A Year In Review: Highlights of 2024

RESEARCH.

Research is the cornerstone of advancing understanding, treatment, and, ultimately, a cure for OCNDS. Supporting scientific studies and data collection helps uncover the mechanisms of the condition and identify therapeutic opportunities.

• SIMONS SEARCHLIGHT – this is our natural history study through the Simons Foundation Autism Research Initiative. They collect family, medical, developmental, and behavioral information. Information is synthesized and results are provided back to families. Data is then shared with qualified researchers. This study is crucial to better understand how OCNDS affects people over time.
• We ended 2024 with:
• 147 individuals registered (+34)
• 141 individuals fully consented (+35)
• 126 individuals with lab reports approved (+35)
• 92 individuals with completed medical history intake surveys (+21)
• This is important as this intake is the main dataset that researchers use to try and better understand OCNDS
• 30 individuals who submitted blood samples (+7)
• These are important as they provide crucial samples for researchers and Simons can generate a special type of cell line, called an induced pluripotent stem cell (iPSC) line from the blood samples
• 109 surveys were completed by participants

• OCNDS PUBLICATIONS
• 2024 ended with 38 (+9) total publications about OCNDS/related to OCNDS
• First foundation publication: Rushing GV, Sills J. Patient organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome. Ther Adv Rare Dis. 2024
• Research explained here
• 1^st mouse model of OCNDS characterized: Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse
• Others publications (linked to the corresponding Research Explained):
• Okur-Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion
• Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur-Chung neurodevelopmental syndrome
• Inherited loss of function variant in CSNK2A1: the oldest reported cases of Okur-Chung syndrome in a single family
• Improvement of variant reclassification in genetic neurodevelopmental conditions
• Expanding the phenotypic spectrum of CSNK2A1-associated Okur-Chung neurodevelopmental syndrome
• Quantifying neurobehavioral profiles across neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders
• Motor phenotypes associated with genetic neurodevelopmental disorders
  

• PLANNING OUR 2025 SCIENTIFIC AND FAMILY CONFERENCE
• July 17-20, 2025
• Location: Embassy Suites by Hilton Denver Central Park located at 4444 N. Havana Street, Denver, CO 80239
• Are you a researcher wanting to attend? Email Dr. Rushing (gabrielle@csnk2a1foundation.org)
• Family registration coming soon!
  
  
• GRANTS
• Applied for 7 highly competitive grants; received 2 grants
• Chan Zuckerberg Initiative Rare as One Cycle 3: $800,000 over 5 years
• 2024 #RAREis Global Advocate Grant: $5,000 to translate key resources for families
• One grant application is pending

• RESEARCH PROJECTS 
• Awarded 1 new research grant:
• Unravel Biosciences – Nasal Swabs from individuals with CSNK2A1 K198R variant
• Aims: They will generate RNA sequencing data from the nasal swabs that will be used to predict drugs and therapeutic mechanisms using the BioNAV™ platform. This will generate the first primary clinical molecular dataset for CSNK2A1.
• Status: Awaiting sample submission from all families. We expect data in Q1 of 2025.

• Fundraised to support 1 new research grant through the Million Dollar Bike Ride:
• Dr. Halim Loukil - Deciphering perturbations of primary cilia in Okur-Chung neurodevelopmental disorder.
• Dr. Loukil will further investigate the mechanisms by which variants in CSNK2A1 affect cilia biology; cilia are important fine hairlike projections from certain cells that have varying functions in our bodies. This project will help researchers better understand what different mutations in CSNK2A1 do in the body and what signaling pathways may be disrupted; this will help the foundation better understand what therapeutic approaches to pursue. 

• Made strides with 3 additional grants funded at the end of 2023:
• Dr. Clement Chow – Drug repurposing screen using OCNDS Fly Model
• Aims: Dr. Chow utilized the Prestwick Chemical Library consisting of 1,520 compounds using a fly model of OCNDS where the levels of CK2 protein are reduced (representing individuals with deletion variants or variants in CSNK2A1 where there is a loss of normal function). Using the fly eye structure as a readout of drug effects, his lab will generate a list of ‘hits’ (compounds) that improve the fly’s symptoms.
• Status: Top 12 hits are being validated. Once complete, we may test compounds in other models (e.g., cell lines, mouse model).

• Dr. Matt Huentelman - Characterization of CSNK2A1 disease causing variants in two-dimensional differentiated neurons
• Aims: Characterize the genotype-phenotype relationship for several disease-causing variants within the CSNK2A1 gene in patient-derived 2D cultures of differentiated neurons generated from induced pluripotent stem cells (iPSCs). This project will be critical in determining the utility of these patient lines for further studies such as drug repurposing and/or gene-modifying therapeutic approaches. Furthermore, we will gain valuable insights into how changes in the CSNK2A1 gene affect development.
• Status: Cell lines received at TGen; some lines successfully growing. Data is expected by the conference in July 2025.

• Dr. Heike Rebholz – Characterization of Mouse Models of OCNDS
• Aims: Characterize four mouse models of OCNDS, whose mutations in the CSKN2A1 gene represent many variants seen in patients. Through this study, the effects of OCNDS will be profiled from a macroscopic to microscopic level, looking for changes in behavior, neuron functionality, and the proteome. This will provide conclusive evidence for the molecular basis of OCNDS and will provide pre-clinical models for testing future treatments.
• Status: K198R mouse line characterized in a publication. A loss of function model (one copy of CSNK2A1 is knocked out) and R47G model currently being analyzed for behavior and function. The 4^th model (R312W) has unfortunately been lost due to unforeseen circumstances with how the model was generated.

• SCIENTIFIC COLLABORATION
• Hosted 4 Scientific Roundtables
• 84 contacts on our scientific roundtable email list
• Met with key CSNK2B researchers at Columbia.
• CSNK2B is the ‘sister gene’ to CSNK2A1; the B gene produces the beta subunit of the protein CK2 whereas A1 produces the alpha subunit.
• Partnered with Citizen Health to provide families with a resource to store all their medical records in one location and participate in optional OCNDS research; we enrolled 62 individuals
• Sponsored Young Investigators with a $5,000 grant to attend the International CK2 Conference in Germany.
• Jose Cruz Gamero of the Rebholz lab in Paris defended his thesis project “Deciphering the role of protein kinase CK2 in a novel mouse model of Okur-Chung Neurodevelopmental Syndrome”.
  

ADVOCACY.

Advocacy plays a pivotal role in championing the rights and needs of individuals with OCNDS. By engaging with policymakers, healthcare professionals, and the broader community, we work to shape policies, raise awareness, and secure necessary resources to improve the quality of life for those affected.

• LETTERS OF SUPPORT
• Signed on to 35 letters of support on various issues important to our community including:
• Increased federal investment in epilepsy research, education about seizure awareness, and funding for clinical trial readiness programs for rare diseases.
• Reauthorization of the Rare Pediatric Disease Priority Review Program, a voucher that the FDA awards to companies that develop therapies for rare pediatric diseases. Priority review means the FDA will act on the application sooner than it would for a regular application.
• Improving cross state access to multi-disciplinary teams of medical specialists in-person for drug administration and other services, as well as through telehealth.
• Encouraging the California Institute for Regenerative Medicine (CIRM) to continue funding research into rare disease biology and treatments.

• RARE DISEASE WEEK
• Jennifer and PAB member Terri Jordan attended Rare Disease Week in Washington, D.C. And meet with representatives from California and Missouri to talk about issues affecting rare disease families. They also attended a brainstorming session to discuss federal legislative language, EPICrd – the Ensuring Parity through Individualized Care for Rare Disorders Act.
• Published & distributed 2nd advocacy one-pager tailored for policymakers.
• Leadership Roles: Jennifer Sills served on the California Coalition for Telehealth for CalRare.
  

AWARENESS.

Awareness is crucial to our mission. Never underestimate the power of knowledge and awareness. With awareness comes social acceptance and kindness, which can mean all the difference to a family struggling with basic daily activities. With awareness comes more funding for research and advocacy. With awareness comes interest from researchers, biotech, and pharma which can lead to a treatment or a cure. And with awareness coupled with action, we are one step closer to understanding and treating OCNDS.

• FDA PATIENT LISTENING SESSION
• We held a listening session on July 23, 2024. This effort was a critical step toward ensuring that the patient and family experience is heard loud and clear by regulatory decision-makers. By sharing our stories and insights with the FDA, we’re paving the way for future advancements in treatment and care.
• Our official summary report captures the experiences of families affected by OCNDS.

• OCNDS AWARENESS DAY
• Over 19 different bridges, places of interest, and monuments around the world lit up in our foundation colors green and blue, including Niagara Falls and High Level Bridge. 
• 6 proclamations were issued declaring April 5^th as OCNDS Awareness Day, including St. Louis County, City of Denver, Nova Scotia, Canada, State of Wyoming issued by the Governor, State of Colorado, City of St. Louis.

• FEATURES. Utilizing a range of media and mediums, OCNDS families and foundation staff have effectively elevated awareness for OCNDS. Through blogs, features in local and national news and articles, participation in podcasts, inclusion in a documentary, and radio appearances, we were able to further broaden the reach of our message. These diverse approaches underscore the significance of tapping into various media channels to cater to different audiences, ultimately fostering a comprehensive understanding of OCNDS and garnering support for ongoing research and support initiatives. Here are some of those highlights:
• Featured blog about the foundation published by the Chicago Council on Science and Technology (C2ST), written by PhD candidate Mackenzie Smith (Loyola University), whom Dr. Rushing met at the Society for Neuroscience Conference.
• Rare Disease Day 2024 reflection by Keri Ninness. Read more here.
• Parent Advisory Board member Claire Whitehill and her family were in the news talking about OCNDS Awareness Day. Read more here. 
• Claire Whitehill worked closely with Genomics England to share her daughter Kirsty’s OCNDS story and the importance of Whole Genome Sequencing. Genomics England is permanently featuring OCNDS and Kirsty’s story on their website. Check it out here. 
• Our very own Amber Reynolds was featured on a podcast from Disability Parenting Pod. From focusing on limitations to celebrating "inchstones," Amber's story reminds us to cherish every small victory in parenting. Listen now here. 
• Jennifer Sills bravely shared her rare disease journey from relief to anger in a blog post. Read her raw & vulnerable piece, "One Foot in Front of the Other: Navigating Anger" here. 
• Episode 4 of the *Dadaptation* podcast featuring one of our own, Brian Reynolds (dad to Harper), is now live on Spotify and Apple Podcasts! Listen on Spotify: https://open.spotify.com/episode/70dyvoewjsElv72jlZRtSa...
• Jennifer Sills has a unique gift for weaving her passions into her advocacy for OCNDS. From her love of movies and sports to her extraordinary storytelling, Jennifer constantly finds creative ways to raise awareness about rare diseases. She occasionally channels that passion to amplify rare disease stories by reviewing films for @theDisorderChannel. Don’t miss her reviews of The Saint of Second Chances on Netflix and One Shot to Live on the Disorder Channel, both featured in RARE Revolution Magazine.

• We earned a 2024 Top-Rated Award from Great Nonprofits for the 3rd year in a row. Read more or leave a review here.
  

FUNDRAISING.

At the heart of every foundation lies the essential truth: it takes financial resources to make a difference. Every dollar raised is a beacon of hope, fueling our mission to bring about meaningful change. From generous donations to grassroots fundraisers, every contribution, no matter the size, plays a vital role in our journey. To all who generously gave or organized fundraisers to support OCNDS research in 2024, we extend our heartfelt gratitude.

• TOTAL RAISED
• We raised over $600,000 through several types of fundraisers:
• Our annual golf tournament in Tarzana, California, at El Caballero Country Club is our largest fundraiser of the year. This year it crushed foundation fundraising records, raising over $430,000 thanks to our 29 volunteers, 123 golfers and sponsors and our outstanding golf committee Jennifer Sills, Micheal Kaplan, Jr., Joey Behrstock, Mike Greenfeld, J. Michael Grossman, Mike Grossman, Connor Hooper, Erin Massey, Avisha Patel, Tracy Phelps. Special thanks to our title Sponsor Pinnacle Contracting Corporation for leading by example.
• Million Dollar Bike Ride: $30,013 with a matching gift of $30,000 from UPENN.
• Run, Walk, & Roll: $23,000. We hosted our 4th annual virtual Run, Walk & Roll event raising over $23,000 with 275 participants across 10 countries.
• Giving Tuesday is a global day of giving and our largest on-line fundraising campaign. For Giving Tuesday, we released a video featuring OCNDS families and researchers; the campaign raised over $112,000 for research, which included a $50,000 matching donation from loyal donors Joan and Charlie Davis.
• In total, our community created 41 Facebook fundraisers!
• Facebook Birthday Fundraisers: $13,288
• Other Facebook Fundraisers: $3,336
• Other Fundraisers: $10,000 (including F45 San Mateo community fundraiser, Terry Jordan & Family Bowling event, The Reynolds Family Brewability Event, Charity Day at BTIG)

• If you are interested in hosting a fundraising event (such as bake sales, garage sales, dine-out nights, fitness challenges, car washes), please contact jennifer@csnk2a1foundation.org to discuss how we can support your event. These grassroots fundraising efforts can engage communities, raise awareness, and make a meaningful impact, one small step at a time.
  

FAMILY SUPPORT.

Supporting individuals and families living with OCNDS is foundational to our mission. This involves providing resources, creating a sense of community, and offering guidance tailored to the unique challenges they face.

• REGISTRY
• In the CSNK2A1 Foundation Contact Registry, we have 291 (+73) individuals from 42 (+8) countries speaking 25 (+3) languages. Our contact registry is one of a kind, as it keeps track of those with OCNDS, even if they speak different languages. This isn’t being done anywhere else. The literature doesn’t represent all the families struggling with OCNDS, and we want to give a better picture of how many people are being diagnosed worldwide. This isn’t a perfect system, as we know many other families that haven’t registered with the foundation for various reasons.  
• It is important for us to collect information about the diversity of mutations as there may be multiple mechanisms causing symptoms in OCNDS; distinct mutations may lead to different symptoms and/or varying severity. The registry also provides us with important contact information to provide families with relevant updates.

• FAMILY MEETINGS
• Hosted 2 regional ambassador meetups (Canada and England) and 7 family zoom calls
• Hosted 2 international family meetings (Paris and London)

• ACCESS TO INFORMATION
• Translated simplified GeneReview into 24 languages
• Part of awareness is arming families with information. In June 2022, Dr. Okur wrote a chapter in GeneReviews about OCNDS. GeneReviews is regarded as a reference resource among geneticists in terms of learning about the scope of a given condition, molecular genetic causes, and surveillance and management guidelines. We created a new resource for families to understand this GeneReview easily and this year we translated this vital resource into 22 languages.
• Hosted a virtual symposium on April 6; YouTube recordings can be found here
• New blog, “Science Snapshots”, aimed at simplifying the complex science and healthcare topics surrounding Okur-Chung Neurodevelopmental Syndrome (OCNDS) and the rare disease community.
• 3 blogs are live on ICD-10 codes and growth hormone
• We developed a new webpage resource where families can nominate doctors who are making a positive impact on the lives of individuals with OCNDS.
• Please continue to tell us about your doctors to help us build a map for people to use as a guide.

• ICD-10 CODE APPLICATION
• Associates at Hogan Lovells submitted our application for an ICD-10 code. Unfortunately, we were not selected for the September review committee meeting. Feedback was encouraging and we expect that our application will be discussed at their next meeting in March 2025.
• An ICD-10 code is important for a rare disease because it creates a standard way for doctors and hospitals to identify and record the condition. This helps with tracking the disease, improving research, and making sure patients can get the care and insurance coverage they need.
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• REGIONAL AMBASSADORS. Regional ambassadors are responsible for building a supportive OCNDS community within their assigned region. They are a liaison between the families and the foundation, identifying issues and challenges that are unique to specific regions. We have 12 regional ambassadors. This year, we welcomed Edouard and Justine Convain. More about our regional ambassadors here.
• Launched a new website making resources more accessible to all OCNDS stakeholders
• Featured 5 Milestone Mondays celebrating the successes of those living with OCNDS. 
• 70 dedicated volunteers generously contributed their time and expertise. These volunteers span the globe, representing regions such as Italy, Brazil, Canada, Texas, Los Angeles, Chicago, New York, San Francisco, United Arab Emirates, United Kingdom, Spain, Netherlands, and Norway.
  

CAPACITY BUILDING & PARTNERSHIPS.

Capacity building focuses on developing the internal structures, skills, and resources necessary for the foundation to grow sustainably and effectively deliver on our mission. Partnerships allow us to work efficiently and achieve more with limited resources. By fostering collaboration, we can influence systemic change, advance research, and bring treatments closer to reality faster than we could on our own.

• We hired Elisabeth Mellinger as our Citizen Health ambassador to help families enroll in this initiative. Having a dedicated person to reach out to families and support them in registering for research projects was crucial to our success in our enrollment numbers.
• We hosted 9 interns for various projects
• Grace Snyder – Masters in Genetic Counseling Student, University of Pennsylvania
• Project: Outreach to genetic testing labs to ensure CSNK2A1 is on relevant panels and generation of resources for families to better understand genetic tests (duration: 4 months)
• Tierney Baum – PhD Candidate, Vanderbilt University
• Project: Research and development focused on finding pharmaceutical and biotechnology partners of interest for the foundation (duration: 4 months)
• Tierney was then hired as a part-time consultant for the foundation to help with scientific writing and additional research projects.
• Elena Bagatelas – PhD Candidate, Vanderbilt University
• Project: Analyzing Simons Searchlight natural history data and publishing results (duration: ~9 months; ongoing until publication acceptance)
• Maahin Manzoor Khan, MBBS (Bachelor of Medicine, Bachelor of Surgery; equivalent to the Doctor of Medicine [MD] degree in the U.S.) - Shifa College of Medicine
• Project: Along with Elena and Dr. Rushing, analyzing Simons Searchlight natural history data and publishing results (duration: ~9 months; ongoing until publication acceptance)
• Aryana Adeline Valle-Portela – Undergraduate Student, University of California, Berkeley
• Project: Assisting the foundation with social media presence and interviewing families to collect their stories (duration: 8 months).
• Grace Branger – Masters in Genetic Counseling Student, Vanderbilt University
• Project: Grace will be collaborating with the CSKN2A1 Foundation and COMBINEDBrain to develop a disease concept model for OCNDS, aiming to highlight the lived experiences of affected individuals and their families (duration: 2 years, started August 2024, ongoing). This research will inform clinical trial endpoints that prioritize patient and family needs.
• Monica Strain – PhD Candidate, University of Connecticut
• Project: Scientific Resource Development Intern. Monica will be developing comprehensive lists of resources such as grants, conferences, and research tools that scientists may find valuable for research in epilepsy, autism, rare disorders, neuroscience, and related topics. She will also attend a monthly meeting with scientific staff from other rare disease patient organizations (duration: 4-6 months, ongoing).
• Caroline Bodnya – PhD Candidate, Vanderbilt University
• Project: Caroline is our 2025 conference intern. She will be helping with planning the conference and will be on-site to write conference summaries (duration: 9 months, ongoing).
• Ingrid Vallee, PharmD- PhD Candidate, Scripps Research
• Project: Science Communications Volunteer. Ingrid will apply her pharmacy degree to assist with writing blog posts for our new Science Snapshots blog feature (duration: 4 months, ongoing).

• Jennifer Sills stepped into her new role as Co-Chair of the CombinedBrain Board of Directors. CombinedBrain is a consortium of neurodevelopmental Patient Advocacy Groups accelerating treatments by pooling data.
• ATTENDANCE AT CONFERENCES
• Dr. Rushing attended 8 conferences spanning neuroscience, patient advocacy, and drug development. She received travel awards for 3 of these conferences.
• Dr. Rushing served as a moderator for 2 conferences (National Organization for Rare Disorders and Global Genes Rare Drug Development Symposium).
• Dr. Rushing also represented us as a continued member of the Epilepsy Research Benchmarks Stewards Committee.
• Brought on Tierney Baum, PhD, as a project research consultant to strengthen our research capabilities.
• Dr. Rushing stepped into her new role as Chief Science Officer.
• Increased the hours of our Operations Manager, Beth Chaffin, to better support the growing needs of the foundation and ensure smooth day-to-day operations as our reach and impact continue to expand.
• 3 new partnerships (Citizen Health, CZI and FasterCures’ The Research Acceleration and Innovation Network (TRAIN))
• 22 existing partnerships continued
• We held 6 Parent Advisory Board meetings in which 11 parent advisory board members played a vital role in ensuring the patient voice is heard and represented in all aspects of our foundation.
  

By the Numbers