Existing Drug Repurposed for Rare Autism via Genetic Fingerprinting

Developing new treatments for rare genetic disorders is notoriously slow and costly. To tackle this, researchers utilised a high-throughput drug discovery platform focused on 19q12 autism spectrum disorder (ASD), a rare condition linked to deficiencies in the ZNF536 and TSHZ3 proteins. Instead of testing on the patient directly, they first identified the condition's 'transcriptomic fingerprint'—the specific pattern of gene activity—within a laboratory disease model.

The team then screened various small molecule drugs on healthy (wild-type) cells to see how they altered genetic activity. They sought a specific match: a drug that induced the exact opposite effect to the disease's fingerprint. This search identified entrectinib, an already approved medication, as a prime candidate capable of normalising the dysregulated pathways associated with the disorder.

Moving from the lab to the clinic, entrectinib was prescribed off-label to a patient with 19q12 ASD. Subsequent blood analysis confirmed that the drug successfully recapitulated the desired effects, effectively normalising the disease signature in the patient's biomarkers. This study demonstrates a powerful shift in drug discovery. By using transferable genetic signatures, scientists can screen drugs in standard cell lines rather than relying solely on expensive, disease-specific models. This method offers a potentially universal, cost-effective route to repurposing drugs for rare conditions.