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Precision Medicine Approach Reveals Targeted Therapy for Neurological Disorder
Nerve Cells.

A new study from Undiagnosed Diseases Network (UDN) researchers shows how careful study of a genetic condition can be critical for determining the best possible treatment. In a recent manuscript, UDN investigators from Baylor College of Medicine studied 5 individuals with similar neurological conditions characterized by a developmental delay and difficulty with mobility and speech. All five individuals had a mutation in the same gene, CACNA1A. CACNA1A encodes the information to make part of a protein called a calcium channel that is important for the function of neurons. Four of the five individuals had that exact same change, but one was unique. The unique mutation was seen in a ten-year-old girl named Avery who was enrolled as a participant in the UDN.

It was known that other mutations in CACNA1A lead to a spectrum of neurological disorders, so the researchers tested whether the new mutations caused a loss of function of the calcium channel. Given that Avery had more severe symptoms than the other four patients, it was possible her unique mutation resulted in a less functional calcium channel than the channel from the other four patients. To test this idea, the UDN researchers modeled each patient mutation within a model organism, the fruit fly. These mutations caused similar neurological defects in the fly compared to the symptoms seen in the patients. Surprisingly, the calcium channel with change analogous to Avery’s mutation was not less functional, it was more functional than the normal protein, allowing more calcium to enter nerve cells. This excess calcium can be toxic to nerve cells, which would lead to the defects. This finding had important implications for Avery’s treatment. Patients with CACNA1A mutations are often given medication to help compensate for the lack of function in the calcium channel, however Avery is now being treated with a drug to block the overactive calcium channel based on this research. This study highlights the power of a precision medicine based approach in which targeted therapies are designed for individuals based on precise molecular diagnoses. 

To learn more about Avery and this diagnosis, check out this story on or visit Avery's Participant Page on the UDN Coordinating Center website.


This page last reviewed on August 24, 2023