Could a 100 year old sleeping sickness treatment reverse autism?


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A century-old drug for treating sleeping sickness also temporarily reverses symptoms of autism in mice, researchers have claimed.

They say the drug restored normal cellular signaling in a mouse model of autism in animals that were the human biological age equivalent of 30 years old.

However, the team found the effects only lasted for around five weeks.

A transmission electron micrograph of cell mitochondrion. Researchers say their drug restored normal cellular signaling in a mouse model of autism, where signalling is damaged.

A transmission electron micrograph of cell mitochondrion. Researchers say their drug restored normal cellular signaling in a mouse model of autism, where signalling is damaged.

WHAT CAUSES AUTISM?

Naviaux said one of the universal symptoms of autism is metabolic disturbances.

'Cells have a halo of metabolites (small molecules involved in metabolism, the set of chemical processes that maintain life) and nucleotides surrounding them.

'These create a sort of chemical glow that broadcasts the state of health of the cell.'

Cells threatened or damaged by microbes, such as viruses or bacteria, or by physical forces or by chemicals, such as pollutants, react defensively, a part of the normal immune response, Naviaux said, and communications between cells are dramatically reduced.

If this  occurs during childhood, for example, neurodevelopment is delayed.

'Cells behave like countries at war,' said Naviaux.

'When a threat begins, they harden their borders. They don't trust their neighbors.'

'One way to look at this related to autism is this: When cells stop talking to each other, children stop talking.'

'Obviously correcting abnormalities in a mouse is a long way from a cure in humans, but we think this approach is a new and fresh way to think about and address the challenge of autism,' said Robert K. Naviaux at the University of California, San Diego School of Medicine.

The team tested the effect of suramin, a well-known inhibitor of purinergic signaling that was first synthesized in 1916 and is used to treat trypanosomiasis or African sleeping sickness, a parasitic disease.

 

'The discovery that a single dose of medicine can fundamentally reset metabolism for weeks means that newer and safer drugs might not need to be given chronically,' he said.

'Members of this new class of medicines might need to be given only intermittently during sensitive developmental windows to unblock metabolism and permit improved development in response to many kinds of behavioral and occupational therapies, and to natural play.'

Naviaux said the findings fit neatly with the idea that autism is caused by a multitude of interconnected factors: 'Twenty percent of the known factors associated with autism are genetic, but most are not.

'It's wrong to think of genes and the environment as separate and independent factors. Genes and environmental factors interact.

'The net result of this interaction is metabolism.'

The researchers found that suramin blocked the extracellular signaling pathway used by ATP and other mitokines in a mouse model of autism spectrum disorder (ASD), ending this cell danger response and related inflammation.

A single dose remained effective in the mice for about five weeks, and then washed out. It also cannot be taken long-term since it can result in anemia and adrenal gland dysfunction.

A single dose remained effective in the mice for about five weeks, and then washed out. It also cannot be taken long-term since it can result in anemia and adrenal gland dysfunction.

Cells subsequently began behaving normally and autism-like behaviors and metabolism in the mice were corrected.

However, the biological and behavioral benefits of suramin were not permanent, nor preventive.

A single dose remained effective in the mice for about five weeks, and then washed out.

It also cannot be taken long-term since it can result in anemia and adrenal gland dysfunction.

However, Naviaux said these and earlier findings are sufficiently encouraging to soon launch a small phase 1 clinical trial with children who have ASD later this year.




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