Our Starfish Story
The IFCR has adopted the starfish as the symbol of our organization because it reminds us to keep going and never give up. It was inspired by The Starfish Thrower.
The Starfish Story
About Us
Our mission is to treat and cure CDKL5 Deficiency Disorder by funding scientific research, while helping affected individuals and their families to thrive.
The IFCR is committed to funding scientific and clinical research that will bring about treatments and, ultimately, a cure for CDKL5. We strive to raise awareness of this rare disorder within the medical and lay communities.
Above all, we seek to support all CDKL5 families and caregivers, whether newly diagnosed or well into adulthood, by providing the most current information on treatment advances and how to live their best life possible.
Glyn’s Gift
“Are you sitting down?” These are not words a parent wants to hear in connection to their child but this time they heralded some extraordinary news: “We’ve found your gene.”
CDKL5 Origin Story
Lighting the Way
The International Foundation for CDKL5 Research (IFCR) is proud to be the leading patient advocacy organization for CDKL5 Deficiency Disorder (CDD).
We Are IFCROur History
The International Foundation for CDKL5 Research began as a group of parents whose children had CDKL5 Deficiency Disorder. We came together and dared to dream of a new future for our children. With education and research, we believe that life-changing treatments can be developed.
In 2009, we incorporated the International Foundation for CDKL5 Research as a non-profit organization. Since then, we have funded ground-breaking research and established CDKL5 Centers of Excellence across the United States.
Mission Milestones
2004
Various mutations on the CDKL5 gene are linked to a neurodevelopmental disorder by Dr. John Christodoulou and Dr. Vera Kalscheuer. In separate case-studies, they each link CDKL5 genetic mutations to a phenotype that overlapped with Rett Syndrome.
2009
The International Foundation for CDKL5 Research incorporates as a 501(c)3 organization. We begin as a group of parents whose children have CDKL5 Deficiency Disorder (CDD). A small Yahoo group brings us together and we dare to dream of a new future for our children. With education and research, we believe a life-changing cure will be found.
2010
We fund CDKL5 Knock-Out Mouse Model & CDKL5 Antibody Development with Dr. Cornelius Gross and Elena Amendola, PhD-post doctoral fellow in the European Molecular Biology Laboratory. This effort is in partnership with International Rett Syndrome Foundation (IRSF) and creates the first animal model missing its entire CDKL5 gene, a necessary tool for all drug-development research.
2011
We fund the Knock-In Mouse Model R59X with Dr. Zhaolan (Joe) Zhou at the University of Pennsylvania. This project offers an animal model with an R59X mutation which also provides human samples from a boy and a girl to compare to the mouse. Boys have only one x-chromosome, so this comparison will help us better understand phenotype variations (how CDD affects patients differently).
2012
The International CDKL5 Disorder Database is established as a collaborative effort between the IFCR and Australian researchers, including Drs. Helen Leonard & Jenny Downs.
We host our inaugural International Family Education & Science Conference in New Orleans during the 7th World Congress for Rett Syndrome.
We fund the Identification of CDKL5’s Phosphorylation Targets with Dr. Sila Konur Ultanir at University of California, San Francisco; National Institute for Medical Research, London, UK. This project will help us gain valuable information and a better understanding of the synaptic and molecular functions of CDKL5.
We fund the development of Antibodies Against CDKL5 in the Zhou lab at the University of Pennsylvania. This will help study the function of the CDKL5 protein.
2013
We launch the inaugural multidisciplinary IFCR CDKL5 Center of Excellence at Children’s Colorado with Dr. Tim Benke. This clinic structure will help us establish clinical standards of care and community clinical trial readiness. This effort is in partnership with Rocky Mountain Rett Association.
We co-fund an investigation with IRSF of the Importance of an Uncharacterized MeCP2 Phospho-isoform for Neuronal Morphogenesis and Chromatin Related Functions and the Relationship Between CDKL5 and MeCP2. Dr. Charlotte Kilstrup-Nielsen conducts the research at University of Insubria, Italy. This project will help us understand the relationship between MecP2 (the cause of Rett Syndrome) and CDKL5.
2014
We host the 2nd International Family Education & Science Conference in the Virginia/DC area.
We co-fund the Zhou lab in partnership with the Loulou Foundation. The project explores Modeling CDKL5 Disorder in Mice, including a reversible model, which will help us determine if we can partially or completely reverse any aspects of the disorder.
2015
We fund Uncovering Synaptic Deficits of the Cerebral Cortex Underlying CDKL5 Disorder: The AKT/mTOR Pathway as a Therapeutic Target. The research is conducted by Drs Maurizio Giustetto & Tommaso Pizzorusso at University of Turin & National Institute of Neuroscience, Italy. This research will help us understand if this pathway warrants further investigation for drug development and screening.
We co-fund with IRSF Drug Therapy Targeted to Core Molecules in Neural Plasticity Cascades: A Promising Tool for the CDKL5 Variant of Rett Syndrome, with Drs. Claudia Fuchs & Elisabetta Ciani at University of Bologna, Italy. This research will help us understand if there is a treatment-dependent time frame for the central nervous system to respond to potential treatments targeting CDD (does the age of starting treatment change the success of the treatment).
We fund Neurochemical and Therapeutic Studies in Mouse Models of CDKL5 Disorder with Dr. Wenlin Liao at National Cheng-Chi University, Taiwan. This research will help us understand the relationship CDD plays in certain Autism and ADHD symptoms.
2016
We host the third International Family Education & Science Conference in Chicago.
We establish the St Louis IFCR CDKL5 Center of Excellence at Washington University with Drs. Robin Ryther & Judy Weisenberg.
We fund Investigation of the Role of CDKL5 Expression, Localization and Function in Seizures and Intellectual Disability with Drs. Heather Caballas & Tim Benke at University of Colorado, Denver. This research will help us understand mechanisms that lead to the development of epilepsy and intellectual disability.
We fund the phenotype and behavioral analysis for R59X mouse model at PsychoGenics, Inc. This research will validate this CDKL5 mouse model and make this important research tool available to scientists around the world to consistently study CDD.
We funded Genetic Dissection of CDKL5 Function in Mice with Dr. Zhaolan (Joe) Zhou at University of Pennsylvania. This research will help us identify effects of different types of mutations using several different CDKL5 mouse models.
We participate in the Million Dollar Bike Ride (MDBR) to fund two projects with Orphan Disease Center matching funds. The first is Neurophysiological Correlates in CDKL5 syndrome: a Supplement to the NIH Natural History Study of Rett syndrome, CDKL5 syndrome, and other Rett syndrome-related disorders with Drs. Tim Benke & Eric Marsh at Children’s Hospital Colorado & Children’s Hospital of Philadelphia.
The second is Sensory Evoked Potentials as a Biomarker in CDKL5 with Drs. Charles Nelson, Michela Fagiolini, and Heather Olson at Boston Children’s Hospital/Harvard Medical School. This research will help us better understand longitudinal changes that accompany a CDD diagnosis as a child ages and will support the development of appropriate clinical outcome measures (tools to measure improvement(s) in patients with CDKL5) for future treatment development and trials.
2017
The IFCR welcomes Dr. Heidi Grabenstatter! She joins our team as Science Director and takes the reins in leading our research.
We fund a Zebrafish-based Drug Discovery Program for CDKL5 with Dr. Scott Barbaran at University of California, San Francisco. This research will help us quickly screen large molecule catalogs to search for potential seizure treatments that are already developed and approved for use in humans.
We fund studies of Early Onset Seizures in Mouse Model with Dr. Wenlin Liao at National Cheng-Chi University, Taiwan. This research will help us understand the earliest stages of epilepsy in CDKL5.
We continued our funding of Dr. Zhaolan (Joe) Zhou at University of Pennsylvania for his research into Genetic Dissection of CDKL5 Function in Mice. This research will build on the current work in the Zhou lab developing novel models to understand the potential for reversing or inhibiting the specific aspects of disease progression.
2018
We host our 4th International Family Education Conference in Denver.
We launch the Texas Children’s Hospital IFCR CDKL5 Center of Excellence with Dr. Bernhard Suter.
We launch the IFCR CDKL5 NYU Langone Center of Excellence with Dr. Orrin Devinsky.
We fund CDKL5 Deficiency Disorder: Parental Experience, Phenotyping, and Global Severity Scale with Dr. Scott Demarest at University of Colorado Denver. This research will help doctors better communicate the diagnosis of CDD to families, consistently measure the severity of CDD in the clinical setting, as well as better understand epilepsy phenotypes and progression in CDD.
We fund the Development and Validation of CDKL5 Nanobodies with Dr. Jyothi Arikkath at University of Nebraska Medical Center. This research aims to generate CDKL5 specific nanobodies, a tool that would significantly accelerate our efforts to identify the functional roles of CDKL5 and evaluate how these are altered with CDKL5 disorder mutations.
We fund the R175S and S885 mouse model creation with Dr. Jyothi Arikkath at University of Nebraska Medical Center. This research will provide additional animal model tools with a repeating mutation found in humans.
We participate in MDBR to fund Validation of Pupil Size as a Biomarker for CDKL5 Disorder: Longitudinal Assessment and Relationship with Disease Severity with Dr. Tomasso Pizzorusso, University of Florence, Italy. This research will help us learn the potential to develop a noninvasive tool to screen for, as well as monitor disease progression or improvement in CDD by observing patient pupils.
We also fund Zebrafish as Model to Analyze CDKL5 Function with Drs. M. Leonor Cancela and Marta Vitorino, University of Algarve (UALG) and Centre of Marine Sciences (CCMAR), Portugal. This work will characterize altered behaviors and associated molecular mechanisms in two CDKL5 mutant zebrafish lines to provide a model for screening small-molecule libraries for total/partial rescue of CDD phenotypes.
Recognizing the need for a global patient contact registry managed by the community for the community, IFCR starts “Connect CDKL5.” When someone you love is affected by CDKL5 Deficiency Disorder (CDD), you want to know about every scientific advance and clinical trial that could help them. That is why the IFCR encourages you to participate in our “Connect CDKL5” platform. Be counted with us, because when we band together, we are best able to advocate for our loved ones.
2019
We make a substantial investment in our Centers of Excellence (COEs) that enables the creation of a multi-site IRB and data sharing agreements that link clinical data from our eight COEs and the International CDKL5 Disorder Database to support clinical trial readiness, outcome measure development, and biomarker discovery.
We establish the IFCR CDKL5 UCLA Center of Excellence with Dr. Raj Rajaraman.
We establish the IFCR CDKL5 Children’s Hospital of Philadelphia Center of Excellence with Dr. Eric Marsh.
We fund Early signs of CDKL5 deficiency disorder: developmental trajectory of cerebral cortex maturation and sensorimotor behavioral responses in CDKL5 knock-out mice with Dr. Maurizio Giustetto at University di Torino, Italy. This research will help understand sensory deficits in CDD.
We develop a CDKL5 gene website tool with Dr. Dennis Lal at Broad Institute. This tool displays a graphic of specific mutations based on user input. This tool will give clinicians a visual aide for clinical verification and education. It will also give caretakers a tool to explore the disease-causing mutation specific to their loved one.
We know how important support is for families living with CDKL5 Deficiency Disorder, so we created a peer-to-peer support program with support from Child Neurology Foundation. Our trained Family Support Reps (FSRs) reach out to CDKL5 families and caregivers to offer emotional support and understanding. They also provide helpful resources and can inform caregivers about useful IFCR tools.
2020
We fund Characterization of early neonatal EEGs in R175s and S855 mice and testing seizure susceptibility with Dr. Shilpa Kadam, Associate Professor of Neurology Director of the Pre-clinical In-vivo Electrophysiology Core, Kennedy Krieger Institute
We fund Dr. Dylan Brock, Department of Child Neurology, Children’s Hospital Colorado, Anschutz Medical Campus, to work on Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement
This report summarizes the 2019 Patient-Focused Drug Development Meeting (PFDD) hosted in partnership with the Loulou Foundation in November 2019.
We shift gears from a planned Houston event and virtually host Destination: Cure in a series of pre-recorded and live, interactive educational CDKL5 webinars.
After a collaborative effort to apply for diagnostic recognition, Dr. Eric Marsh makes our case for a CDD specific ICD-10 code. This attempt was successful and code G40.42 was designated for the CDKL5 community.
2021
ICCRN awarded Multi-site validation of biomarkers and core clinical outcome measures for clinical trial readiness in CDKL5 Deficiency Disorder. This project is supported by the NIH-NINDS (U01NS114312-01A1). Validated, standardized COMs will accurately and reproducibly track meaningful changes in clinical trials, ensuring optimal testing of potential new therapeutics, including gene therapy. This work is possible because of the research infrastructure funded by IFCR.
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.
Investigator: Maurizio Giustetto, Univ. of Torino – Dept. of Neuroscience
Seeing the need for a large community awareness and fundraising event, we launch “Move CDKL5 Forward” with a goal of moving 5,000 miles and raising $50,000. Our community smashed those goals and moved over 12,000 miles and raised $153,000 to move CDKL5 research forward! It becomes an annual event that is loved by our community! Find it at CDKL5.com/MOVE
2022
We funded a subset of the ICCRN team to develop a CDD Communication Measure for clinical trial readiness. This qualitative study aims to develop and field test domains of communication specifically for CDD.
There is emerging capability for disease modifying therapies such as gene therapy for CDD and these will be tested in clinical trials in the coming years. However, a critical barrier to strong clinical trial protocols is the lack of a broad complement of validated outcome measures across the spectrum of symptoms, with capacity to demonstrate meaningful interventional changes in how the affected individual feels and functions. There is currently no validated measure for communication in CDD.
Investigator team (alphabetical):
- Tim Benke, MD
Children’s Hospital Colorado, Pediatric Neurology, University of Colorado School of Medicine, Aurora, Colorado - Sofia Benson-Goldberg, PhD, CCC-SLP
Center for Literacy and Disability Studies, Department of Allied Health Sciences, UNC – School of Medicine, Chapel Hill, North Carolina, USA - Scott Demarest, MD
Children’s Hospital Colorado, Pediatric Neurology, University of Colorado School of Medicine, Aurora, Colorado - Jenny Downs, BApplSci, GradCertPubHlth, MSc, PhD,
Telethon Kids Institute, Child Disability, The University of Western Australia, Perth, Western Australia - Peter Jacoby, BA (Hons), MSc
Telethon Kids Institute, Child Disability, The University of Western Australia, Perth, Western Australia - Judy Lariviere, MEd, OTR/L
Assistive Tech 4 ALL, Inc. and consultant Communication Specialist to for Katie’s Clinic for RettSyndrome at UCSF Benioff Children’s Hospital Oakland, California, USA - Helen Leonard, MBChB, MPH
Telethon Kids Institute, Child Disability, The University of Western Australia, Perth, Western Australia - Eric Marsh, MD, PhD
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA - Jacinta Saldaris, PhD
Telethon Kids Institute, Child Disability, The University of Western Australia, Perth, Western Australia - Gina Vander Veen, MPH, CCRP
Children’s Hospital Colorado, Pediatric Neurology, University of Colorado School of Medicine, Aurora, Colorado
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.
Investigator: Michela Fagiolini, Boston Children’s Hospital
Patient data is critical to finding treatments and cures for rare diseases. In 2012, the IFCR partnered with Drs Helen Leonard and Jenny Downs to start the International CDKL5 Disorder Database (ICDD). Information collected in the ICDD was pivotal in defining CDKL5 as a unique disease, and it has led to over 25 important publications that inform how clinicians, parents, and industry understand CDKL5 Deficiency Disorder. We invited Drs Leonard and Downs to a fireside chat to share the history of the database and their collaboration with IFCR, what has been learned, and why family participation in this effort continues to be needed to move CDKL5 research forward. Watch here.
We hosted distinguished CDKL5 thought leaders in Nashville, Tennessee at the American Epilepsy Society (AES) Annual Meeting. The program, entitled “CDKL5 Deficiency Disorder Clinical Research Update” provided attendees with information on the latest in CDKL5 clinical research, including clinical management, special topics, and clinical trial readiness.
Presenters and panelists: Helen Leonard, MBChB, MPH, Tim Benke, MD, PhD, Xavier Liogier d’Ardhuy, PhD, Scott Demarest, MD, Jenny Downs, BAppSci, MSc, PhD, Jacinta Saldaris, PhD, Isabel Haviland, MD, Judy Weisenberg, MD, Heather Olson, MS, MD, Eric Marsh, MD, PhD, Amanda Jaksha, IFCR Board Member, Heidi Grabenstatter, PhD
We continue to invest in CDKL5 clinical research and care to expand our knowledge of this rare disease. Our clinical network is 8 CDKL5 Centers of Excellence strong!
2023
The IFCR began partnering with The Children’s Hospital Montefiore in 2023 to create the Montefiore CDKL5 Center of Excellence. The Montefiore COE is located in the Montefiore Medical Center, Bronx, NY COE. The Montefiore CDKL5 Center of Excellence is located within the Rett Clinic. Dr. Aleksandra Djukic runs the Center.
The IFCR began partnering with Monroe Carell Jr. Children’s Hospital at Vanderbilt in 2023 to create the Vanderbilt CDKL5 Center of Excellence. The Vanderbilt COE is located within the Rett Clinic. Dr. Cary Fu leads a multidisciplinary care team that treats CDKL5 deficiency disorder and other Rett-related disorders as part of their Rett Syndrome Clinic.
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. Read more here.
The initial phase of the ICCRN’s U01 Study had big goals for collecting a robust set of data. Specifically, the goal was to generate, validate, and refine a suite of Clinical Outcome Measures necessary to comprehensively assess disease modification in CDD so we are trial ready. We asked CDKL5 patients to be “1 of 200” – 1 of 200 patients who could be counted as a “complete data set” in this research. A complete data set included visiting one of our US-based CDKL5 Centers of Excellence and participating in clinical exams. It was a big ask, but our CDKL5 community embraced the challenge! To be exact, one hundred forty-three (143!) patients and families! As a rare disease, we shot for the moon with our goal of 200 and landed in the stars with data moving the study onto the final phase! Many thanks to all who participated! Watch a special video explanation here.
Thanks to funding from our sponsors, IFCR hosted seven in-person meet ups for CDKL5 families across the United States! See the recap video here.
We know our website is a lifeline for families, clinicians, and researchers. We invested in a makeover to improve navigation of our site. Special attention was paid to the development of our “Resource Library” which stores our CDKL5 Guides, helpful external links, and video content – all especially curated for families.
2024
We hosted CDKL5 families, clinicians/researchers, and industry partners in Cleveland, OH on June 13-15 for our Keep Rockin’ conference. Held in-person for the first time since 2018, our CDKL5 community was thrilled to gather again to gain the tools and knowledge necessary to care for someone with this rare disease. Sessions were specially curated for families and included education related to common caregiving challenges, the latest in CDKL5 clinical care, and updates on the CDKL5 research landscape. Speakers were leading CDKL5 Deficiency Disorder researchers and clinicians as well as distinguished educators, therapists, and allied health professionals. Watch Conference video recordings on our YouTube channel.
We continue to invest in CDKL5 clinical research and care to expand our knowledge of this rare disease. Our clinical network is 10 CDKL5 Centers of Excellence strong!
More information on the funded research is coming soon!