A meeting of minds

Autism spectrum disorders will be better understood thanks to a substantial investment from a US-based philanthropic foundation to the University of Edinburgh.

One of the benefits of spending time at a world-leading university is the opportunity to rub shoulders with others who are similarly attracted to curious thinking, bold ideas and pioneering discovery.

Indeed, it is staggering to appreciate how significant such interactions can be: a conversation in the corridors of a researchinstitute, a coffee shared between seminars. These are the moments in which new partnerships can be forged and lasting progress begun.

It was just such an interaction that led to one of the largest philanthropic donations ever made to the University, given in aid of boosting scientific research into brain development and autism.

In April, the US-based Simons Foundation pledged £20 million to launch the Simons Initiative for the Developing Brain (SIDB). The funding will support pioneering studies into the biology that underpins changes to brain development, and could eventually lead to new ways to help people with autism.

The crucial conversation – or more accurately, the first of a number – came in June 2016, and involved Professor Jim Simons, a renowned mathematician, his wife Marilyn Simons, and Professor Peter Kind, Director of the University’s Patrick Wild Centre for Research into Autism, Fragile X Syndrome and Intellectual Disabilities.

Professor Simons was in Edinburgh to receive an honorary degree for services to his field and philanthropy. In 1984, Professor Simons set up the Simons Foundation with Marilyn. Their aim was to advance the frontiers of mathematics research and discovery science. Marilyn Simons now serves as President of the Simons Foundation Autism Research Initiative (SFARI) and the charity has become one of the leading philanthropic funders of autism research in the US. It was this special interest that led the pair to meet Professor Peter Kind.

It was a stimulating discussion. Being well-versed in the current landscape of global autism research, the Simons were keen to understand the approach taken by scientists at the Patrick Wild Centre, whose neuroscience research ranges from developing new animal models of neurological disorders to trialling new therapies.

A meeting of minds took place and, before long, the team were building a vision for a new avenue of research.

“In less than one year from that initial conversation, we established this initiative, which has the potential to transform our understanding of the autisms,” explains Professor Kind.

This is an amazing opportunity to bring together a range of scientific and clinical expertise at the university with the aim of understanding how the brain develops on multiple levels, including genetics, molecular biology, neural circuitry, behaviour and cognition.
Professor Peter Kind
Professor of Developmental Neuroscience

“This is an amazing opportunity to bring together a range of scientific and clinical expertise at the University with the aim of understanding how the brain develops on multiple levels, including genetics, molecular biology, neural circuitry, behaviour and cognition.

“By combining these approaches, we will learn how brains mature and gain valuable insights into the developmental origins of autism.”

Autism spectrum disorders will be better understood thanks to a substantial investment from a US-based philanthropic foundation to the University of Edinburgh.

The aim of the SIDB is to understand the science that will advance new diagnostic tools and better therapies to address the causes and consequences of autism. The conditions, which affect around 75 million people worldwide, affect social interaction and communication and are also defined by the presence of restricted or repetitive behaviours. The initiative will focus particularly on conditions at the severe end of the autism spectrum, where affected individuals also have marked intellectual disability and impaired motor control. In these cases, there is often a clearly identifiable genetic cause, which can be modelled in the laboratory.

The first step on that journey will be to develop new models of these diseases in mice, rats and human stem cells. Research using animals has been hugely significant in autism spectrum disorders and allows scientists to understand the biology of brain conditions in ways that simply would not be possible with other methods.

We will learn how brains mature, and gain valuable insights into the developmental origins of autism.
Professor Peter Kind
Professor of Developmental Neuroscience

“Unlike mice, rats are very social animals,” explains Professor Kind. “They hunt together and work in teams and therefore have extensive communication and interactions. For that reason, we can learn a great deal about how differences in brain biology and function can influence social behaviours.

“To date, many researchers have examined these conditions in adult animals,” he continues. “But we are particularly interested to understand if there is a window or windows of opportunity early on in brain development, where developmental differences can be reversed more effectively than if we intervened later. By comparing young and adult animal models, we hope to identify critical periods in development during which therapies may be at their most effective.”

Another Edinburgh scientist who shares this vision for reversing neurological disorders is Professor Sir Adrian Bird, who serves as deputy director of the SIDB.

Professor Bird became internationally celebrated in 2007, when he led groundbreaking efforts to reverse a genetic form of autism, called Rett Syndrome. The rare disorder, which causes physical and intellectual disability in young girls, is caused by a mutation in the gene known as MECP2.

By developing an animal model of the condition, his team found that when the key gene was restored, affected mice fully recovered even in adult animals. For the first time, he showed that the condition was, in mice, completely reversible. A key focus of the SIDB programme will be to investigate if this is the case for other neurodevelopmental disorders. Hopes are high that similar progress can be made by developing new models of other autism spectrum disorders.

“One of the key goals of this new initiative is to bring academics together from a variety of disciplines, and ask them to consider autism as their collective target,” says Professor Bird.

“Sometimes, scientists tend to hone in on one particular challenge– one molecular pathway or one particular gene. We are asking scientists to look at autism and consider everyone else’s challengeas their own. By uniting in that way, and gathering the broadest possible expertise, we have a far greater opportunity to make progress.”

Professor Kind and his team have not lost any time in making a start. With the Simons funding in place, the SIDB has already begun to lay out its scientific programme.

A principal focus will be to use advanced techniques to probe how the brain develops in the presence of DNA changes that are known to cause autism. Experts will investigate how variations in the wiring of the brain alter the way we process information – which ultimately underlies our intellectual and social abilities.

We will work together not only to share expertise, but to co-invest in new equipment and personnel to support both initiatives in the areas of animal behaviour, imaging, functional genomics and bioinformatics.
Professor Sir Adrian Bird
Buchanan Professor of Genetics

In addition to boosting our fundamental understanding of brain biology, the initiative will also enable scientists to work more closely with clinical teams that care for children and their families. One key element of the initial programme will be to build cohorts of people with genetic causes of autism, so that new therapies can be trialled as soon as they come on line.

The goals are ambitious, meaningful and ground-breaking, and hope ultimately to change the experience of living with conditions on the autism spectrum.

But the position of the SIDB within the Edinburgh Neuroscience community offers a further advantage.

“The culture here in Edinburgh is exceptionally collaborative,” explains Professor Bird. “None of us can be on top of the full gamut of the conditions we work on, and so we build strength by gathering people with different perspectives around one common goal.”

A crucial collaboration for the SIDB team will be with the newly-established Dementia Research Institute – a UK-wide initiative being led by University College London, which has its discovery science base in Edinburgh.

The £250 million institute, established by the Medical Research Council and dementia charities, aims to accelerate research into neurodegenerative diseases that lead to dementia.

At its heart is a drive to recruit young scientists who will identify strategies to help prevent dementia before symptoms appear and investigate new ways of improving care for people living with the condition.

“The UK DRI at the University of Edinburgh is tasked with illuminating mechanisms of dementias in a similar way to SIDB’s remit with respect to autism research,” says Professor Bird. “The two initiatives have natural links since several research groups are involved in both, and the techniques and approaches to uncover deficits at the synapse, cell, circuit and whole-animal level that underlie different brain disorders are surprisingly similar.

The culture here in Edinburgh is exceptionally collaborative. None of us can be on top of the full gamut of the conditions we work on, and so we build strength by gathering people with different perspectives around one common goal.
Professor Sir Adrian Bird
Buchanan Professor of Genetics

“The DRI and SIDB will work together not only to share expertise, but to co-invest in new equipment and personnel to support both initiatives in the areas of animal behaviour, imaging, functional genomics and bioinformatics.”

The neuroscience community in Edinburgh is surely thriving, and this shared energy, vision and optimism must count among the reasons why. For those living with, caring for or fearing some of the most challenging conditions we face, the future is looking hopeful.

“Professor Kind and his colleagues have been doing outstanding, innovative work, both in the lab and in their clinical studies,” says Marilyn Simons, President of the Simons Foundation. “We are proud to support this further exploration into the biology of the developing brain and feel confident that it will accelerate understanding of autism and hasten the development of meaningful treatments.”

Patrick Wild Centre

This article was published on 2023-11-10