“Research aimed at improving early detection of autism has largely focused on measurement of social and communication development,” said Dr. Rebecca Landa, study author and director of the Center for Autism and Related Disorders at Kennedy Krieger Institute. “However, disruption in early motor development may also provide important clues about developmental disorders such as autism.”

On May 17 in Toronto, Dr. Landa will present this and other new research on motor delay and how it impacts development of language and social skills. The spring International Meeting for Autism Research is an annual scientific meeting providing international researchers with an opportunity to share their findings on ASD.

Before Dr. Landa’s current study, the head-lag text has not been used to diagnose ASD. Her team assessed infants in a “pull-to-sit” task, a simple measure of postural control in infants. Typically developing infants achieve this type of postural control by four months of age.

Dr. Landa’s team studied two groups of infants. The first group consisted of 40 infants, ages 5.6 to 10 months, considered to be at high genetic risk because a sibling had autism. Dr. Landa and her team examined their ability to maintain head alignment when being carefully, yet firmly, pulled by the arms from lying flat on his/her back to a sitting position. Infants were scored according to whether their head maintained alignment with the spine, or was in front of the spine, during the task. Lack of this head control indicated head lag.

The second group examined six-month-olds at a single point in time for the presence of head lag. Dr. Landa and her team found that 75% (n =15) of high-risk infants exhibited head lag, compared to 33% (n =7) of low-risk infants, further supporting that head lag is more likely in infants at risk of developing ASD. “Our findings show that the evaluation of motor skills should be incorporated with other behavioral assessments to yield insights into the very earliest signs of autism,” said Dr. Landa.

“While previous research shows that motor impairments are linked to social and communication deficits in older children with autism, the field is just starting to examine this in younger children,” said Dr. Landa. “Our initial research suggests that motor delays may have an important impact on child development.”

Building on the head lag research, Dr. Landa’s team conducted a separate longitudinal study with 14-, 24- and 36-month-old children at high and low risk of developing ASD. The study found that motor delay becomes increasingly evident as children with ASD near their third birthday, yet not all children with ASD experience motor delay. Results showed that children with ASD who experience motor delays are more severely impaired by three years of age than children with ASD with no motor delays.

“While more research is needed to examine why not all children with ASD experience motor delay, the results of our studies examining motor development add to the body of research demonstrating that early detection and intervention for infants later diagnosed with autism is possible and remains crucial to minimize delays and improve outcomes,” said Dr. Landa.

To reach Dr. Landa’s team at the Kennedy Krieger Institute follow this LINK.

ICare4Autism Founder and President, Joshua Weinstein with Dr. W. Ted Brown

The Fragile X Syndrome is the most common inherited cause of intellectual disability. Fragile X has a population incidence of approximately 1 in 4,000 affected (full-mutation) males, 1 in 6,000 affected females, 1 in 700 premutation carrier males and 1 in 260 carrier females. This disorder typically causes moderate to severe intellectual deficiency in affected males, and milder deficiency in affected females.  It is associated with autism or PDD-NOS in about 50% of affected males, and most affected individuals evidence some autistic-like behaviors. 

Fragile X syndrome is considered to be the most common known single gene cause of autism. It is estimated that Fragile X accounts for 2-4% of intellectual deficiency overall, and is second to Down syndrome, which is not inherited, as a genetic cause of intellectual deficiency. The fragile X mutation results in the lack of expression of the Fragile X Protein (FMRP), an mRNA finding protein, which results in overexpression of the glutamate (stimulatory) and under-expression of the GABA (inhibitory) pathways in the brain.

Current experimental treatment trails are being carried out in Fragile X and in autism with glutamate receptor blockers and GABA stimulatory drugs.  The underlying defects in neurochemical pathways in both conditions appear to have much in common, involving the ERK, mTOR and PI3K signaling pathways.

Dr. W. Ted Brown will be speaking at the upcoming ICare4Autism International Conference on Autism, in Israel, about the relationship between Fragile X syndrome and autism.

W. Ted Brown, MD, PhD, is the Director of the New York State Institute for Basic Research (IBR) in Developmental Disabilities, Chair of the IBR Department of Human Genetics and Director of the IBR Jervis Clinic.  He is a fellow of the American College of Medical Genetics and Professor at the State University of New York- Downstate Medical Center in Brooklyn.

In 1991, he was appointed the Director of IBR’s Jervis Clinic and in 2005 became IBR’s Director. He is the author of more than 350 publications.  At IBR, he began research focused on the Fragile X syndrome, which was then newly recognized and is now considered to be the most common inherited cause of intellectual deficiency or mental retardation. At IBR, he established a DNA diagnostic and molecular laboratory. He developed a screening and prenatal testing program for Fragile X.

His work on Fragile X has ranged from clinical studies relating to phenotype, to family inheritance studies, to mouse model development, and to basic molecular research. His current research is focused on autism genetics and the Fragile X syndrome.

Eyal Ben-David and Sagiv Shifman, Hebrew University of Jerusalem

It is widely understood that different genes interact with environmental factors to influence autism, but new research finds a common ground as the various genes involved in autism appear to influence special processes in the brain.

Autism is influenced by many different genes, and different genes are involved in different individuals, making it hard to find the common genetic ground between patients.

Now, research conducted at the Hebrew University of Jerusalem has shown that the different genes involved in autism tend to be involved in specific processes in the brain. This can explain similarities in the behavioral symptoms of different people with autism, but also the large spectrum of behaviors observed in different individuals with autism.

The Hebrew University research, conducted by Dr. Sagiv Shifman and his doctoral student Eyal Ben-David of the Department of Genetics at the Alexander Silberman Institute of Life Sciences, has potential implications for early diagnosis as well as for treatment of autism in the future.

Dr. Shifman’s areas of interest are the genetics of schizophrenia and autism and genetics of variation in gene expression.  He will be speaking about this research “Shared neuronal pathways affected by common and rare variants in autism spectrum disorders” at ICare4Autism’s upcoming International Autism Conference in Jerusalem.

The mission of the Hebrew University project was to test the contribution of rare genetic mutations, as well as the genetic variations which are common in the population, and to see whether these different types of genetic risk factors are related. Instead of testing individual genes, the researchers chose to study gene collections, in an attempt to understand general pathways involved in autism.

Based on genetic data from thousands of families with autistic children, the researchers studied the contribution of different groups of genes to autism.

To their surprise, they found – when looking at mutations found in autism as well as thousands of common gene variants that are more frequently seen in individuals with autism – that these mutations and variations are located in specific functional groups.

When looking at families with one individual with autism (sporadic cases), and in families where there is more than one affected individual (multiplex cases), the same variants were seen acting in both cases. These groups of genes are highly active in the first year of life, and are involved in processes of learning, memory, and sensory perception.

The Hebrew University scientists believe that their work could pave the way for large-scale genetic scans in the future that could allow for early diagnosis of autism. Further, the results of their study provide a ray of hope that by concentrating on specific gene groups, it will one day be possible to design drugs which could alleviate symptom

Ben-David E, Shifman S (2012) Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders. PLoS Genet 8(3):e1002556. doi:10.1371/journal.pgen.1002556

http://medicalxpress.com/news/2012-05-genetic-disrupted-autistic-brain.html

The study, led by Gladstone Investigator Jorge J. Palop, PhD, revealed that low levels of a protein, called Nav1.1, disrupt the electrical activity between brain cells. Such activity is crucial for healthy brain function and memory. Indeed, the researchers found that restoring Nav1.1 levels in mice that were genetically modified to mimic key aspects of Alzheimer’s disease (AD-mice) improved learning and memory functions and increased their lifespan.

“It is estimated that more than 30 million people worldwide suffer from Alzheimer’s disease and that number is expected to rise dramatically in the near future,” said Lennart Mucke, MD, who directs neurological research at Gladstone, an independent and nonprofit biomedical-research organization. “This research improves our understanding of the biological processes that underlie cognitive dysfunction in this disease and could open the door for new therapeutic interventions.”

In the brain, neurons form highly interconnected networks, using chemical and electrical signals to communicate with each other. The researchers investigated whether this communication between neurons is disrupted in AD-mice, and if so, how this may affect the symptoms of Alzheimer’s disease.

“Like a conductor in an orchestra, PV cells regulate brain rhythms by precisely controlling excitatory brain activity,” said Laure Verret, PhD, postdoctoral fellow and lead author. “We found that PV cells in patients with Alzheimer’s and in AD-mice have low levels of the protein Nav1.1 – likely contributing to PV cell dysfunction. As a consequence, AD-mice had abnormal brain rhythms. By restoring Nav1.1 levels, we were able to re-establish normal brain function.”

Indeed, the scientists found that increasing Nav1.1 levels in PV cells improves brain wave activity, learning, memory and survival rates in AD-mice.

“Enhancing Nav1.1 activity, and consequently improving PV cell function, may help in the treatment of Alzheimer’s disease and other neurological disorders associated with gamma-wave alterations and cognitive impairments such as epilepsy, autism and schizophrenia,” said Dr. Palop, who is also an assistant professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. “These findings may allow us to develop therapies to help patients with these devastating diseases.”

Gladstone Institutes. (2012, April 29). “Mechanism May Aid Treatment For Alzheimer’s And Neurological Disorders Associated With Gamma-Wave Alterations And Cognitive Impairments.“ Medical News Today. Retrieved from http://www.medicalnewstoday.com/releases/244665.php.

Verret, Laure; Mann, Edward O.; Hang, Giao B.; Barth, Albert M.I.; Cobos, Inma; Ho, Kaitlyn; Devidze, Nino; Masliah, Eliezer; Kreitzer, Anatol C.; Mody, Istvan; Mucke, Lennart; Palop, Jorge J. Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model.  Cell doi:10.1016/j.cell.2012.02.046 (volume 149 issue 3 pp.708 – 721)

Young brains are capable of forming many new synapses, and are consequently better at learning new things. That is why we acquire vital skills – walking, talking, hearing and seeing – early on in life. The adult brain stabilizes the synapses so that we can use what we have learned in childhood for the rest of our lives. 

Earlier research found that approximately one fifth of the synapses in the brain inhibit rather than excite other nerve-cell activity. Neuroscientists have now shown that many of these inhibitory synapses vanish if the adult brain is forced to learn new skills. They came to this conclusion by labeling inhibitory synapses in mouse brains with fluorescent proteins and then tracking them for several weeks using a specialized microscope. They then closed one of the mice’s eyes temporarily to accustom them to seeing through just one eye. After a few days, the area of the brain that processes information from both eyes began to respond more actively to the open eye. At the same time, many of the inhibitory synapses disappeared and were later replaced by new synapses.

Inhibitory synapses are essential for the way networks function in the brain. “Think of the excitatory synapses as a road network, with traffic being guided from A to B, and the inhibitory synapses as the matrix signs that regulate the traffic,” explains research leader Christiaan Levelt. “The inhibitory synapses ensure an efficient flow of traffic in the brain. If they don’t, the system becomes overloaded, for example as in epilepsy; if they constantly indicate a speed of 20 kilometres an hour, then everything will grind to a halt, for example when an anaesthetic is administered. If you can move the signs to different locations, you can bring about major changes in traffic flows without having to entirely reroute the road network.”

Inhibitory synapses play a immensely influential role on learning in the young brain. People who have neurodevelopmental disorders – including autism – may have trouble forming inhibitory synapses. The discovery that the adult brain is still capable of pruning or forming these synapses offers hope that pharmacological or genetic intervention can be used to manage this process. This could lead to important guideposts for treating autism, but also repairing damaged brain tissue.

Daniëlle van Versendaal, Rajeev Rajendran, M. Hadi Saiepour, Jan Klooster, Laura Smit-Rigter, Jean-Pierre Sommeijer, Chris I. De Zeeuw, Sonja B. Hofer, J. Alexander Heimel, Christiaan N. Levelt. Elimination of Inhibitory Synapses Is a Major Component of Adult Ocular Dominance Plasticity. Neuron, 2012; 74 (2): 374 DOI:10.1016/j.neuron.2012.03.015

Royal Netherlands Academy of Arts and Sciences. (2012, April 30). “Learning Mechanism Of The Adult Brain Revealed.” Medical News Today. Retrieved from http://www.medicalnewstoday.com/releases/244690.php.

Attendees at past ICare4Autism International Autism Conference

On August 1-2, 2012, more than 1,500 leaders in autism research, educationand policy from every continent will gather in Jerusalem, Israel, for ICare4Autism‘s 2012 International Conference, “Autism: A Global Perspective“.

Dr.Joshua Weinstein, CEO & Founder indicated that the, “Conference will highlight groundbreaking research into the causes and treatments of Autism Spectrum Disorders, and serve as a catalyst for powerful new collaborations to tackle the global autism crisis”.

Students from around the world are invited to present their autism research at a poster session. One poster will be selected by the review committee to receive a scholarship to attend the Conference.  The scholarship will cover travel, hotel accommodations and conference registration fee. The scholarship winner will also be invited to participate on one of the Conference panels. The Poster Session consists of physical displays (aka posters) of information shown during a 60-90 minute session, with presenters standing by their poster reporting empirical research and pilot projects for future research.  Attendees have the opportunity to speak with the presenters about their work.

Dame Stephanie Shirley, The British Government’s Founding Ambassador for Philanthropy, and Chairman of the Shirley Foundation, will deliver the Keynote Address and The First Lady of Panama Mrs. Marta Linares de Martinelli will be giving opening remarks.

They will be joined by distinguished researchers and practitioners from more than 20 countries who will unveil their latest biomedical discoveries andeducational innovations.

Groundbreaking biomedical research will be presented; notably Henry Markram, Ph.D, the Director of Blue Brain Project, Coordinator of the Human Brain Project and Professor at Swiss Federal Institute for Technology (EPFL) will present, “Prospects of using detailed brain simulations to explore possible causes and treatments of Autism”

Innovativeeducational practices will be featured in presentations by Dr. S. Mariam Aljunied (Senior Autism Specialist, Singapore Ministry of Education); Dr.Carlos MarcinSalazar (Director of the National Autism Clinic of Mexico); and Dr. Pamela Wolfberg (Director, Autism Spectrum Program,UniversityofCalifornia San Francisco). Attendees will tour the campus where ICare4Autism will open the world’s first Global Autism Research andEducationCenterin 2015.

ICare4Autism (InternationalCenterfor Autism Research & Education) is a charitable organization, founded in 2004 to catalyze breakthrough innovations in autism research, diagnosis and treatment.

Martha Naber, education program coordinator at KVCC, said the program is important for the health of families and communities.

As the prevalence of Autism rises, so does the need for educators to have a thorough understanding of those autism spectrum disorders.  Naber said the courses will be helpful for a host of people, including education technicians, teachers in search of recertification credits, health-care workers and family members.

“Each person on the spectrum is unique,” she said. “There is no one method (of teaching). One (child) might be very verbal and one might not have any language. One might flap their arms and one might not at all. One might be highly sensitive to light and another might be sensitive to sounds.”

Courses in the college’s 62-credit program include Working with Family Members, Language Development, Data Collection, and Assisted Technology.

Kennebec Valley Community College President Barbara Woodlee said the college is reacting to the needs of the community.

“KVCC has always adapted its program offerings to meet changing workforce needs, and the addition of a two-year autism degree is both timely and appropriate given the college’s experience in autism education and the significant increase in autism diagnosis nationwide,” she said.

Two courses for the degree will be offered this summer, according to Jonathan Humphrey, media specialist at the college. One will be available statewide through interactive television sites and one will be available online.

Researchers Martin Knapp, Ph.D., of the London School of Economics, and David Mandell, Sc.D., of the University of Pennsylvania, compiled information from recent studies of autism costs from many sources to determine the current cost of autism associated with the previous CDC-reported prevalence that 1:110 children were diagnosed with an autism spectrum disorder (ASD).  The prevalence has now increased to 1:88 and as high as 1:54 in boys. The cost of autism continues to grow with the rise in prevalence. The research team found that the cost of autism in the U.S. alone is greater than the entire Gross Domestic Product (GDP) of 139 countries around the world.

“The need for action has never been more urgent.” said Dr. Joshua Weinstein, CEO & Founder of Shema Kolainu - Hear Our Voices in Brooklyn, NY and ICare4Autism in Jerusalem, Israel   “The soaring autism rate is one of our major concerns and one that I have been trying to alarm the world for many years. That is why I am convening the International Autism Conference in August that will take place in Jerusalem”

This research also found that intellectual disability plays a key role in the cost of autism to individuals, families, and society as a whole. The costs of autism per year are nearly twice as high on average for children and adults with intellectual disability than for children and adults without intellectual disability, $2.3 million in the U.S. and £1.5 million in the U.K. ($2.4 million) for those individuals who are impacted by intellectual disability compared with more than $1.4 million in the U.S. and £917,000 ($1.46 million) in the U.K. for those who do not have intellectual disability.  The latest CDC report found that in the U.S. the majority (62%) of those with ASDs did not have intellectual disability.

Experts consistently point to early interventions as key to increasing language and IQ scores, and reducing life span costs.

“We have entered a new age of autism, characterized on the one hand by unprecedented incidence, and on the other by advanced research, earlier diagnosis, and progressively more effective intervention.”  Dr Weinstein adds.

Those with autism often have an increased ability to concentrate on one task and can have very focused areas of interest.  There is a body of research that shows that these individuals can be more sensitive to other stimuli, often unable to ‘filter out’ irrelevant stimuli, such as flashing lights or particular sounds.

Professor Nilli Lavie, from the Institute of Cognitive Neuroscience at UCL, hypothesizes that this combination of the ability to focus and a vulnerability to distraction might be the result of a higher than normal information processing capacity.

“Our work on perceptual capacity in the typical adult brain suggests a clear explanation for the unique cognitive profile that people with autism show,” she says.

Professor Lavie, together with Dr Anna Remington and Dr John Swettenham from the UCL Developmental Science department, tested this theory on 16 adult volunteers with autism spectrum disorders and compared their results against those of 16 typical adults in a task to challenge their perceptual load capacity.

The task involved looking at a circle of letters flashed very briefly on the screen and searching for some ‘target’ letters. Participants were asked to simultaneously detect a small grey shape that occasionally appeared outside the letter circle.

When only one or two letters were flashed on the screen, the researchers found that both groups could successfully find the letter and detect the shape. However, as the number of letters increased, thus increasing the difficulty, the detection performance of the typical adults was impaired — but not of the adults with autism spectrum disorders, who were able to detect the extra shape just as well in the more challenging conditions. When the task became harder, they significantly outperformed the typical adults.

Professor Lavie says: “Our study confirms our hypothesis that people with autism have higher perceptual capacity compared to the typical population. This can only be seen once the task becomes more demanding, with more information to process. In the more challenging task conditions, people with autism are able to perceive significantly more information than the typical adult.”

Professor Lavie believes that the finding may help explain why people with autism spectrum disorders, such as Asperger’s syndrome, may excel in some careers such as IT, which can require intense concentration and the ability to process a great deal of information from a computer screen.

Dr. Stephen Shore, Assistant Professor at Adelphi University, a published author on autism believes that the key to finding successful employment for those with autism is through exploiting their natural strengths and interests.

“There are clearly careers, such as in IT, that can benefit from employing people with high-functioning autism spectrum disorders.” says Professor Lavie.

Dr, Joshua Weinstein, CEO and Founder of ICare4Autism, has initiated the autism workforce development initiative, as part of the Global Autism Center on Mt Scopus. It will have a special targeted program to place persons with Asperger’s Syndrome and other high functioning individuals in technology sector jobs.  This initiative will offer unique opportunities to Israelis with autism, their families and – by creating new high value-added private sector opportunities – the entire community.  By creating an urgently needed replicable model, it will also have a global reach as well as an immediate  local impact.

Microglial Cell

One out of about every 10,000 girls is born with a mutation that causes autism-like behavior, stunts growth, and impairs the ability to think, sleep, and even breathe. There is no cure for the condition, known as Rett syndrome, but a new study of mice proposes that bone marrow transplants that increase a certain type of immune cell in the brain can lessen some symptoms. Researchers say the findings may be an important clue to the mechanisms of the disease, but they caution that much more work is needed to identify the treatment potential.

Rett syndrome results from mutations in a gene on the X chromosome called MECP2, which regulates the activity of other genes. Researchers replaced the mice’s immune systems by first exposing four-week-old mice to radiation to kill off their existing immune cells — including microglia — and then injecting them with bone-marrow cells with a working copy of MECP2. Stem cells in bone marrow form the immune system, including microglia cells.

Male Rett mice, with no working copy of MECP2, usually die within two months, but the ones that got bone marrow from healthy mice lived up to a year, Jonathan Kipnis, a neuroscientist at the University of Virginia School of Medicine in Charlottesville, who led the study says. The treated mice breathed easier, walked better and gained more weight compared with untreated mice. Female mice with just one working copy of MECP2 develop Rett symptoms later than male mice, but a bone-marrow transplant improved gait, breathing and weight gain for them, too.

The oldest of the treated mice has now lived almost a year, neuroimmunologists Noël Derecki who also worked on the study says. “This seems to stop the disease in its tracks.”

“If we show the immune system is playing a very important role in Rett patients and we could replace it in a safe way, we may develop some feasible therapies in the future,” says Kipnis.

Kipnis hypothesizes that microglia from Rett mice have trouble clearing cellular rubbish in the brain, making it more difficult for their neurons to work properly. Fixing MECP2 mutations with gene therapy is well beyond current technology, Kipnis notes. “But if we can improve the environment by adding microglia, which is feasible, we may be able to attenuate some aspects of the disease.” He’s not advocating clinical trials anytime soon, though. Although bone marrow transplants are already performed on children with leukemia and other cancers, the procedure carries a high risk of serious, and even fatal, side effects.

Less drastically, Kipnis thinks that the disease could also be treated with drugs that improve microglia function. Girls with Rett syndrome have one working copy of MECP2, so half of their microglia may work.

Frauke Zipp, a neuro-immunologist at the Johannes Gutenberg University Mainz in Germany, agrees that a clinical trial of cell transplantation to treat Rett syndrome is far afield, but not inconceivable if additional research pins down their role in disease.

“These findings contribute to the idea that Rett syndrome is a very complicated disorder involving multiple cell types and systems,” adds Gail Mandel, a neuroscientist at Oregon Health Sciences University near Portland. Some form of gene therapy may be a way of fixing all these different problems, she says.