Around 1% of children are diagnosed with autism spectrum disorders (ASD), yet there are currently no drugs designed specifically to treat their main symptoms. Working to change this is the IMI-funded EU-AIMS project. The goal of EU-AIMS is to generate tools that will enhance our understanding of ASD, and ultimately pave the way for the development of new, safe and effective treatments for use in both children and adults. As well as dramatically improving quality of life, good treatments would help to cut the social and economic costs of ASD.
ASD refers to a diverse group of development disorders that are characterised by difficulties in social interaction and communication, and the presence of unusual repetitive behaviours. It affects one child in 110, with boys at greater risk of developing ASD than girls. ASD is a lifelong condition, and for reasons which are not fully understood, the prevalence of ASD is rising.
The precise symptoms and their severity vary widely from one person to another; some are only mildly afflicted and can lead relatively independent lives, while others are severely disabled and require a lot of specialist care. Furthermore, while some individuals are intellectually impaired, others excel in areas like maths and music. Finally, to add to the complication, many people with ASD suffer from other conditions, such as seizures. This diversity of symptoms means that diagnosing ASD is far from easy, and in fact it was only formally recognised as a condition relatively recently.
An urgent need for effective treatments
Today, there are no drugs designed specifically to treat ASD; instead, those affected are treated with medicines designed for other conditions. The good news is that recent research has shed new light on the neurobiology behind ASD and identified some genes that increase the risk of autism. The findings suggest that it may actually be possible to treat ASD, something that was once thought to be impossible.
EU-AIMS – aiming high
EU-AIMS represents the first time that major pharmaceutical companies are joining forces, along with experts from academia, regulatory authorities and patient groups, to accelerate the development of innovative drugs to treat this complex disorder. In terms of both budget and scope, it is the largest initiative of its kind in the world. EU-AIMS will generate new tools to study the biology behind ASD and test the efficacy of potential treatments. For example, the team will gather samples from people bearing certain mutations associated with ASD; this will pave the way for the generation of cell lines that can be used to test treatments.
Elsewhere, the researchers will advance the use of brain scans as a tool to boost ASD drug discovery and also identify which people with ASD might respond best to a given drug. The project will also create a pan-European network of clinical sites. As well as making it easier to run clinical trials, this network will create an interactive platform for those with ASD and professionals. Ultimately, the project aims to come up with methods and tools to develop effective treatments for ASD (in both children and adults) as well as tools to diagnose ASD and assess symptoms in the clinic.
Relief for patients
Despite the lack of effective, dedicated ASD treatments, almost three quarters of children with ASD are on medication developed to tackle symptoms like tics, seizures, and hyperactivity. However, there is little evidence to suggest that the benefits outweigh the unpleasant side-effects of these drugs. Furthermore, little is known about what treatments are effective in adults. By paving the way for the development of new treatments, EU-AIMS is set to dramatically improve the quality of life of the growing numbers of people with ASD. In addition, EU-AIMS will help to cut the heavy economic and social costs of autism.
Turning Europe into a hotspot for autism research
EU-AIMS brings together Europe’s top ASD researchers from academia, the pharmaceutical industry and patients’ organisations. The partners have expertise in disciplines such as cell biology, behaviour, drug discovery, patient advocacy, clinical trials, genetics, psychiatry, brain imaging, and more.
By linking up these experts and creating a pan-European network for both people with ASD and professionals, EU-AIMS will place Europe firmly on the ASD research map and give Europe’s pharmaceutical sector a competitive edge when it comes to getting novel ASD drugs to the market and the patient.
Achievements & News
EU-AIMS highlights gender differences in autism
Autism affects different parts of the brain in males and females, reveals new research from IMI project EU-AIMS published in the journal Brain. The findings suggest that ###researchers should stratify their results by gender and avoid assuming that results found in males also apply to females.
The team used magnetic resonance imaging (MRI) scans of both healthy adults and adults with high-functioning autism to determine whether the condition affects male and female brains in the same way or differently. They found that the brain areas that were atypical in women with autism are similar to the areas that usually differ between males and females, lending support to the idea that females with autism show neuroanatomical ‘masculinisation’. In the men with autism, different brain areas were affected.
‘This is one of the largest brain imaging studies of sex/gender differences yet conducted in autism. Females with autism have long been under-recognised and probably misunderstood,’ commented Dr Meng-Chuan Lai of the University of Cambridge, who led the research. ‘The findings suggest that we should not blindly assume that everything found in males with autism applies to females. This is an important example of the diversity within the ‘spectrum’.
EU-AIMS researcher scoops prestigious prize for women in science
Emily Jones, a Birkbeck College researcher working on IMI’s autism project EU-AIMS has won a prestigious L’Oréal-UNESCO UK & Ireland For Women In Science (FWIS) Fellowship. ###Dr Jones is particularly interested in the early development of basic skills in children with autism spectrum disorder (ASD), as this contributes to our understanding of the underlying causes of autism and could pinpoint targets for intervention. In EU-AIMS, Dr Jones coordinates a large cross-European study of infants at high familial risk for autism.
The FWIS award is worth GBP 15 000 (approx. EUR 17 500), and winners can spend it on whatever they need to further their career, including equipment, travel, and childcare costs. ‘The fellowship will allow me to buy crucial equipment that I require to investigate the link between attention and arousal in the development of autism,’ says Dr Jones. ‘Combining a research career with family responsibilities can be challenging, and the flexible support provided by the fellowship will help me achieve the right balance.’
Now in their seventh year, the FWIS awards were established with the goal of promoting the greater participation of women in science by offering awards to outstanding female postdoctoral researchers.
Babies at risk of autism show reduced response to social cues, EU-AIMS study reveals
Babies aged 4-6 months that are at risk of autism show a reduced response to social cues compared to other babies, according to new research from IMI’s EU-AIMS project published in the Proceedings of the Royal Society B. ###The symptoms of autism, which include difficulties in social interactions and communication, emerge gradually during early childhood, and firm diagnoses are only made in children aged two and up. Until now, little research has focused on what happens in children below that age. In this study, the team studied brain activity in babies that are known to be at risk of autism as they have an older brother or sister with autism (autism being a highly heritable condition) and infants with no family history of the condition. Wearing caps bearing sensors, the babies watched videos of human actions (such as the game of ‘peek-a-boo’) or listened to human sounds (laughter, yawning) and non-human sounds (e.g. running water). The results showed that the high-risk babies responded less to the social cues than the low-risk babies, and furthermore the brain activity patterns seen closely resemble those of children and adults with autism. The researchers point out that the next step would be to assess the children when they are older to see which youngsters, if any, actually develop autism symptoms. In a press release by Birkbeck College (which is not an EU-AIMS partner), a mother of one of the babies involved in the study said: ‘Having been through this myself, I felt it was my duty to ensure I helped in any way I could by involving [my son] in the Babylab research. I feel very strongly that this is a very important start towards improving the lives of many families with children on the autistic spectrum.’
IMI brain projects in the spotlight in New Orleans
Autism project EU-AIMS held an IMI networking event at the annual meeting of the Society for Neuroscience (SfN) in New Orleans, US, on 16 October. ###The SfN annual meeting is the world’s biggest gathering of neuroscientists, attracting 30 000 attendees from around the world. The networking event was therefore an excellent opportunity for EU-AIMS to promote its work to the neuroscience community.
IMI-funded scientist wins major neuropsychopharmacology award
Andreas Meyer-Lindenberg of the Central Institute of Mental Health in Mannheim, Germany and a participant in IMI’s NEWMEDS and EU-AIMS projects has been awarded the prestigious ECNP Neuropsychopharmacology Award 2012###for his groundbreaking work linking genetic variation associated with risk of mental illness to brain structure and function. The award, handed out at the annual congress of the ECNP (European College of Neuropsychopharmacology), recognises innovative and distinguished research achievements in neuropsychopharmacology and related fields. Dr Meyer-Lindenberg’s work focuses on the genetic and environmental risk factors associated with psychiatric diseases such as schizophrenia. ‘Especially our recent work on rare, high-risk genetic variants associated with schizophrenia and autism would not have been possible without the cooperative science funded in IMI,’ Dr Meyer-Lindenberg said.
Could autism brain changes be reversed?
Autism Spectrum Disorders (ASD) refers to a complex of different conditions. In some cases ###autism is present together with other conditions (e.g. epilepsy) as part of a syndrome caused by a single, specific gene mutation (e.g. Fragile X), but in the majority of patients its causes are largely unknown and could include different genetic and environmental factors. Certain brain changes in syndromes with autism appear to be reversible, and new research from the IMI-funded EU-AIMS project suggests that this may also be the case for the broader autism population. The study, published in Science, looked at the effects of the loss of the neuroligin-3 gene in mice. Neuroligin-3 is involved in the transmission of nerve signals and has been linked to heritable forms of autism. In this study, researchers found that mice lacking neuroligin-3 produced unusually high levels of a specific glutamate receptor. Glutamate receptors are proteins that are known to be involved in memory and learning; the high levels of glutamate receptor production in the mice in this study impaired the learning process, thereby disrupting brain development in the long term. However, the researchers did not stop there – they reactivatedneurligin-3 production in the mice and found that this effectively returned glutamate receptor production levels to normal. Furthermore, the structural, autism-like defects in the brains of the mice disappeared. The findings suggest that there may be common deficits in the brains of individuals affected by many different forms of autism, and that drugs designed to target these glutamate receptors could halt the development of autism or even reverse it. The work was widely covered in the press, including in the Wall Street Journal and on Swiss TV (in French).
IMI autism project EU-AIMS on the cover of Nature
IMI autism project EU-AIMS starred as Nature’s cover story with its research revealing that the father’s age when a child is conceived is ###the biggest single contributor to the number of new mutations passed on to a child. The findings suggest that the increase in the number of autism cases may be due in part to the fact that the average age of fathers at the time of conception is on the rise. The researchers arrived at their results after studying the genomes of around 2 000 Icelanders, including some with a diagnosis of autism or schizophrenia. On average, for every one-year increase in the father’s age, an additional two mutations were passed on to the offspring. ‘Our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases, and the chance that a child would carry a deleterious mutation that could lead to diseases such as autism and schizophrenia increases proportionally,’ said lead author Kari Stefansson of Iceland’s deCODE Genetics . ‘It is of interest here that conventional wisdom has been to blame developmental disorders of children on the age of mothers, whereas the only problems that come with advancing age of mothers is a risk of Down syndrome and other rare chromosomal abnormalities. It is the age of fathers that appears to be the real culprit.’
EU-AIMS adds to understanding of underlying causes of heritable autism
Elsewhere in the EU-AIMS project, researchers have shed new light on the workings of proteins called neuroligins that are involved in the transmission of nerve signals and have been linked to a heritable form of autism. ###Nerve signals are transmitted from one nerve cell to another at junctions called synapses. Neuroligins are found on the receiving side of synapses; if they malfunction or are absent, nerve signals are not transmitted correctly. The research, published in the Biochemical Journal , focuses on the functioning of neuroligins in mice. Mice have four kinds of neuroligin (dubbed neuroligins 1-4), and this study reveals that these neuroligins form pairs (‘dimers’) featuring either the same kind of neuroligin or different kinds of neuroligin. This is important because if neuroligin 3 pairs up with neuroligin 1, a mutation affecting neuroligin 3 will also indirectly impact neuroligin 1’s functioning. As neuroligin 3 is linked with heritable autism, many scientists use mice with mutated neuroligin genes as a mouse ‘model’ of autism in their work. These new findings will help to determine how well these mouse models work. Looking to the future, the team now plans to study the physiological and functional consequences of the loss of neuroligin 3. Elsewhere, the EU-AIMS team has had a paper published in Molecular Psychiatry setting out some of the latest findings in autism research and highlighting their potential importance.
- F. Hoffmann-la Roche AG, Basel, Switzerland
- Eli Lilly and Company Ltd, Basingstoke, UK
- Institut de Recherches Servier, Suresnes, France
- Janssen Pharmaceutica NV, Beerse, Belgium
- Pfizer Ltd, Sandwich, UK
- Vifor SA, Villars-sur-Glâne, Switzerland
Universities, research organisations, public bodies, non-profit groups
- King’s College London, London, UK
- Birkbeck College, London, UK
- Central Institute of Mental Health, Mannheim, Germany
- Commissariat a l’Energie Atomique et aux Energies Alternatives, Paris, France
- European Molecular Biology Laboratory, Heidelberg, Germany
- Institute of Education, London, UK
- Institut Pasteur, Paris, France
- Karolinska Institutet, Stockholm, Sweden
- Max-Planck-Gesellschaft zur Förderung der Wissenschaften eV, Munich, Germany
- Stichting Katholieke Universiteit / Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
- Universita Campus Bio Medico di Roma, Rome, Italy
- Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
- Universität Basel, Basel, Switzerland
- Universität Ulm, Ulm, Germany
- University of Cambridge, Cambridge, UK
- Autism Speaks, Princeton, US
- GABO: millarium, Munich, Germany
- Islensk Erfdagreining ehf, Reykjavik, Iceland
- NeuroSearch A/S, Ballerup, Denmark
Facts & Figures
|IMI funding||19 500 000|
|EFPIA in kind||7 900 000|
|EFPIA US||1 700 000|
|Other||6 800 000|
|Total cost||35 900 000|
F. Hoffmann-la Roche AG
Tel: +41 61 688 6350
Managing Entity for EU funds
King’s College London
Tel: +44 207 848 0984