Recent discoveries in epigenetics could soon make a clinical difference for children with attention-deficit/hyperactivity disorder, autism spectrum disorder, and other conditions, according to an expert.

The implications go beyond targeting treatment for an individual child in your practice based on a specific genetic mutation, Dr. Hakon Hakonarson, director of the center for applied genomics at the Children’s Hospital of Philadelphia, said at a pediatric update sponsored by Miami Children’s Hospital. Recent advances point to gene alterations that modify shared pathways, so the potential for wider application beyond ADHD and ASD — such as unexpected discoveries related to pediatric neuroblastoma — is a real possibility.

Dr. Hakonarson is a member of ICare4Autism’s Advisory Council and will be speaking about the gene networks underlying autism targeted for therapeutic intervention at the upcoming ICare4Autism International Autism Conference being held in Israel.

Hakon Hakonarson, M.D., Ph.D., is an associate professor of Pediatrics at The University of Pennsylvania School of Medicine.  He is a physician-scientist and director of The Children’s Hospital of Philadelphia’s Center for Applied Genomics (CAG), a high-throughput highly automated genotyping facility founded to identify the genetic causes of complex medical disorders in children, such as autism and cancer, with the objective of developing new therapies.

Dr. Hakonarson has an extensive track record in human genetics and has developed an international reputation amongst his peers. He has served previously in several senior posts in the biopharmaceutical industry, including as the director of Inflammatory and Pharmacogenomics Research and the vice president of Clinical Sciences and Development and CSO.

Dr. Hakonarson has also been the principal and co-principal investigator on several NIH-sponsored grants, and he has published numerous high-impact papers on genomic discoveries and their translations in some of the most prestigious scientific medical journals, including Nature, Nature Genetics and The New England Journal of Medicine.

Time Magazine listed Dr. Hakonarson’s autism gene discovery reported in Nature, 2009, among the top 10 medical breakthroughs of that year. With over ten years of experience in pioneering genomics research and genome-wide mapping and association studies, Dr. Hakonarson has intimate knowledge of the complexities of large-scale genomics projects and has put together the necessary infrastructure and workflow processes to unravel these complexities.

The Parent Child Training Program (PCTP) at Action For Autism is a ‘model’ program that addresses the critical need for parent education. How to parent an autistic child is not an intuitive process. True parental involvement is the key to successful autism programming and activities.

PCTP’s training empowers parents to take charge of their children’s health and education. Parental involvement on this level not only helps educate children, but it heals the emotional stresses that parents face. The PCTP training program is a ten-week country wide opportunity.

The coursework covers behavior modification and skills maintenance. Mothers learn tools and tactics for facilitating learning. Most importantly, they gain confidence through community by meeting other parents. This is the goal of ICare4Autism’s conference and our institute at large. By sharing information we strengthen our skills.

Ms. Barua’s organization quotes that they hope for “a society that views the interdependence of people of every ability as valuable and enriching.” AFA seeks to provide equal opportunities for all. Their goals are not only research and expanding autism education in India but also independent life training and skills.

The AFA’s reach goes beyond Los Angeles and India to the Europe. AFA created “Activate Yourself!” to put into action the value of all people. Due to the nature Autism, people with this disorder have difficulties in terms of self-advocating their fundamental rights. Therefore “Activate Yourself” was developed to encourage active participation of young people with ASD; empower them as active citizens, make them aware of their role in creating their own future and promote their equal rights and opportunities. The project is supported by the Youth in Action Programme of the European Union.

This kind of active work is right in line with the International Center for Global Research. We learn as much in the classroom as we do from the scientists in our lab. How to educate our autistic youth comes directly from their communication and achievements.

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.

The daily encounters and friction between the staff of therapists and the families of children with special needs (and sometimes also with the extended family) are often obscured within the obligations of rather complicated professional and mental challenges.

The family of the special needs child – who face a tremendous financial burden on top of the emotional burden they already bear – loses its privacy; they find themselves exposed, against their will, to the team of therapists. Often there are sensitive situations which cannot be hidden, and sometimes the family encounters open or latent criticism. The therapists also find themselves privy to the difficult emotional situation of the family members; crises in the relationships between the child’s parents; and complicated ethical problems: all of which while they are supposed to be providing professional and appropriate treatment for the child with whom they are working.

Inbar Konforti will be speaking about bridging the gap between families and therapists in home-based ABA at the upcoming ICare4Autism International Autism Conference in Israel.

The presentation will cover how parents and family members should be supported and involved in the treatment process, the difficulties experienced by the parents of children with special needs during such complex treatment and the difficulties experienced by the therapists.  She will also discuss how to optimize the effectiveness in applying such a home involvement program.

Inbar Konforti is the founder and Director of the Refael Center (www.merkaz-refael.co.il) – the National Guidance Center to Train Behavioral Therapists ABA; Certified Behavior Analyst BCABA, with 12 years’ experience working with children suffering from autism and delayed development. She is a graduate of the University of Tel Aviv for certification studies in Applied Behavioral Analysis. BA (Honors) in Special Education from Bar Ilan University. Inbar Konforti is a lecturer on ABA at various locations in Israel, instructor of the Home-Based Program, and programs designed to integrate children suffering from autism and delayed development into schools and kindergartens.

Dr. Eli Hatchwell is a member of ICare4Autism’s Advisory Council and will be speaking at ICare4Autism’s International Autism Conference in Jerusalem this August.  He will be speaking about the heritability of autism and will discuss the recently completed project he was involved with which discovered many novel genes in connection with autism.

Dr. Hatchwell’s clinical and technical expertise in investigating human genetic disorders led him to recognize early on that human genetic diversity was grossly underestimated, there was a critical need to comprehensively understand the vast spectrum of normal genetic variation in the population and that rare variants are largely responsible for causing common disease – the underlying principles of the genetic biomarker discovery technology of Population Diagnostics.

He is recognized as a key collaborator in the development of one of the first genome-wide BAC-based comparative genomic hybridization (CGH) microarray platforms and remains at the forefront of cytogenetic and genome analysis through early adoption of leading edge technologies. Dr. Hatchwell collaborates with human genetics researchers worldwide, is a coauthor on numerous peer-reviewed articles, encompassing both clinical genetics and genome technologies, and is senior editor of a book series aimed at educating medical specialists on genetic principles and practices.

Dr. Hatchwell is also a certified Medical Geneticist (UK) with many years of experience in clinical practice. He received his medical degree from the University of Cambridge, his DPhil in Molecular Genetics from the University of Oxford, and was a Wellcome Advanced Clinical Training Fellow. He also holds a degree in Mathematics from the Open University (UK).

His goal is to get together as many genes to formulate tests that are as comprehensive as possible so that autism could be diagnosed medically before clinically. He is also interested in matching genetic causes of autism to potential therapeutic interventions. He believes these complex genetic disorders, will eventually be found to be amalgams of very a variety of very rare disorders.

Furthermore, this kind of research could lead to better treatments for a subset of children with elevated levels of certain compounds in their urine, said James Woods, a researcher at the University of Washington who worked with Battelle researchers on the project.

While the study was relatively small, including 76 boys, Nick Heyer, a senior research scientist at Battelle’s Seattle lab, who worked on the study and said he’s hopeful it can be replicated on a larger scale and lead to a widely available screening test for babies.

“If it can detect increased risk of autism at age 1, that would be fantastic,” he said. “It’s the only biomarker (test) I’m aware of that could be done non-invasively and fairly inexpensively.

“I’m really pretty optimistic and excited about getting it retested.”

Heyer said he is trying to incorporate the urine test into a study that will include 1,200 mothers who have autistic children and are pregnant again. The researchers would follow the new babies’ development through age 3. He’s also working with a laboratory in South Korea to reproduce the study in a larger group.

The test looks for elevated levels of compounds called porphyrins and costs between $50 and $100. Woods said the cost would come down if the test were used frequently to screen babies.

Woods said everybody has the compounds in their urine, but some of the children in the study had clearly elevated levels.

The study included only boys, who are much more likely to have autism than girls, but the test likely would work for both genders based on other research, Woods said.

Heyer said there’s been speculation that elevated porphyrin levels are connected to mercury exposure in children with autism, but the research team found no link to increased exposure to mercury, leaving open the question of why the compounds are higher in some children with autism.

“I’m not a supporter of the concept that this is due to mercury exposure,” he said. “There’s no evidence in my mind that that should be the reason for this.”

Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, et al. 2010 Urinary Porphyrin Excretion in Neurotypical and Autistic Children. Environ Health Perspect 118(10): doi:10.1289/ehp.0901713

Overall, they found autism had been diagnosed in 10 percent to 11 percent of full siblings and 5 percent to 7 percent of half-siblings.

The new finding may not be a surprise – given that half-siblings share about 25 percent of their genes – but provides new clues to how autism is inherited.

The study included more than 5,000 U.S. families enrolled in a nationwide autism registry in which there was a child with autism and at least one other sibling. Included were 619 families with at least one maternal half-sibling, meaning the children shared the same mother but not the same father. The researchers compared autism recurrence among the half-siblings to the rate among the full siblings.

The researchers also looked at half-siblings in a group of St. Louis families to try to replicate the findings from the larger study.

“We found that autism risk for half-siblings is about half of what it is for full siblings,” principal investigator Dr. John Constantino, director of child and adolescent psychiatry at the Washington University School of Medicine in St. Louis and psychiatrist-in-chief at St. Louis Children’s Hospital, said in a university news release.

“Most of the half-siblings we studied had the same mothers. Given that half of the risk of transmission was lost and half was preserved among those maternal half-siblings, mothers and fathers appear to be transmitting risk equally in families in which autism recurs,” Constantino said.

The findings also suggest that in many families, the transmission of autism from parents to children is the result of the effects of many genes, with each contributing a small proportion of the risk, he said.

The study was published online April 16 in the journal Molecular Psychiatry.

Sources:

J N Constantino, A Todorov, C Hilton, P Law, Y Zhang, E Molloy, R Fitzgerald, D Geschwind. Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD. Molecular Psychiatry, 2012; DOI:10.1038/mp.2012.9

Washington University in St. Louis (2012, April 17). Study of half siblings provides genetic clues to autism. ScienceDaily. Retrieved April 23, 2012, from http://www.sciencedaily.com­/releases/2012/04/120417143849.htm

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.

We have known for many years that autism is more common in boys than girls. Latest CDC figures show that as much as 5 times as many boys are diagnosed with autism than girls. The disorder appears different in the sexes, and these differences may have important implications for both diagnosis and treatment.

There is currently no adequate explanation for this imbalance in the sex ratio, but Dr. Peter Szatmari, a professor and the head of the Division of Child and Adolescent Psychiatry in the Department of Psychiatry and Behavioral Neurosciences at McMaster University believes that something could be protecting girls from developing ASD and other developmental disorders. That factor could be hormone levels in utero, epigenetic factors that turn autism susceptibility genes “on” and “off” during development, or the fact that young girls have in general better social skills than boys and so need a bigger “dose” of what causes ASD to cross that threshold to being impaired.

Dr Szatmari explains “It is possible that those possible protective factors, once identified and understood, could play an important role in pointing toward new treatments and interventions that capitalize on those protective factors and so make a real difference to long-term outcomes.”

The clinical expression of autism is also different in boys. Generally speaking, girls with autism have greater learning disabilities and more problems academically than boys.

Higher-functioning girls with ASD are may be missed by clinicians who are not experts in diagnosis, Dr Szatmari states. There is some evidence that among this subgroup, girls have better social skills than higher-functioning boys with ASD and so are not diagnosed as readily. Although, the symptoms of ASD can appear as extreme shyness or anxiety in girls, masking that they may not be responsive to the social cues of others.

Girls on the autism spectrum have fewer repetitive behaviors such as rocking and spinning and less sensory sensitivity than boys with ASD. Since these signs are subtle, doctors may not recognize the disorder. Diagnosis at a later age reduces the chances of early treatment, which is understood to provide a better outcome.

Some evidence suggests that girls with ASD are bullied less often than boys. They appear to blend in more easily with their peers and are less often the victim of bullying by other girls.

Understanding these differences both biologically and experientially holds the promise of improving the long-term outcome of all children with ASD. Most important, clinicians need to be sensitive to how the disorder shows up in girls so that those affected can receive early intervention as soon as possible.

Dame Stephanie Shirley

Dame Stephanie Shirley is the British Government’s Founding Ambassador for Philanthropy, and the Chairman of the Shirley Foundation. The keynote speaker of the upcoming ICare4Autism International Autism Conference, Dame Shirley, recently expressed her thoughts on philanthropy and how to invigorate a giving culture.

Dame Shirley explained the result of having arrived in theUKin 1939 as an unaccompanied child refugee fromGermany, “my personal history is the main reason why I give. As a refugee, I need to justify the fact that my life was saved while so many others were lost. I’ve been the recipient of charity and have been sensitized to issues in a way that people who have always had enough money – not to be hungry anyway – find hard to imagine”.

She sites her two life-defining ideas as first, knowing that there is always hope and second, that even after losing everything she was never the victim of bigotry and cruelty.

Dame Shirley believes that it is important not to patronize beneficiaries and the key to this is for modern philanthropists to be actively involved.  She also believes the more open we are about our giving the more we will encourage a giving culture saying, “If I don’t talk about why and how I give, how can I get anyone else involved? A society needs models, strong models, to display personal vision and leadership.”

She also noted that there needs to be a shift in the way that governments, media and nonprofits interact with philanthropists.  Dame Shirley states that giving is voluntary and philanthropist don’t always respond to the most ‘needy’ so it is naïve for governments to rely on philanthropists to pick up the slack when services are cut.  She states that that the media need to find a way to both praise and critique the work of philanthropists.  Dame Shirley believes that nonprofits need to encourage their donors to voice their support to inspire others to follow in their footsteps.

The thoughts she wanted to leave the audience with were succinct and inspiring, “One: Be strategic in your giving. Make a difference. Two: Provide a role model. Be prepared to stand up and be counted. And: Always, but always, be humane.”

ICare4Autism International Autism Conference will be held in Jerusalem on the 1st and 2nd of August 2012. Autism: A Global Perspective will bring together top leading medical and educational professionals and researchers working in autism.

The purpose of the ICare4Autism conferences are to share current groundbreaking research into the causes and treatment of Autism Spectrum Disorders , and to be a catalyst for powerful interdisciplinary collaborations to tackle the global autism crisis. Registration is now open.