PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Single dose reverses autism-like symptoms in mice

Old drug used for sleeping sickness may point to new treatment in humans

Single dose reverses autism-like symptoms in mice
2014-06-17
(Press-News.org) In a further test of a novel theory that suggests autism is the consequence of abnormal cell communication, researchers at the University of California, San Diego School of Medicine report that an almost century-old drug approved for treating sleeping sickness also restores normal cellular signaling in a mouse model of autism, reversing symptoms of the neurological disorder in animals that were the human biological age equivalent of 30 years old.

The findings, published in the June 17, 2014 online issue of Translational Psychiatry, follow up on similar research published last year by senior author Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology, and colleagues.

Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: "Twenty percent of the known factors associated with autism are genetic, but most are not. It's wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact. The net result of this interaction is metabolism."

Naviaux, who is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, said one of the universal symptoms of autism is metabolic disturbances. "Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them. These create a sort of chemical glow that broadcasts the state of health of the cell."

Cells threatened or damaged by microbes, such as viruses or bacteria, or by physical forces or by chemicals, such as pollutants, react defensively, a part of the normal immune response, Naviaux said. Their membranes stiffen. Internal metabolic processes are altered, most notably mitochondria – the cells' critical "power plants." And communications between cells are dramatically reduced. This is the "cell danger response," said Naviaux, and if it persists, the result can be lasting, diverse impairment. If it occurs during childhood, for example, neurodevelopment is delayed.

"Cells behave like countries at war," said Naviaux. "When a threat begins, they harden their borders. They don't trust their neighbors. But without constant communication with the outside, cells begin to function differently. In the case of neurons, it might be by making fewer or too many connections. One way to look at this related to autism is this: When cells stop talking to each other, children stop talking."

Naviaux and colleagues have focused on a cellular signaling system linked to both mitochondrial function and to the cell's innate immune function. Specifically, they have zeroed in on the role of nucleotides like adenosine triphosphate (ATP) and other signaling mitokines – molecules generated 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. Nineteen types of so-called 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, such as impaired language and social skills.

In their latest work, Naviaux again tested the effect of suramin, a well-known inhibitor of purinergic signaling that was first synthesized in 1916 and is used to treat trypanosomiasis or African sleeping sickness, a parasitic disease. They found that suramin blocked the extracellular signaling pathway used by ATP and other mitokines in a mouse model of autism spectrum disorder (ASD), ending the cell danger response and related inflammation. Cells subsequently began behaving normally and autism-like behaviors and metabolism in the mice were corrected.

However, the biological and behavioral benefits of suramin were not permanent, nor preventive. A single dose remained effective in the mice for about five weeks, and then washed out. Moreover, suramin cannot be taken long-term since it can result in anemia and adrenal gland dysfunction.

Still, Naviaux said these and earlier findings are sufficiently encouraging to soon launch a small phase 1 clinical trial with children who have ASD. He expects the trial to begin later this year.

"Obviously correcting abnormalities in a mouse is a long way from a cure in humans, but we think this approach – antipurinergic therapy – is a new and fresh way to think about and address the challenge of autism.

"Our work doesn't contradict what others have discovered or done. It's another perspective. Our idea is that this kind of treatment – eliminating a basic, underlying metabolic dysfunction – removes a hurdle that might make other non-drug behavioral and developmental therapies of autism more effective. The discovery that a single dose of medicine can fundamentally reset metabolism for weeks means that newer and safer drugs might not need to be given chronically. Members of this new class of medicines might need to be given only intermittently during sensitive developmental windows to unblock metabolism and permit improved development in response to many kinds of behavioral and occupational therapies, and to natural play."

INFORMATION: Co-authors are Jane C. Naviaux, Michael A. Schuchbauer and Susan B. Powell of the UCSD Department of Psychiatry; Kefeng Li and Lin Wang, UCSD Mitochondrial and Metabolic Disease Center and UCSD Department of Medicine; and Victoria B. Risbrough, UCSD Department of Psychiatry and San Diego Veterans Affairs Center for Excellence in Stress and Mental Health.

Funding for this research came, in part, from the Jane Botsford Johnson Foundation, the National Institutes of Health (grant MH091407), the UCSD Christini Fund, the Wright Family Foundation and the It Takes Guts Foundation.


[Attachments] See images for this press release:
Single dose reverses autism-like symptoms in mice

ELSE PRESS RELEASES FROM THIS DATE:

Breast cancer diagnosis, mammography improved by considering patient risk: INFORMS paper

2014-06-17
A new approach to examining mammograms that takes into account a woman's health risk profile would reduce the number of cancer instances missed and also cut the number of false positives, according to a paper being presented at a conference of the Institute for Operations Research and the Management Sciences (INFORMS). Mehmet U.S. Ayvaci of the University of Texas Dallas will present his research group's findings about the role of risk profiling in the interpretation of mammograms at Advances in Decision Analysis, a conference sponsored by the INFORMS Decision Analysis ...

Boost for dopamine packaging protects brain in Parkinson's model

2014-06-17
Researchers from Emory's Rollins School of Public Health discovered that an increase in the protein that helps store dopamine, a critical brain chemical, led to enhanced dopamine neurotransmission and protection from a Parkinson's disease-related neurotoxin in mice. Dopamine and related neurotransmitters are stored in small storage packages called vesicles by the vesicular monoamine transporter (VMAT2). When released from these packages dopamine can help regulate movement, pleasure, and emotional response. Low dopamine levels are associated with neurodegenerative diseases ...

Gut bacteria predict survival after stem cell transplant, study shows

2014-06-17
(WASHINGTON, June 17, 2014) – New research, published online today in Blood, the Journal of the American Society of Hematology, suggests that the diversity of bacteria in the gastrointestinal tract of patients receiving stem cell transplants may be an important predictor of their post-transplant survival. A healthy gastrointestinal tract contains a balanced community of microorganisms (known as microbiota), largely comprised of "friendly" bacteria that aid digestion and are important to immune system function. When this community of microbes is compromised, the microbiota ...

Ice cream chemistry: The inside scoop on a classic summer treat (video)

Ice cream chemistry: The inside scoop on a classic summer treat (video)
2014-06-17
WASHINGTON, June 17, 2014 — The summer weather is here, and if you've been out in the sun, you're probably craving some ice cream to cool off. In the American Chemical Society's latest Reactions video, American University Assistant Professor Matt Hartings, Ph.D., breaks down the chemistry of this favorite frozen treat, including what makes ice cream creamy or crunchy, and why it is so sweet. The video is available at http://youtu.be/-rlapUkWCSM INFORMATION: Subscribe to the series at Reactions YouTube, and follow us on Twitter @ACSreactions to be the first to see our ...

Climate change deflecting attention from biodiversity loss

2014-06-17
New research from the University of Kent suggests that recent high levels of media coverage for climate change may have deflected attention and funding from biodiversity loss. In a paper published by the journal Bioscience, Kent conservationists also recommend that, to prevent biodiversity from becoming a declining priority, conservationists need to leverage the importance of climate change to obtain more funds and draw attention to other research areas such as biodiversity conservation. For the study, the team conducted a content analysis of newspaper coverage in ...

Crowdsourcing the phase problem

Crowdsourcing the phase problem
2014-06-17
Compared with humans, computers have the capacity to solve problems at much greater speed. There are many problems, however, where computational speed alone is insufficient to find a correct or optimal solution, for example because the parameter "space" cannot be fully searched in a practical time. In contrast, the human mind can formulate expert knowledge specific for particular problems, providing a capacity to guide more efficient searches, although with more limited processing speed. The power of the human contribution can be multiplied through the efforts of a greater ...

Genetic pathway can slow spread of ovarian cancer

2014-06-17
University of Adelaide research into the origins of ovarian cancer has led to the discovery of a genetic pathway that could slow the spread of the cancer. The discovery is in part due to research into the genetics of humans' most distant mammalian relative, the platypus. In a paper published today in the journal PLOS ONE, researchers characterize a genetic pathway – involving piRNA genes – that is turned on in ovarian cancer. "This pathway is important for the development of the ovaries in drosophila flies but little is known about its role in the mammalian ovary," ...

NIST technique could make sub-wavelength images at radio frequencies

NIST technique could make sub-wavelength images at radio frequencies
2014-06-17
Imaging and mapping of electric fields at radio frequencies (RF)* currently requires the use of metallic structures such as dipoles, probes and reference antennas. To make such measurements efficiently, the size of these structures needs to be on the order of the wavelength of the RF fields to be mapped. This poses practical limitations on the smallest features that can be measured. New theoretical and experimental work by researchers at the National Institute of Standards and Technology (NIST) and the University of Michigan suggests an innovative method to overcome ...

Overweight + gene mutation = elevated liver values in children

2014-06-17
A study carried out at the Institute of Biomedicine of the University of Eastern Finland shows that a common mutation in the PNPLA3 gene combined with overweight results in elevated ALAT values in children. The ALAT value is an indicator of liver metabolism. In adults, this gene mutation is known to promote the accumulation of fat in the liver. The new results indicate that a healthy lifestyle is important already in childhood in order to prevent the accumulation of fat in the liver, and it is especially important for those carrying the risk gene. The results will be published ...

Brazilian surgeons review experience with soccer-related facial fractures for PRS-GO

2014-06-17
June 17,2014- Fractures of the nose and other facial bones are a relatively common and potentially serious injury in soccer players, reports a Brazilian study in Plastic and Reconstructive Surgery—Global Open® , the official open-access medical journal of the American Society of Plastic Surgeons (ASPS). On the eve of the 2014 World Cup, a group of Brazilian plastic surgeons review their experience with soccer-related facial fractures requiring surgery. Dr. Dov Charles Goldenberg, MD, PhD, of University of São Paulo and colleagues write, "Due to exposure and the lack ...

LAST 30 PRESS RELEASES:

Exercise as an anti-ageing intervention to avoid detrimental impact of mental fatigue

UMass Amherst Nursing Professor Emerita honored as ‘Living Legend’

New guidelines aim to improve cystic fibrosis screening

Picky eaters by day, buffet by night: Butterfly, moth diets sync to plant aromas

Pennington Biomedical’s Dr. Leanne Redman honored with the E. V. McCollum Award from the American Society for Nutrition

CCNY physicists uncover electronic interactions mediated via spin waves

Researchers’ 3D-printing formula may transform future of foam

Nurture more important than nature for robotic hand

Drug-delivering aptamers target leukemia stem cells for one-two knockout punch

New study finds that over 95% of sponsored influencer posts on Twitter were not disclosed

New sea grant report helps great lakes fish farmers navigate aquaculture regulations

Strain “trick” improves perovskite solar cells’ efficiency

How GPS helps older drivers stay on the roads

Estrogen and progesterone stimulate the body to make opioids

Dancing with the cells – how acoustically levitating a diamond led to a breakthrough in biotech automation

Machine learning helps construct an evolutionary timeline of bacteria

Cellular regulator of mRNA vaccine revealed... offering new therapeutic options

Animal behavioral diversity at risk in the face of declining biodiversity

Finding their way: GPS ignites independence in older adult drivers

Antibiotic resistance among key bacterial species plateaus over time

‘Some insects are declining but what’s happening to the other 99%?’

Powerful new software platform could reshape biomedical research by making data analysis more accessible

Revealing capillaries and cells in living organs with ultrasound

American College of Physicians awards $260,000 in grants to address equity challenges in obesity care

Researchers from MARE ULisboa discover that the European catfish, an invasive species in Portugal, has a prolonged breeding season, enhancing its invasive potential

Rakesh K. Jain, PhD, FAACR, honored with the 2025 AACR Award for Lifetime Achievement in Cancer Research

Solar cells made of moon dust could power future space exploration

Deporting immigrants may further shrink the health care workforce

Border region emergency medical services in migrant emergency care

Resident physician intentions regarding unionization

[Press-News.org] Single dose reverses autism-like symptoms in mice
Old drug used for sleeping sickness may point to new treatment in humans