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New FAST-funded Study on Brain-Derived Neurotrophic Factor Activity

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Last November, we announced our new FAST-TRAC Grant recipient, Dr. John Marshall at Brown University, who was aiming to advance a novel drug candidate to help restore the function of BDNF (Brain-Derived Neurotrophic Factor) activity in the Angelman syndrome (AS) mouse model, which is known to be deficient in Angelman syndrome. We are excited to share an update!

Preliminary studies revealed that the limited function of this crucial brain protein, BDNF, could impact the communication between neurons, the synapse, which in turn could have clinical impact on motor coordination, neuronal signaling, and cognitive abilities.

Dr. Marshall and his team previously tested a compound, CN2097, on mice living with AS in hopes to facilitate learning, improved motor function and overall coordination. In AS, the protein BDNF (Brain-Derived Neurotrophic Factor) is not signaling correctly, which is essential for the brain to function well. This is a direct result of a lack of Ube3a protein in the brain. The compound CN2097 targets neuronal tissues and is meant to restore BDNF function. The study also explored a cellular process called autophagy, which is dysregulated in individuals living with AS and can cause excessive breakdown of essential proteins at the synapse that help neurons function. This can also affect synaptic plasticity, cognitive, and motor functions. CN2097 was found to regulate this process, leading to better brain function and improved behavior in the AS mouse model. FAST has now funded this team to take a more translational construct, that has better tolerability and brain biodistribution, with a similar function, to understand a path to potential human clinical trials.

Overall, this compound showed promising results in improving brain function in mice, which may help their learning and memory as well as motor function. This research encouraged further investment into a human candidate drug to potentially improve overall brain function similarly for humans living with AS. 

Dr. John Marshall will be speaking at our Global Science Summit on Friday, November 10th about this new construct and how this can be applicable to our loved ones living with AS! Be sure to register (in person or virtually).