RARE Daily

RNA-Targeted Therapy Shows Promise for a Rare Childhood Dementia

April 19, 2024

Rare Daily Staff

A study in mice suggests a new RNA-targeted therapy can halt the progression of a specific type of childhood dementia and holds potential to reverse some of the detrimental effects of this rare disease, researchers said.

Scientists from the University of Sydney’s Charles Perkins Centre and the School of Life and Environmental Sciences showed that the rare neurodegenerative condition Aicardi-Goutières Syndrome (AGS), which is driven by overproduction of interferon, can be effectively treated with an RNA-targeted therapy delivered into the central nervous system. In a study, published in The Journal of Clinical Investigation, researchers reported the treatment reduced neuroinflammation and neuronal damage and restored the integrity of the blood-brain barrier.

Aicardi-Goutières Syndrome (AGS) is among the more than 100 rare neurodegenerative genetic disorders identified as causing childhood dementia. Excessive production of interferon in the brain, part of the body’s defense against infection, leads to neuroinflammation and neurodegeneration. Although many newborns with AGS show no symptoms, they typically develop severe neurological issues and lifelong physical impairments within the first two years of life.

There is currently no cure available. Existing treatments for AGS focus on symptom management. The urgent need for an effective therapeutic approach has prompted researchers to explore innovative solutions.

The new approach targets the interferon alpha receptor using antisense oligonucleotides. These therapies are designed to seek out, bind to, and degrade messenger RNA (mRNA) in a highly specific manner, reducing the amount of disease-causing protein.

“Our understanding of the pathological processes involved in AGS has evolved significantly,” said Associate Professor Markus Hofer, who has investigated the molecular mechanism of AGS for ten years. “This research marks a crucial step forward in the quest for effective treatments for this devastating condition.”

This study was conducted in partnership with Ionis Pharmaceuticals, who developed the treatment, and Biogen, with further research underway. With animal studies now complete, the findings look set to inform human trials in the future.

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