CDKL5 and Gene Therapy

A rare genetic disease caused by mutations or deletions of the cyclin-dependent kinase-like 5 (CDKL5) gene, CDKL5 deficiency disorder (CDKL5) causes symptoms including developmental delay, epilepsy, sleep issues, and more. All though some supportive care for the devastating disorder is available, there is currently no cure.

CGTLive® interviewed Jainu Jogani, the cofounder of Child’s Cure Genetic Research, whose daughter Reyna has CDKL5, at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, LA. In the discussion, Jogani explained what CDKL5 is and how it affects patients and their families. He also went over the currently available treatment options and potential future treatment options for the disorder, highlighting a preclinical gene therapy program he and his team are currently working on.

CGTLive: Can you introduce yourself?

Jainu Jogani: My name is Jainu Jogani. I am the father of Reyna. She's 7 years old. She's impacted by the CDKL5 disorder.

Can you give some background context about CDKL5?

CDKL5 is a rare genetic disorder. When Reyna was 20 days old, she started having random hand and eye movements, which initially were 2 or 3 seconds long. They were very difficult to be captured so we started 24 hour monitoring, and as soon as we sent one of the recordings to the doctors, the next thing we know is we got a call from the hospital, and they asked us how soon we can get to the hospital. We took Reyna in. They did EEG, they did the MRI, they did lots of blood work. The EEG came up abnormal, and it indicated epileptic wave forms, but the blood work and the MRI came up normal. And then they sent out blood work for the epileptic panel, and it came for CDKL5. Then my wife's and my blood were analyzed and we were not carriers for it, meaning that this is a de novo mutation, so it's not hereditary.

CDKL5 is a genetic mutation. Reyna has a 10 kb deletion on exon 1 of the CDKL5 gene. This gene makes a protein. This protein has important functions, as we are learning, throughout the body, but the most important functions are in the brain and across the neurons. This protein is a regulatory protein, and because of lack of this protein, transmission of signal across the neurons doesn't happen properly, and this excessive energy is dissipated in the form of seizures and other ways. Reyna has a developmental delay. She's 7 years old, and she's not walking or talking yet, and there is a wide variety of symptoms, like GI and sleep issues and breathing issues associated with this disorder. It is very devastating. The child is completely dependent on the caregivers, their family. Some children have up to 40 seizures a day. Just to see children have so many seizures is disheartening for the family.

What does the current available treatment for CDKL5 look like?

The current treatment options include antiepileptic medicines. The epilepsy aspect with CDKL5 is classified as intractable, meaning that it is very difficult to control the seizures and usually with each new AED that a child starts, there is a few days of seizure control that they would see, and then the child would go back to having the same seizures. So there aren't many effective treatment options, and we families excessively rely on physical therapy, occupational therapy, speech therapy, vision therapy, hippotherapy, swimming/aquatic therapy, and all these alternated modalities to improve the quality of life of the children. There is not a cure for this disorder yet.

Are there any new treatments currently in development?

There are a lot of exciting things going on. We are working on AAV9-based gene therapy. There's a lot of preclinical work that has been done, and now we are getting ready to submit the preIND for those.

Along with that we have found a paralogue gene to CDKL5. My daughter basically has a genetic deletion so even if through drug repurposing we would have boosted the activity of CDKL5, in her case, it wouldn't work because anything multiplied by zero is still zero. So what we did instead was we targeted CDKL2, a paralogue gene. We found an FDA approved medicine that targets this gene, and from there, we get a little help. From the development mechanism, we know there is 33% overlap in CDKL2 and CDKL5. So from that perspective, we know there is this small molecule, this already FDA-approved drug that is working for her and other children that are taking this medicine. We are also working towards starting a clinical trial with John Hopkins for this.

So gene therapy is there, we have the small molecule, and there are other exciting projects also that we're hoping will go from the preclinical stage to the clinical stage for CDKL5.

What would you say is your main takehome message to the broader healthcare community?

The medical community, the doctors and all the scientists and researchers, are doing a phenomenal job, especially in the rare disease world, so I ask them to please keep it up. There is this sense of urgency that comes with rare disorders. Many in the industry understand this. It would be phenomenal if everybody could understand this and give support at that level and with that sense of urgency, so that we don’t have to wait the traditional 7 or 10 or 15 years for development of a medicine for our children. So that would be my request.

Is there anything else you want to add?

When we got Reyna's diagnosis we were totally devastated, and we didn't know what to do, but there are resources around you. There is lot of help available. So please ask. Please reach out. Everybody is here to help you. You need to ask the questions and advocate for your child. You're not alone in this journey, and please don't take no for an answer from the doctor or the clinician who initially sees you. There is so much more out there so please be the best advocate for your child.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.