At the IFCR’s 6^th CDKL5 Family Education & Awareness Conference this past June, attendees heard Scott Demarest, MD, Children’s Hospital Colorado, share the latest update on the important work being done by the International CDKL5 Clinical Research Network (ICCRN) through their NIH-NINDS funded U01 grant “Multi-site validation of biomarkers and core clinical outcome measures for clinical trial readiness in CDKL5 Deficiency Disorder.” 

What does it mean to treat CDD? 

It means treating the root of the problem, not the symptoms. Calling this “disease-modifying,” Dr. Demarest described the future of treatments as ideally improving as many symptoms as possible, improving functioning and development, and improving quality of life. 

He discussed therapeutic target possibilities for neurogenetic diseases including those that target DNA, RNA, and protein, all of which have their own advantages and drawbacks and are in different stages of development. 

It’s like the first iPhone model. 

“It’s an exciting time for new treatments of genetic conditions!” exclaimed Dr. Demarest to the audience, but with the caveat that this technology is in its infancy. Much like the original iPhone model, he said, it will need time to become more sophisticated. 

What is clinical trial readiness? 

While we wait for disease-modifying treatments, the CDKL5 community is already at work preparing for their arrival by getting CDKL5 clinical trial ready. But what does this mean? 

Dr. Demarest shared simply – clinical trial readiness is important so that the results of a trial are accurate. If a drug works but we don’t capture it, it is the same as the drug not working and won’t get approved by the FDA.

Researchers need to know what symptoms are meaningful to measure, be able to measure them consistently and accurately as well as understand them over time. To do this, they utilize what are called outcome measures and the ICCRN is working through a development and validation pipeline that aims to create outcome measures for CDD. 

Not only outcome measures, but biomarkers are also part of the team’s research. At some sites, ICCRN researchers are looking to identify brain activity biomarkers of disease evolution and severity using evoked potentials (flashing lights and sounds) and resting EEG. 

What is there to celebrate? 

During his update on the study progress, Dr. Demarest reminded the audience of the success of the initial phase of the study. 143 CDKL5 patients were counted as complete datasets after visiting a CDKL5 Center of Excellence in the US. The knowledge learned allowed the team to refine measures to improve accuracy and reliability. He shared that feedback from industry external advisors was exceedingly positive. 

The ongoing longitudinal phase of the study aims to validate the clinical outcome measures and biomarkers over time. This is a heavy lift for participating families with many site visits and questionnaires to complete. But one thing is clear – CDKL5 families are motivated to do whatever they can in hope of a healthier future for their children! 

Let’s celebrate: 

• 184 unique participants (more internationally)!
• 483 clinical exams with new instruments!
• 246 fine and gross motor video recordings! 
• 170 EEGs!
• 4,076 parent questionnaires completed!

Yes, that is over 4,000! 

4,076 parent questionnaires covering symptom severity, development, sleep, communication, quality of life, function, and demographics. What an achievement! 

The ICCRN is working hard to get CDKL5 clinical trial ready, but their work is only made possible by the ongoing contributions of the CDKL5 patient community. Their dedication is paying off and we look forward to additional updates to come!