CCC-Funded Research

Kasri Lab       Mefford Lab     Rubinstein Lab    Willsey Lab

A major aspect of CCC's mission is to identify and fund relevant CHD2 research that advances our understanding of CHD2 haploinsufficiency and helps pave the way for targeted therapeutics. Since 2022, CCC has invested nearly $200,000 in CHD2 research.

2025-2026 | Kasri Lab

Radboud University Medical Center | The Netherlands

CCC provided funding to Prof. Dr. Nael Nadif Kasri and Dr. Elly Lewerissa to develop a patient-specific platform to understand the condition better and guide more targeted treatment strategies. The team is using cells derived from individuals with CHD2 mutations to generate human neurons in the laboratory. These neurons are cultured on advanced microelectrode arrays (MEA) chips, which enable real-time monitoring of their electrical activity. This “brain-on-a-chip” system provides a powerful tool to study how patient-specific neural networks function and respond to various anti-seizure medications.

We hope this will:

• Validate a testing platform that uses CHD2 patient-derived brain cells to study potential treatments.
• Measure whether a treatment works by checking how the brain cells’ electrical activity changes in response to different therapies.
• Test antisense oligonucleotides (ASOs) to see if they can correct or improve CHD2-related brain activity, which could help move this approach toward clinical trials.
  
  

2024-2025 | Mefford Lab

St. Jude Children's Research Hospital | United States

CCC awarded Heather Mefford, MD, PhD with a 2024 Rare Epilepsy Partnership Award to advance treatments for CHD2-related disorders, in collaboration with CURE Epilepsy. Dr. Heather Mefford's lab at St. Jude Children’s Research Hospital is conducting research to investigate the methylation signature of CHD2-related disorders.

We hope that CHD2 methylation signatures will:

• help clarify variants of unknown significance diagnoses and/or
• predict symptoms and traits associated with CHD2

2022-2023 | Rubinstein Lab

Tel Aviv University | Israel

CCC and others provided funding to Moran Rubinstein, PhD's laboratory to develop a mouse model of CHD2 hapolinsufficiency to be used to test targeted therapies.

Scientists discovered that, by changing the genetic background of the mice from black-coated to white-coated strain, they were able to unmask key disease-related traits. White-coated mice that were genetically modified to have CHD2 haploinsifficiency showed growth delays, motor defects, autistic-like behaviors, altered brain activity, and increased seizure susceptibility, making them a much better model of CHD2-related disorders. Importantly, the study also identified a gene called KCNJ11 as a potential genetic modifier. This gene is already known to play a role in brain function, and mutations in KCNJ11 have been linked to developmental delays, epilepsy, and neonatal diabetes.

Why this is important:

This new mouse model is a crucial step forward in CHD2 research. It provides a powerful platform for studying the disease in greater detail, testing existing treatments, and developing new therapies. Additionally, understanding how genetic background influences symptom severity may help explain why some children are more affected than others, opening the door to future treatments that target these modifying genes. This discovery brings new hope to families affected by CHD2-related disorders, paving the way for better research and potential treatments.

Preprint here

2022-2023 | Willsey Lab

University of San Francisco | United States

CCC provided funding to Helen Willsey, PhD to study CHD2 in Xenopus (frogs).  Dr. Willsey and her team found that CHD2 may play an important role outside the nucleus, on microtubules, and may be localized to another microtubule-rich structure, cilia. Cilia are very important in epilepsy and intellectual disability.

Why this is important:

This is the first time the role of CHD2 has been studied outside of the nucleus; this study increases our understanding of CHD2 and CHD2-related disorders. If there are any CHD2 patients in the San Francisco area please contact us if you are willing your CHD2 loved one to undergo a nasal cilia test to help correlate the findings.