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Congratulations Dr. Maurizio Giustetto, 2023 Million Dollar Bike Ride Awardee

Heidi Grabenstatter, IFCR Science Director

The Million Dollar Bike Ride (MDBR) is an annual event hosted by the Penn Medicine Orphan Disease Center (ODC). It is an incredible opportunity for rare diseases like CDKL5 Deficiency Disorder because the ODC matches*, dollar‐for‐dollar, the funds raised by nonprofits like ours. It was announced in January that $60,960 was granted to Dr. Maurizio Giustetto to continue his work on CDKL5.

The grant entitled “Exploring CDKL5 impact on Extracellular Vessicle-Mediated Cell-to-Cell Communication: Uncovering Hidden Pathways and Innovative Therapeutic Avenues” aims to elucidate the molecular and cellular pathways underlying neuronal and synaptic abnormalities produced by deregulated miRNAs isolated from CDKL5 knock-out (KO) extracellular vesicles (EVs). In addition, the team proposes manipulation of deregulated miRNAs to rescue synaptic, neuronal and gene expression defects in cortical neurons lacking CDKL5.   

The Giustetto lab has gathered preliminary data demonstrating changes in EV levels from CDKL5 KO neuronal culture and saliva samples from CDD girls.  Additionally, their data shows changes in synaptic morphology and electrophysiological recordings of cells incubated with EVs sampled from WT vs KO.  The goal of these studies is to understand the cargo carried by the EVs that are causing the changes, how they may be used as a biomarker, or potentially used as a therapeutic target. 

Dr. Giustetto and his team was previously funded by IFCR/MDBR in 2021 and this grant aims to continue that work, “Exploiting Neurons – and Brain-Derived Exosomes as Biomarker for CDKL5 Deficiency Disorder.”  The identification of objectively measurable parameters is urgently needed to speed up the diagnosis of CDD and to evaluate the outcomes of both pre-clinical and clinical trials. Although exosomes, nanovescicles secreted by all cell types, can be exploited as unbiased, quantitative and non-invasive biomarker for clinical diagnosis, so far, no information is available on the molecular profile of exosomes in CDD. The goal of the initial proposal was to fill this gap by establishing and validating a novel molecular, reliable biomarker for CDD patients.  The early data that team has gathered is being further pursued in the most recent MDBR award.

IFCR is grateful to Dr. Giustetto and his lab at University of Torino, Italy for their continued commitment to CDD research and the community of families in need of these drug development tools.  We are proud to have a history of working with the dedicated team since initially in 2015, and again in 2019 when they responded to an IFCR Request for Applications and we funded “Early signs of CDKL5 deficiency disorder: developmental trajectory of cerebral cortex maturation and sensorimotor behavioral responses in CDKL5 knock-out mice.” This research will help understand sensory deficits in CDD. 

We want to thank IFCR’s “Team CDKL5 Riding for a Cure,” led by CDKL5 mom Kristin Kozera, for their continued fundraising efforts for MDBR and for getting out to ride year after year. If you’d like to join the ride in June 2024 you can learn more at this Team link or email Kristin (kkozera@cdkl5.com).

You can see all of the past MDBR grants we have awarded for CDD in our Mission Milestones. Have questions about research or want more information? Reach out to Heidi (hgrabenstatter@cdkl5.com).

*MDBR matches funds raised up to a certain amount