{"id":2444,"date":"2023-07-31T10:49:59","date_gmt":"2023-07-31T10:49:59","guid":{"rendered":"https:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=2444"},"modified":"2023-07-31T10:49:59","modified_gmt":"2023-07-31T10:49:59","slug":"autism-cures-may-be-closer-as-focus-turns-to-early-treatment","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/2444\/autism-cures-may-be-closer-as-focus-turns-to-early-treatment\/","title":{"rendered":"Autism cures may be closer as focus turns to early treatment"},"content":{"rendered":"

Fresh insights into the genes that cause the neurological disorder could open new routes for the prevention and perhaps even reversal of symptoms.<\/p>\n

By<\/em><\/strong>\u00a0\u00a0VITTORIA D\u2019ALESSIO<\/p>\n

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition that has been intensely investigated since the mid-20th<\/sup>\u00a0century. It\u2019s estimated that ASD affects around\u00a01 in 100<\/a>\u00a0children and mainly boys.<\/p>\n

Studies suggest that ASD is closely linked to genetics. The basic challenge is untangling the relationships between the many genes involved and the symptoms.<\/p>\n

Genes and symptoms<\/strong><\/p>\n

A focus on these links has the potential to enhance understanding of the condition and treatments for it.<\/p>\n

For instance, children born with a rare genetic mutation \u2013 on a gene called BCKDK \u2013 are more likely to develop impairments that, left untreated, would likely result in lifelong autism. Symptoms can include intellectual disability, epilepsy and a condition \u2013 microcephaly \u2013 where a baby\u2019s head is smaller than expected.<\/p>\n

The faulty gene in question disrupts the way the brain can process essential nutrients known as \u201cbranched-chain amino acids\u201d and creates the conditions for delayed neurological development.<\/p>\n

\u2018This got us thinking: now we know what causes this neurodevelopmental disorder, can we reverse it once the brain has developed?\u2019 said Gaia Novarino, a neuroscience professor whose team discovered the BCKDK mutation and its link to autism in 2012. \u2018Can we go back in time?\u2019<\/p>\n

Award winner<\/strong><\/p>\n

Novarino is a high-profile neuroscientist from Italy who has received numerous awards for her work in the field of autism research, including the Order of Merit of the Italian Republic.<\/p>\n

\u2018I have always been interested in genetic disorders and was struck by the general lack of understanding of paediatric, neurodevelopmental disorders,\u2019 she said. \u2018We know too little about these diseases.\u2019<\/p>\n

Because autism shapes the developing brain long before birth, many assume it\u2019s irreversible \u2013 a lifelong condition that, at best, can be managed with psychological support paired with speech and physical therapy.<\/p>\n

Some people prefer to forgo treatment because they don\u2019t believe autism needs to be cured, regarding it as an integral part of personality.<\/p>\n

\u2018Not everyone wants their ASD, or their child\u2019s ASD, to be treated,\u2019 said Novarino. \u2018If symptoms aren\u2019t profound, a person can live with the condition with minimal support and they may come to see their autism as an essential part of who they are.\u2019<\/p>\n

In any case, more recent research has led scientists to assess whether some forms of ASD may be treatable \u2013 either fully or in part.<\/p>\n

Mice tests<\/strong><\/p>\n

Novarino\u2019s team, based at the Institute of Science and Technology in Austria near Vienna, turned to mice for answers under a five-year European research project called\u00a0REVERSEAUTISM<\/a>\u00a0that ended in September 2022.<\/p>\n

Backed by EU funding, the researchers genetically engineered mice to be unable to process essential amino acids correctly, similarly to children with the BCKDK genetic mutation.<\/p>\n

Amino acids are protein building blocks needed for vital reactions within and between nerve cells. The body can\u2019t make amino acids itself and instead must find them from foods such as meat, fish, grains and nuts.<\/p>\n

The team found that rodents with the mutation developed both motor and social difficulties after birth.<\/p>\n

\u2018These mice have behavioural issues,\u2019 said Novarino. \u2018They also move in a strange way, with coordination problems.\u2019<\/p>\n

REVERSEAUTISM then took this research one step further to see whether, by injecting the missing amino acids directly into the brains of affected mice, their autism-like symptoms could be reversed.<\/p>\n

\u2018The answer was yes,\u2019 said Novarino. \u2018Not all symptoms disappeared, but there was considerable improvement in both social behaviour and coordination in mice that received injections. In other words, some signs of the disorder were reversed.\u2019<\/p>\n

Study of 21 infants<\/strong><\/p>\n

REVERSEAUTISM\u2019s findings so intrigued Dr Angeles Garc\u00eda-Cazorla of Spain that she decided to study whether children with a BCKDK deficiency showed symptom improvements after taking the missing amino acids as a food supplement in conjunction with a high-protein diet.<\/p>\n

Garc\u00eda-Cazorla is head of Metabolic Diseases Unit at the Hospital Sant Joan de D\u00e9u in Barcelona. The missing amino acids are leucine, valine and isoleucine.<\/p>\n

The study was based on 21 patients, aged between eight months and 16 months, recruited from centres around the world. The results were very promising.<\/p>\n

\u2018In general, all patients improved, in particular regarding the growth of their head, which means there was a proliferation of neurons,\u2019 said Garc\u00eda-Cazorla. \u2018They also showed improved motor function. Infants who weren\u2019t able to walk could now walk and infants who couldn\u2019t speak developed some basic language.\u2019<\/p>\n

Sooner the better<\/strong><\/p>\n

The earlier treatment was begun, the better the outcomes were.<\/p>\n

\u2018In the three children who started supplementation before the age of two, the evolution was much better and the child who started at eight months did best \u2013 she had normal brain development, with no signs of autism, by the age of three,\u2019 said Garc\u00eda-Cazorla.<\/p>\n

The study was carried out under an EU-initiated health alliance called the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN<\/a>), which is led by patients and experts.<\/p>\n

If future studies involving a larger cohort of BCKDK-deficient infants validate the results of the MetabERN investigation, Garc\u00eda-Cazorla and Novarino hope national health policies will be changed to require all babies to be tested for BCKDK deficiency at birth.<\/p>\n

This would form part of the newborn \u201cheel prick\u201d test, which checks up to 25 rare but serious health conditions.<\/p>\n

\u2018One of the challenges in the field of autism is that diagnosis is usually done quite late \u2013 rarely before the age of three or four \u2013 and at that point it becomes hard to treat,\u2019 said Novarino. \u2018Our work shows that starting supplementation early can make a real difference to people\u2019s lives.\u2019<\/p>\n

She and her team are pursuing this line of research in a European project called\u00a0SecretAutism<\/a>\u00a0that began in December 2022 and will run through November 2027. They received EU funding to grow brain tissue in the laboratory using human stem cells.<\/p>\n

By studying these \u201corganoids\u201d, the researchers hope to gain further insights into what exactly the many different genes associated with autism are doing in the body, the stages at which problems develop and how to interrupt the process.<\/p>\n

\u2018We\u2019re approaching this from many angles, trying to understand how else we can treat patients with ASD,\u2019 said Novarino. \u2018It\u2019s very complex research, but that won\u2019t put us off.\u2019<\/p>\n

Research in this article was funded by the EU via the European Research Council (ERC). <\/em><\/p>\n

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