are only activated in the very first days of an embryo's existence. Once they have accomplished their task, they are shut down forever, unlike most of our genes, which remain active throughout our lives. EPFL scientists have unveiled part of this strange mechanism. The same process, accidentally initiated later in life, could be responsible for many kinds of cancer. The discovery is described in a recent article in the journal Cell Reports.
The researchers identified a group of proteins that play a key role in this phenomenon. They bind to a ...
BWH researchers discover genetic risk for uterine fibroids
2012-10-04
BOSTON, MA—Uterine fibroids are the most common type of pelvic tumors in women and are the leading cause of hysterectomy in the United States. Researchers from Brigham and Women's Hospital (BWH) are the first to discover a genetic risk allele (an alternative form of a gene) for uterine fibroids in white women using an unbiased, genome-wide approach. This discovery will pave the way for new screening strategies and treatments for uterine fibroids.
The study will be published online on October 4, 2012 in The American Journal of Human Genetics.
The research team, led by ...
Study shows benefits, drawbacks, for women's incontinence treatments
2012-10-04
Oral medication for treating a type of incontinence in women is roughly as effective as Botox injections to the bladder, reported researchers who conducted a National Institutes of Health clinical trials network study, with each form of treatment having benefits and limitations.
After six months, women in both treatment groups said that the average number of daily episodes had declined from about five per day to about 1-2 per day.
In the study, the researchers compared the effectiveness of Botox injections to oral anticholinergic medications for treating urge urinary ...
Babies learn the smell of mum
2012-10-04
Researchers show for the first time that a mammal begins to suckle its mother's milk through a learned response built on learning her unique combination of smells. When it is born, the newborn is exposed to the smell of its mother's amniotic fluid and the baby then responds to those smells to feed.
Prevailing thought has been that pheromones –chemicals that trigger an innate behaviour – drove the suckling response as an automatic behaviour. The new work determines that, in mice, the smells must be learned before the behaviour can occur.
Suckling is a critical step for ...
LAST 30 PRESS RELEASES:
Current antivirals likely less effective against severe infection caused by bird flu virus in cows’ milk
Lassa fever vaccine enters phase 1 clinical trial
Institute for Healthcare Improvement Honors Hebrew SeniorLife’s Orchard Cove and NewBridge on the Charles
Dialing in the temperature needed for precise nuclear timekeeping
Fewer than half of Medicaid managed care plans provide all FDA-approved medications for alcohol use disorder
Mount Sinai researchers specific therapy that teaches patients to tolerate stomach and body discomfort improved functional brain deficits linked to visceral disgust that can cause of food avoidance in
New ACP guideline recommends combination therapy for acute episodic migraines
Last supper of 15-million-year-old freshwater fish
Slow, silent ‘scream’ of epithelial cells detected for first time
How big brains and flexible skulls led to the evolution of modern birds
Iguanas floated one-fifth of the way around the world to colonize Fiji
‘Audible enclaves’ could enable private listening without headphones
Twisting atomically thin materials could advance quantum computers
Impaired gastric myoelectrical rhythms associated with altered autonomic functions in patients with severe ischemic stroke
American College of Cardiology issues concise clinical guidance on evaluation and management of cardiogenic shock
Psychological prehabilitation improves surgical recovery, study finds
Neighborhood dispute among cells: Whichever successfully exerts force wins
Deadline extended for the fifth edition of the SWIM Award for Science Journalism
Unique dove species is the dodo of the Caribbean and in similar danger of dying out
Free University Brussels (VUB) opens its doors to censored American researchers
Neuroanatomy that sets humans apart from other primates
Stress and sex influence traumatic brain injury outcomes
Study: suppressing key protein may unlock immunotherapy for Glioblastoma
Early surgical intervention in children with sleep-disordered breathing reduces need for doctor visits, prescriptions
Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease
Gender-affirming hormone therapy and depressive symptoms among transgender adults
Surgery in kids with mild sleep-disordered breathing tied to fewer doctor visits, meds
Magnetic microalgae on a mission to become robots
Impact journals to participate at the AACR Annual Meeting 2025
Webb telescope captures its first direct images of carbon dioxide outside solar system
[Press-News.org] 'Humanized' mice advance study of rheumatoid arthritisHuman stell cells implanted in mice improve chances of better therapies