(Press-News.org) Autism results from abnormal cell communication. Testing a new theory, researchers at the University of California, San Diego School of Medicine have used a newly discovered function of an old drug to restore cell communications in a mouse model of autism, reversing symptoms of the devastating disorder.
The findings are published in the March 13, 2013 issue of the journal PLOS ONE.
"Our (cell danger) theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function," said Robert Naviaux, MD, PhD, professor of medicine and co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego. "We used a class of drugs that has been around for almost a century to treat other diseases to block the 'danger' signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication."
"Of course, correcting abnormalities in a mouse is a long way from a cure for humans," said Naviaux, "but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach – called antipurinergic therapy or APT – offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism."
Autism spectrum disorders (ASDs) are complex disorders defined by abnormalities in the development of language, social and repetitive behaviors. Hundreds of different genetic and environment factors are known to confer risk. In this study, nearly a dozen UC San Diego scientists from different disciplines collaborated to find a unifying mechanism that explains autism. Their work is the result of one of just three international "Trailblazer" awards given by the group Autism Speaks in 2011.
Describing a completely new theory for the origin and treatment of autism using APT, Naviaux and colleagues introduce the concept that a large majority of both genetic and environmental causes for autism act by producing a sustained cell danger response – the metabolic state underlying innate immunity and inflammation.
"When cells are exposed to classical forms of dangers, such as a virus, infection or toxic environmental substance, a defense mechanism is activated," Naviaux explained. "This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking."
Since mitochondria – the so-called "power plants" of the cell – play a central role in both infectious and non-infectious cellular stress, innate immunity and inflammation, Naviaux and colleagues searched for a signaling system in the body that was both linked to mitochondria and critical for innate immunity. They found it in extracellular nucleotides like adenosine triphosphate (ATP) and other mitokines – signaling molecules made by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body. Fifteen types of purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism.
The researchers tested suramin – a well-known inhibitor of purinergic signaling used medically for the treatment of African sleeping sickness since shortly after it was synthesized in 1916 – in mice. They found that this APT mediator corrected autism-like symptoms in the animal model, even if the treatment was started well after the onset of symptoms. The drug restored 17 types of multi-symptom abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination and normalizing mitochondrial metabolism.
"The striking effectiveness shown in this study using APT to 'reprogram' the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders," Naviaux said.
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Additional contributors to the study include Zarazuela Zolkipli, Lin Wang, Tomohiro Nakayama, Jane C. Naviaux, Thuy P. Le, Michael Schuchbauer, Mihael Rogac, Qingbo Tang, Laura L. Dugan, and Susan B. Powell.
Funding for the project was provided by Autism Speaks, the UCSD Christini Fund, the Jane Botsford-Johnson Foundation, the Wright Family Foundation, the Lennox Foundation, the Larry L. Hillblom Foundation, the Gerber Foundation, and Hailey's Wish Foundation.
Some of the brightest galaxies in the universe – infant galaxies that churned out tens of thousands of stars each year at the dawn of the universe – evolved much sooner and in greater numbers than previously thought, according to new measurements obtained by University of Arizona astronomers.
The results are published in a set of papers to appear in the journal Nature on March 14 and in the Astrophysical Journal. The research is the most recent example of the discoveries coming from the new international ALMA observatory, which celebrates its inauguration today. ALMA, ...
ORLANDO, Fla., March 13, 2013 – Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have determined the complete three-dimensional structure of a protein called HNF-4α. HNF-4α controls gene expression in the liver and pancreas, switching genes on or off as needed. People with mature onset diabetes of the young (MODY1), a rare form of the disease, have inherited mutations in the HNF-4α protein. This first-ever look at HNF-4α's full structure, published March 13 in Nature, uncovers new information about how it functions. The study ...
NEW YORK, MARCH 13, 2013 – Researchers have discovered a unique monoclonal antibody that can effectively reach inside a cancer cell, a key goal for these important anticancer agents, since most proteins that cause cancer or are associated with cancer are buried inside cancer cells. Scientists from Memorial Sloan-Kettering Cancer Center and Eureka Therapeutics have collaborated to create the new human monoclonal antibody, which targets a protein associated with many types of cancer and is of great interest to cancer researchers.
Unlike other human therapeutic monoclonal ...
When a batch of bright cosmic objects first appeared in maps in 2008 made with data from the South Pole Telescope, astronomers at the University of Chicago's Kavli Institute for Cosmological Physics regarded it only as an unavoidable nuisance.
The light sources interfered with efforts to measure more precisely the cosmic microwave background—the afterglow of the big bang. But the astronomers soon realized that they had made a rare find in South Pole Telescope's large survey of the sky. The spectra of some of the bright objects, which is the rainbow of light they emit, ...
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"I wouldn't call the results surprising," said Meredith Evans Wagner, a visiting scholar from the University of Florida in the Center for Systems Integration and Sustainability (CSIS) at Michigan State University and part of the research team. "Other research has shown that people and carnivores can coexist, ...
PASADENA, Calif.—Galaxies have been experiencing vigorous bursts of star formation from much earlier in cosmic history than previously thought, according to new observations by a Caltech-led team.
These so-called starburst galaxies produce stars at a prodigious rate—creating the equivalent of a thousand new suns per year. Now the astronomers have found starbursts that were churning out stars when the universe was just a billion years old. Previously, astronomers didn't know whether galaxies could form stars at such high rates so early in time.
The discovery enables ...
Colonoscopy is one of the most effective cancer screening procedures available. Colon cancer grows very slowly and can be treated if caught early through screening. But, perhaps because of this success, older Americans are undergoing screening colonoscopies despite recommendations against screening in adults aged 76 and older.
A new study by researchers at the University of Texas Medical Branch at Galveston published online today in JAMA Internal Medicine shows that one out of four colonoscopies paid for by Medicare is potentially inappropriate under current screening ...
MADISON, Wis., March 13, 2013 – Even after researchers studying White Nose Syndrome (WNS) established that a fungus called Geomyces destructans is at the heart of the devastating disease, detecting it depended largely on finding dead or dying bats.
This month, the journal Mycologia will publish research by a team of U.S. Forest Service scientists and partners identifying additional species of Geomyces and describing development of a highly sensitive DNA-based technique for early identification of Geomyces destructans on bats as well as in soils and on cave walls.
"The ...
CHAMPAIGN, Ill. — A little-noticed provision of the Affordable Care Act requires all chain restaurants and retail food establishments with 20 or more locations to list calorie counts on their menus. But according to research co-written by a University of Illinois agricultural economist, numeric calorie labels might not be the most effective way to influence patrons to select "healthier" (often interpreted as lower-calorie) items.
Brenna Ellison, a professor of agricultural and consumer economics, says placing a symbolic label in addition to the numeric calorie information ...
NASA's Tropical Rainfall Measuring Mission satellite, also known as TRMM, flew over Cyclone Sandra twice in one day and noticed a large decrease in rainfall intensity over a nine hour period.
On March 11, 2013, NASA's TRMM satellite twice flew above weakening tropical cyclone Sandra as it was passing to the west of New Caledonia in the southern Pacific Ocean. TRMM's Precipitation Radar (PR) had a very good view of Sandra as it passed directly above the tropical cyclone on March 11 at 1312 UTC (9:12 a.m. EST). TRMM PR measured rainfall at the extreme rate of over 206 mm ...
