New Insights to Understanding and Managing Intellectual Disorder

Insights for a potentially new therapeutic strategy to reduce associated cognitive impairment in an intellectual disorder (ATR-X) syndrome has been found, according to a recent study.

A new mechanism and a potential therapeutic strategy to decrease associated cognitive impairment in an intellectual disorder (ATR-X) syndrome has been investigated by researchers at Tohoku University in Japan, finds a study.

Researchers at Tohoku University in Japan have investigated an intellectual disorder (ATR-X) syndrome to reveal its cause, mechanism and a potential therapeutic strategy to decrease associated cognitive impairment.

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‘A potentially new therapeutic strategy has been found that could reduce associated cognitive impairment in an intellectual disorder.’

"Disease related neurodevelopmental disorders are rare and there is still a lack of therapy to treat the various syndromes," said Professor Kohji Fukunaga at the Graduate School of Pharmaceutical Studies, who led the study.

Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is a severe intellectual disability caused by ATRX gene mutations. The researchers found that treatment with 5-aminolevulinic acid (5-ALA), which is converted into G-quadruplex-binding metabolites, rescues decreased synaptic plasticity and cognitive deficits seen in ATR-X model mice.

The findings suggest a potential therapeutic strategy to target G-quadruplexes and decrease cognitive impairment associated with ATR-X syndrome.

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Among candidate ligands, 5-ALA has been applied clinically with minimal risk and approved for use following intracranial tumor resection in Europe, Canada, and Japan, where it has been used as a photosensitizer in photodynamic diagnostics applied in neurosurgery.

These clinical applications potentially reduce the required approval time and cost of clinical trials, as pre-existing absorption, distribution, metabolism, excretion (ADME) and toxicity data are readily available.

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The risk of failure is reduced as data relevant to 5-ALA safety and pharmacology is also available. The G-quadruplexes are involved in the pathology of other diseases and this discovery is expected to contribute to the possibility of new drug targets.

"5-aminolevulic acid is proven to be safe and is already used in supplements in Japan, so we are ready to begin clinical trials," says Fukunaga. "There is also evidence that it may improve autism spectrum disorders which is a common disease in Japanese children."

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Source-Eurekalert