Awarded Grants

Awarded Grants

MDBR, CDKL5 Million Dollar Bike Ride MDBR, CDKL5 Million Dollar Bike Ride

Investigating Excitation/Inhibition Balance in Cortical-Thalamic Circuitry in CDKL5 Deficiency Disorder Using Human-Derived Assembloids

Francesca Puppo

University of California, San Diego

$61,007

Awardee: Francesca Puppo

Institution: University of California, San Diego

Grant Amount: $61,007

Funding Period: February 1, 2025 - January 31, 2026

Summary:

This project focuses on CDKL5 Deficiency Disorder (CDD), a severe neurodevelopmental condition that causes drug-resistant epilepsy. In CDD, the balance between brain signals that excite and inhibit activity (called the excitation/inhibition or E/I balance) is disrupted, potentially leading to seizures. Cortical-thalamic projections have been implicated with the generation of seizures. However, traditional mouse models have not been able to effectively model the seizure phenotype in CDKL5 deficiency and study the complex interactions between thalamus and cortex. To address this, we will use advanced human-derived models called corticothalamic (CTh) assembloids, which combine brain-like structures (organoids) from patients with CDKL5 mutations. These models allow us to recreate the brain circuits involved in seizures and study how their development is altered. By using cutting-edge technologies such as high-density multi-electrode arrays, calcium imaging, and optogenetics, we can precisely investigate how disruptions in the E/I balance contribute to hyperexcitability in these circuits. Our research aims to identify the key mechanisms behind seizure generation in CDD, paving the way for potential therapies. This study directly supports ongoing efforts to improve CDD disease models and uncover new targets for treatment.

Read More
MDBR, CDKL5 Million Dollar Bike Ride MDBR, CDKL5 Million Dollar Bike Ride

Exploring CDKL5 Impact on Extracellular Vesicle-Mediated Cell-to-Cell Communication: Uncovering Hidden Pathways and Innovative Therapeutic Avenues

Maurizio Giustetto

University of Torino

$60,960.00

Awardee: Maurizio Giustetto

Institution: University of Torino

Grant Amount: $60,960.00

Funding Period: February 1, 2024 - January 31, 2025

Summary:

The main objective of this study is to explore the potential role of CDKL5 in extracellular vesicles (EVs)-mediated cell-to-cell communication and the consequences of CDKL5 mutation. Newly generated data obtained in our lab, thanks to previous financial support from MDBR, disclosed a restricted panel of EV-miRNAs with an altered expression both in CDD patients’ saliva and in murine CDKL5 mutant neurons cultures. Although these findings suggested that CDKL5 is involved in the composition of EVs cargo content, the consequences of these changes are still unknown.

Read More
CDKL5, 2023, CDKL5 Pilot Grant Programme Million Dollar Bike Ride CDKL5, 2023, CDKL5 Pilot Grant Programme Million Dollar Bike Ride

Assessment of the therapeutic potential of TATk-hCDKL5 isoform 1 and 2 produced in recombinant Antarctic Pseudoalteromonas haloplanktis TAC125

Maria Luisa Tutino, PhD

University Federico II of Naples

$149,985.00

Awardee: Maria Luisa Tutino, PhD

Institution: University Federico II of Naples

Award Amount: $149,985.00

Funding Period: May 1, 2023 - April 31, 2024

Read More
MDBR, CDKL5 Million Dollar Bike Ride MDBR, CDKL5 Million Dollar Bike Ride

Choroid plexus disruption in CDD

Michela Fagiolini

Boston Children's Hospital

$50,240.00

Awardee: Michela Fagiolini

Institution: Boston Children's Hospital

Grant Amount: $50,240.00

Funding Period: February 1, 2023 - January 31, 2024

Summary:

In the absence of CDKL5 we discovered a significant disruption of Choroid Plexus (ChP) organization at the level of tight junctions and polarity of selective cellular transporters in the epithelial cells. These preliminary results raise the question whether the loss of CDKL5 negatively affects the function of the blood-cerebrospinal fluid (CSF)-barrier and the composition of the CSF. The ChP-CSF system delivers important growth-active molecules throughout the brain, guaranteeing its proper maturation and functioning. Here we propose 1) a detailed characterization of the development of the ChP epithelial cells in the absence of CDKL5 and 2) a multi-omics approach to profile both CSF and ChP in CDKL5 deficient disorder (CDD) mice. Due to the confined but accessible localization of the ChP, our results may establish the ChP as a new tractable target for CDD intervention.

Read More
MDBR, CDKL5 Million Dollar Bike Ride MDBR, CDKL5 Million Dollar Bike Ride

EXPLOITING NEURONS- AND BRAIN-DERIVED EXOSOMES AS BIOMARKER FOR CDKL5 DEFICIENCY DISORDER

Maurizio Giustetto

Univ. of Torino - Dept. of Neuroscience

$75,000

Awardee: Maurizio Giustetto

Institution: Univ. of Torino - Dept. of Neuroscience

Grant Amount: $75,000

Funding Period: February 1, 2022 - January 31, 2023

Summary:

The identification of objectively measurable parameters is urgently needed to speed up the diagnosis of CDKL5 deficiency disorder (CDD) and to evaluate the outcomes of both pre-clinical and clinical trials. Although exosomes, nanovescicles seceted 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 our proposal is to fill this gap and by establishing and validating a novel molecular, reliable biomarker for CDD patients.

Read More