Our Mission
IDefine is a nonprofit organization dedicated to discovering life-changing treatments and cures for those with intellectual disabilities stemming from genetic disorders.
We plan to discover and bring to market life-changing treatments for Kleefstra Syndrome patients. In doing so, we will demonstrate that Intellectual Disability (ID) disorders are in fact treatable conditions, in the same way that disorders of mental illness have become treatable with drugs over time.
Kleefstra Syndrome is an excellent model system for drug development in the ID space:
- A single gene causes KS (EHMT1), and it has been extensively studied
- There has already been substantial scientific research on the underlying mechanisms of KS, and there is a highly active community of researchers
- EHMT1 is involved in epigenetic regulation, an area of research that has seen substantial investment and drug development in the last decade
- Epigenetic regulation appears to be a key factor in multiple ID syndromes, so development of a treatment for KS may inform options for other syndromes
- There is a very active community of KS families, opening the door to clinical study recruitment when a potential therapy has been identified
Kleefstra Syndrome is an excellent model system for drug development in the ID space:
- A single gene causes KS (EHMT1), and it has been extensively studied
- There has already been substantial scientific research on the underlying mechanisms of KS, and there is a highly active community of researchers
- EHMT1 is involved in epigenetic regulation, an area of research that has seen substantial investment and drug development in the last decade
- Epigenetic regulation appears to be a key factor in multiple ID syndromes, so development of a treatment for KS may inform options for other syndromes
- There is a very active community of KS families, opening the door to clinical study recruitment when a potential therapy has been identified
In consultation with our Scientific Advisory Board, we will pursue the most promising avenues for drug development, and “go where the science takes us”. A range of approaches are being reviewed, including small-molecule drug repurposing, small molecule drug development, oligonucleotide-based therapies, or gene therapies.
Scientific Advisory Board
Eric Scheeff
Eric, Isaac’s father, is a scientist and software professional with more than 20 years of experience spanning molecular biology, bioinformatics, and genomics.
Eric Scheeff
Eric, Isaac’s father, is a scientist and software professional with more than 20 years of experience spanning molecular biology, bioinformatics, and genomics. He received his Ph.D. from the University of California San Diego (UCSD) and performed original research at UCSD and the Salk Institute. He has authored numerous research articles, many of which are highly cited in their fields, as well as several book chapters.
Eric pairs this rich scientific research background with substantial experience in the business world, including roles in product development, sales, and marketing. He has focused his career on delivering software solutions to researchers that help enable them to make the next round of scientific discoveries. He is currently the global Product Manager for Biological Interpretation at Illumina, the world’s leading genomics company. There he helps guide the development of Illumina’s software solutions for downstream interpretation of genomic data.
Eric happened to sit next to Darrick at the Kleefstra Syndrome family conference hosted by Kid’s IQ Project, and they hit it off immediately and exchanged phone numbers. Some months later Eric received a message from Darrick about the concept of IDefine. His simple reply was, “Sounds great. I’d like to get involved.” He is delighted that he can leverage his background to help this remarkable team develop a vigorous research program focused on finding new life-changing treatments.
Paul Smith
Paul, Edward’s father, is an accomplished pharmacologist with extensive pharmaceutical industry experience across all phases of the R&D process.
Paul Smith
Paul, Edward’s father, is an accomplished pharmacologist with extensive pharmaceutical industry experience across all phases of the R&D process. Dr. Smith received his Ph.D. in Immunology and Neuroscience at Imperial College London, UK and a B.Sc. in Pharmacology from the University of Bath, UK. Dr. Smith has more than 15 years of drug discovery experience primarily focused on the treatment of inflammatory and autoimmune diseases, and he is an inventor on fifteen issued or pending patents. He is currently the Vice President of Discovery Biology with Connect Biopharma. Prior to his career with Connect Biopharma, Dr. Smith was Senior Director of Inflammation and Autoimmunity at Incyte Corporation where he established the discovery research team.
Paul, the initial member of IDefine’s SAB, feels right at home in his position on the SAB. “I’m not just a guy on a scientific advisory board helping out with some scientific questions,” Paul said. “I’m a parent, I see Eric and Geoff as my friends, and I see them as people with a common goal and an infectious energy. I want to be working with them, it’s not an obligation.”
Prof. Tjitske Kleefstra
Dr. Kleefstra and her research team identified the genetic cause for the set of characteristics associated with what is, after her work, known as Kleefstra Syndrome.
Prof. Tjitske Kleefstra
In 2010, Dr. Kleefstra and her research team identified the genetic cause for the set of characteristics associated with what is, after her work, known as Kleefstra Syndrome (KS).
Dr. Kleefstra continues her work to improve diagnostics, management and treatment for patients with neurodevelopmental disorders, particularly those resulting in intellectual disabilities. She leads a research team focused on developing individual approaches to treating and managing these disorders, working to construct personalized healthcare for patients diagnosed with rare conditions.
Dr. Kleefstra remains an active participant in the KS community, building bridges between researchers and the families affected by KS and other intellectual disabilities. She provides monthly updates to the IDefine team and their colleagues, ensuring access to the latest scientific developments in her work. She sees great potential in IDefine’s capacity to bring teams of scientists and doctors together to work toward funding research and clinical trials for life-changing treatments and therapies for those diagnosed with KS.
“It is a great honour for me to highlight the launch of IDefine, the first US based, but globally supported, charity focused on fundraising for research on the Kleefstra Syndrome!
The syndrome that I, together with my colleagues in Nijmegen, The Netherlands, study intensively after we identified 15 years ago the causal genetic factor: the EHMT1 gene!
Only by joining world-wide efforts can we move this field on a RARE disorder forward to challenge the various aspects we all face.
It is difficult to foresee where we are in another 15 years, but we may expect huge steps that now only seem magic!
Thanks to all who made IDefine possible and looking forward to a well connected future!”
Alysson Muotri
Dr. Muotri is a professor at the Departments of Pediatrics and Cellular & Molecular Medicine at UC San Diego.
Alysson Muotri
Dr. Muotri is a professor at the Departments of Pediatrics and Cellular & Molecular Medicine at UC San Diego. He is also the Director of the Stem Cell Program and Archealization Center at UCSD. Dr. Muotri earned a BSc in Biological Sciences from the State University of Campinas in 1995 and a Ph.D. in Genetics in 2001 from University of Sao Paulo, in Brazil. He moved to the Salk Institute as Pew Latin America Fellow in 2002 for a postdoctoral training in the fields of neuroscience and stem cell biology. His research focuses on brain evolution and modeling neurological diseases using human induced pluripotent stem cells and brain organoids. He has received several awards, including the prestigious NIH Director’s New Innovator Award, NARSAD, Emerald Foundation Young Investigator Award, Surugadai Award, Rock Star of Innovation, NIH EUREKA Award, Telly Awards among several others.
Steven Gray
Dr. Steven Gray earned his Ph.D. in molecular biology from Vanderbilt University in 2006, after receiving a B.S. degree with honors from Auburn University. He performed a postdoctoral fellowship focusing on gene therapy in the laboratory of Jude Samulski at UNC Chapel Hill. He is currently an Associate Professor in the Department of Pediatrics at the University of Texas Southwestern Medical Center. Dr. Gray is the director of the UTSW Viral Vector Facility and maintains affiliations with the Department of Molecular Biology, the Department of Neurology and Neurotherapeutics, the Eugene McDermott Center for Human Growth and Development, and the Hamon Center for Regenerative Science and Medicine at UT Southwestern. Dr. Gray’s core expertise is in AAV gene therapy vector engineering, followed by optimizing approaches to deliver a gene to the nervous system. His research focus has also included preclinical studies to development AAV-based treatments for neurological diseases, some of which have translated into clinical trials.
Dr. Nael Nadif Kasri
Dr. Nael Nadif Kasri, is a neurobiologist who has extensive experience with the molecular mechanisms underlying synaptic plasticity.
Dr. Nael Nadif Kasri
Dr. Nael Nadif Kasri, is a neurobiologist who has extensive experience with the molecular mechanisms underlying synaptic plasticity, including imaging and electrophysiological methods in cellular and animal models. Since the start of his postdoctoral studies he has been interested in understanding the molecular mechanisms of neurodevelopmental disorders. In his postdoc he mainly focused on understanding the function of Intellectual disability (ID) genes related to the RhoGTPase pathway and he was among the first to posit that ID disorders are disorders of the synapse.
When starting his lab in 2011 at the Radboudumc, he joined the Human Genetics department (Nijmegen, the Netherlands) where he started several collaborations to understand the synaptic basis of ID. As such he has focused his research on several syndromes that were initially discovered in Nijmegen, being Kleefstra syndrome and Koolen-de Vries Syndrome. One of his recent contributions is the implementation of multi-electrode recordings in human induced pluripotent stem cells. This technique enables the stratification of patients who suffer from autism, which may lead to more specific therapies.
Dr. Nael Nadif Kasri was awarded with a Human Frontiers fellowship at Cold Spring Harbor Laboratories (USA), where he performed his second postdoctoral study. Since 2011 he has his own research group at the Radboudumc, and became part of the Donders Institute in Nijmegen, the Netherlands. There he was granted a prestigious Hypatia fellowship and a Marie Curie Career Integration Grant.
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Natural History Study
Investigating the Natural History of Kleefstra Syndrome
We are conducting an international research study for individuals’ ages 13 years and older diagnosed with Kleefstra Syndrome. The goals of this research are to study the natural history of Kleefstra Syndrome and determine best practices for treating the mental health challenges such as psychosis and behavioral regression that can be associated with Kleefstra Syndrome. Who can participate in this study?
Participants that are genetically diagnosed with Kleefstra Syndrome (EHMT1 deletion or pathogenic variant) and are 13 years or older.
How long will the study last?
- This will be a 4-year natural history, observational study. You will be asked to visit a site at least 4 times during the study or you may participate through a yearly virtual study visit.
What will participants do during this study?
- Participant/caregiver will need to sign an informed consent form which will go over the study in detail and ensure understanding
- Participants will have behavioral and cognitive testing, physical exams and blood tests (for safety)
- Parents/caregivers will answer questions about the participant’s behavior and medical history
- If participant shows clear signs of psychosis or a deterioration in behavioral functions we may ask the participant to come in additional times
Radboud University Medical Center: joost.kummeling@radboudumc.nl
Manchester Centre for Genomic Medicine: Siddharth.Banka@mft.nhs.uk
Boston Children’s Hospital: KleefstraSyndromeClinic@childrens.harvard.edu
If you fall outside of the study’s scope, please contribute by submitting this survey:
Kleefstra Survey
Radboudumc in Nijmegen is constantly collecting data from people with Kleefstra syndrome, in order to learn more about this rare disorder. Since there are many people around the world that we can learn from, the medical center has put together a survey.
Our Projects
We would love to hear from you.
If you have any questions feel free to contact us. We will be sure to get back to you as soon as possible.