
Awarded Grants
Awarded Grants
Regulation of CDKL5 Function by Type I Interferons"
Josephine Thinwa, PhD
UT Southwestern Medical Center, USA
$150,000
Awardee: Josephine Thinwa, PhD
Institution: UT Southwestern Medical Center, USA
Award Amount: $150,000
Funding Period: May 1, 2025 - April 31, 2026
Development of a tau hyperphosphorylation assay in CDKL5 deficiency disorder iPSC-derived neurons
Jedd Hubbs, PhD
Boston Children's Hospital, USA
$149,050
Awardee: Jedd Hubbs, PhD
Institution: Boston Children's Hospital, USA
Award Amount: $149,050
Funding Period: May 1, 2025 - April 31, 2026
Exploiting microRNAs to disclose novel pathophysiological mechanisms, biomarkers and therapeutic approaches for CDKL5 deficiency disorder
Maurizio Giustetto, PhD
University of Torino, Italy
$134,300
Awardee: Maurizio Giustetto, PhD
Institution: University of Torino, Italy
Award Amount: $134,300
Funding Period: May 1, 2025 - April 31, 2026
Preclinical Investigations Of Proteasome and Lysosome Inhibitors In CDKL5 Deficient Mice"
James Eubanks, PhD
University Health Network - Krembil Research Institute, Canada
$147,896
Awardee: James Eubanks, PhD
Institution: University Health Network - Krembil Research Institute, Canada
Award Amount: $147,896.00
Funding Period: May 1, 2025 - April 31, 2026
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.
Profiling CDKL5 signaling landscape at the synapses
W. Andy Tao
Purdue University
$150,000
Awardee: W. Andy Tao
Institution: Purdue University
Award Amount: $150,000
Funding Period: May 1, 2024 - April 31, 2025
CDKL5 in Biomolecular Condensates and its Role in CDD Pathophysiology
Keren Lasker
The Scripps Research Institute
$150,000
Awardee: Keren Lasker
Institution: The Scripps Research Institute
Award Amount: $150,000
Funding Period: May 1, 2024 - April 31, 2025
Cortical Visual Impairment in CDKL5 Deficiency: Dissecting the Link between Functional Deficits and Molecular Mechanisms
Jacque Pak Kan Ip
The Chinese University of Hong Kong
$150,000
Awardee: Jacque Pak Kan Ip
Institution: The Chinese University of Hong Kong
Award Amount: $150,000
Funding Period: May 1, 2024 - April 31, 2025
Looking for differences: in vitro isolation of hCDKL5-specific antibody fragments and set-up of a method to quantify hCDKL5 and possibly distinguish between its isoforms.
Ario de Marco
University of Nova Gorica
$150,000
Awardee: Ario de Marco
Institution: University of Nova Gorica
Award Amount: $150,000
Funding Period: May 1, 2024 - April 31, 2025
Integrating Experimental and Computational Approaches to Unravel the Neurophysiological Basis of CDKL5 Deficiency Disorder
Roy Ben-Shalom
UC Davis
$148,442
Awardee: Roy Ben-Shalom
Institution: UC Davis
Award Amount: $148,442
Funding Period: May 1, 2024 - April 31, 2025
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.
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
Therapeutic potential of Ca2.3 inhibitors in CDD mouse and human models
Marisol Sampedro Castanedo, PhD
Francis Crick Institute
$149,942.00
Awardee: Marisol Sampedro Castanedo, PhD
Institution: Francis Crick Institute
Award Amount: $149,942.00
Funding Period: May 1, 2023 - April 31, 2024
New Drosophila models of CDD
Maximo Ibo Galindo
Centro de Investigación Príncipe Felipe
$148,950.00
Awardee: Maximo Ibo Galindo, PhD
Institution: Centro de Investigación Príncipe Felipe
Award Amount: $148,950.00
Funding Period: May 1, 2023 - April 31, 2024
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.
Utilizing patient iPSC-derived neurons to determine the functional consequences of longer cilia in CDKL5 Deficiency Disorder (CDD)
Mustafa Sahin, MD PhD
Boston Children’s Hospital
$149,241
Awardee: Mustafa Sahin, MD PhD
Institution: Boston Children’s Hospital
Award Amount: $149,241
Funding Period: May 1, 2022 - April 31, 2023
Computational drug repurposing for CDKL5 Deficiency Disorder
Diego Di Bernardo, PhD
Telethon Institute of Genetics and Medicine
$150,000
Awardee: Diego Di Bernardo, PhD
Institution: Telethon Institute of Genetics and Medicine
Award Amount: $150,000
Funding Period: May 1, 2022 - April 31, 2023
Rescuing functional defects in a zebrafish model of CDKL5 deficiency: Contribution to the identification of therapeutic target
M. Leonor Cancela, PhD
University of Algarve
$141,338
Awardee: M. Leonor Cancela, PhD
Institution: University of Algarve
Award Amount: $141,338
Funding Period: May 1, 2022 - April 31, 2023
A functional genomics approach to dissect the molecular bases of CDKL5 Deficiency Disorder
Davide Cacchiarelli, PhD
Telethon Institute of Genetics and Medicine
$150,000
Awardee: Davide Cacchiarelli, PhD
Institution: Telethon Institute of Genetics and Medicine
Award Amount: $150,000
Funding Period: May 1, 2022 - April 31, 2023
Hematopoietic stem cell gene therapy as a therapeutic approach for CDKL5 Deficiency Disorder
Joseph Anderson, PhD
University of California, Davis
$150,000
Awardee: Joseph Anderson, PhD
Institution: University of California, Davis
Award Amount: $150,000
Funding Period: May 1, 2022 - April 31, 2023