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Synopsis B·Debate - Reconnecting the growing brain: from symptoms to mechanisms

On 26 and 27 November 2015, some of the best international experts in neuropaediatric diseases met during B·Debate to discuss the latest developments and challenges. With this Synopsis you will learn the main conclusions of the discussion.

10.02.2016

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Children’s brains are always growing and developing, but unfortunately this complex machine can also break down. Traditionally, pediatric neurology has addressed these problems according to the symptoms that cause them: epilepsy, mental retardation, autism and movement disorders, for example. However this approach isn't enough because the categories overlap and the symptoms are only the external manifestation of the underlying problem. Studying only these manifestations isn't normally enough to treat the problem.

In the words of Àngels García Cazorla, pediatric neurologist at Hospital Sant Joan de Déu Barcelona, we need “a little revolution in the way we approach, research and treat these disorders. The symptoms are important, but treatment must address the underlying mechanisms, not their consequences. And this is why we need to know what’s really going on inside the brain.”

In order to address and comment on all of these challenges and problems, to discuss the latest advances, some of the top experts in the world met for a session of B·Debate, an initiative of Biocat and the “la Caixa” Foundation to promote scientific debate.


Read the following synopsis and find out what was talked about at this debate. You can read the different sections of the synopsis following this text and the different themes located in the right column.
Main conclusions of the debate:
  • Neuropediatric diseases affect up to 20% of all children, but they have traditionally been researched less than those that affect adults.
  • Research has been addressed improperly, focusing on symptoms, which in many cases overlap between diseases, and not the mechanisms. This has made it difficult to find treatments that are truly effective.
  • We must study brain function from a microscopic and macroscopic point of view. From the synapses that connect neurons to the wiring that connects regions of the brain, what is known as connectome.
  • Treatments being studied include drugs to lessen certain disabilities, like Down syndrome; gene therapy and even light-activated drugs. 

 

1. Limitations of neurology in children

For Dr. García Cazorla, scientific leader of this B·Debate, "brain disorders in development are a very significant health problems that can affect up to 20% of all children, but historically they have been studied less than those in adults.” Xavier Castellanos, childhood psychiatrist and professor at the New York University School of Medicine, believes this could be because “children don’t vote and aren't in power, this could be why less money is invested in this type of research.”

"Brain disorders in development are a very significant health problems that can affect up to 20% of all children, but historically they have been studied less than those in adults.”  Dr. García Cazorla, pediatric neurologist at Hospital Sant Joan de Déu Barcelona

The errors that occur in the brain during childhood lead to a wide range of possible symptoms: epilepsy, disorders on the autism spectrum, movement disorders, mental disabilities, and more. García Cazorla says, “We’ve specialized in these, but basic neuroscience is growing, and that indicates that we are a bit disoriented, because the symptoms don’t reflect the exact decision of functioning: a mutation may manifest as epilepsy in some cases but as a movement disorder in others.” Or, as Castellanos puts it, “There are mutations that cause holoprosencephaly (serious malformation of the skull and face) in some children but only cause others to be missing a tooth. There are many factors involved.”

This lack of knowledge regarding the real mechanisms behind the symptoms makes if extremely difficult to come up with truly curative treatments because the therapies address the consequences but not the cause. This is why García Cazorla advocates for "a little revolution in the way we approach, research and treat these disorders. The symptoms are important, but treatment must address the underlying mechanisms, not their consequences. And this is why we need to know what’s really going on inside the brain.” A revolution that is not free from difficulties, as it must necessarily be transversal, involving people from many different disciplines. “There is the chance that we will disconnect instead of connecting, but that’s a risk worth taking,” she says.

In order to truly understand what is happening, it is necessary to study how the brain communicates. One on hand, on the microscopic scale, in terms of synapses that connect neurons. And, on the other, on the macroscopic scale, to untangle the structure of the wiring and how it works. And, at the same time, to look towards possible solutions. 


> Read more: 2. Micro and macro, from synapsis to circuits

There are many types of synapses in which various neurotransmitters participate and can be considered the keys to various locks in the brain.


 

“I’m very happy to come to the land of Ramon y Cajal and speak about the brain and its connectivity,” explained Sakkubai Naidu, podiatrist and neurologist at the Kennedy Krieger Institute in Baltimore, United States. “He said that neurons are contiguous, not continuous, and that they are dynamic.”

Read more

Biomedical research is complex in itself, but studying what are known as synaptic diseases adds additional difficulties. On one hand, because many of the genes involved have pleiotropic effects, meaning that altering them can lead to different effects. 

> Read more