Frequently Asked Questions

No, the gene replacement therapy is designed to deliver a functional copy of the CDKL5 gene to restore protein expression, making it suitable for most loss-of-function mutations rather than being mutation-specific. It aims to address the underlying deficiency broadly across patients.

Based on preclinical data showing phenotypic rescue in mouse models and positive FDA feedback, confidence is around 7-8, reflecting optimism from safety profiles and efficacy in animals, though human trials introduce uncertainties.

IND approval estimated mid-2026, with first-in-human dosing potentially starting late 2026, though timelines depend on toxicology results and FDA review.

Approximately $3.5 million is needed to advance to first-in-human trials, covering toxicology, manufacturing, and IND submission.

Funding relies on donations and grants to reach $3.5M for trials; current efforts include community fundraising and potential pharma collaborations. Please donate via CDKL5GeneTherapy.com and share with others.

Eligibility will be based on confirmed CDKL5 mutation, age, health status, and trial criteria (e.g., no contraindications to AAV9); more information for screening will be made available once IND is approved.

Yes, international participation is possible, with trials planned in the US and India; visa and travel support may be available, subject to regulatory approvals.

Preclinical data suggest earlier intervention (neonatal or early childhood) maximizes benefits due to brain development stages, but studies show potential rescue even in older models (equivalent to adulthood), so no strict cutoff, though younger ages may yield better outcomes.

Yes, but more details will be available shortly based on inclusion/exclusion criteria after the IND.

Contact trial sites (e.g., UCSF, Boston Children's) for pre-screening; once trials start, eligibility will be assessed based on inclusion criteria.

The CDKL5 Gene Therapy Coalition (via cdkl5genetherapy.com) for direct support of this AAV9 program, as it focuses specifically on advancing this gene therapy initiative.

Directly through cdkl5genetherapy.com.

Donate via cdkl5genetherapy.com; help by spreading awareness, participating in registries, or volunteering for advocacy to accelerate progress.

Yes, the webinar is posted on the CDKL5genetherapy.com website under past webinars section.

Yes, patients can register on www.cdkl5genetherapy.com, which helps with eligibility screening and data collection for CDKL5 studies.

The therapy restores CDKL5 protein to promote synaptic maturation and neuronal connectivity; in preclinical models, it rectifies stunted growth even post-development by enhancing microtubule dynamics. Reinforcement may involve therapies like physical/occupational to maximize gains, similar to other neurodevelopmental treatments.

Yes, Rett Syndrome gene therapy trials (e.g., Taysha's TSHA-102, Neurogene's NGN-401) show improvements in motor function, seizures, and behavior in early data; details available on ClinicalTrials.gov or RSRT.org, with some patients gaining skills like hand use.

Pigs provide a crucial bridge between small-animal studies and humans. A pig's brain is much larger than a rodent's and is closer to the size of a young child's brain. It has similar folds (gyri) and a comparable mix of white and gray matter as humans. Pigs also have cerebrospinal fluid (CSF) volumes and blood–brain barrier properties that match humans when scaled for body size. These features let us test how our gene therapy distributes in a brain and body that behave more like those of a patient especially for route-of-administration, dosing-volume, and CSF dynamics assessments. We can even use clinical imaging (like MRI) and collect fluid or tissue samples from pigs, making safety and dosing tests very realistic.

Models that reproduce key human symptoms (for example spontaneous seizures) give much stronger evidence that a therapeutic effect is likely to translate. Rodents are essential for mechanism and screening, but some rodent models do not reliably reproduce spontaneous seizure phenotypes seen in patients; a large animal that can help resolve questions about dosing, distribution to relevant brain regions, and potential on-target/off-target effects in a brain more similar to humans. Because the blood–brain barrier (BBB) and CSF flow can change with CDKL5 disorder, testing in a symptomatic large animal helps reveal issues that simple healthy-animal studies might miss.

Yes — recent tragic events in other AAV trials underscore why robust, multi-species preclinical data and careful clinical design are essential. We monitor those cases closely (e.g., the recent Capsida trial report) to learn root-cause lessons and to update our safety plans, monitoring, and stopping rules accordingly. These events reinforce the need for careful dose selection, thorough biodistribution and toxicology, and independent safety oversight.

Rodents are useful for early research, but they don't show spontaneous seizures like CDKL5 patients and their brain physiology often differ from humans. Many mouse models of CDKL5 have engineered mutations or induced seizures that do not fully match the unpredictable, ongoing episodes seen in patients. Our large pig model naturally exhibits seizures similar to the human condition. Testing our therapy in this pig means treating a brain already in a diseased state. In this setting we can see whether the gene therapy reduces seizure frequency or causes any unexpected effects in a brain prone to seizures, which is closer to how the therapy would act in a child.

A diseased brain can also change how treatments spread. Seizures and neurodevelopmental disorders can alter the blood–brain barrier (the brain's protective filter) and cerebrospinal fluid (CSF) flow. For example, repeated seizures can make the barrier more permeable. Because our pig's brain and CSF volume are similar to a human child's, we can measure exactly where and how much therapy enters the brain.

The recent Capsida trial tragedy (a patient death after an IV AAV gene therapy) underscores why this modeling matters. That trial required the vector to cross the blood–brain barrier through the bloodstream, and investigators are still evaluating what happened. Our pig study lets us mimic similar delivery conditions in a controlled way. If ICM delivery triggers issues (such as excessive inflammation or organ stress), our pig data will reveal warning signs early. We can then adjust our approach (dose, delivery route, patient criteria) to avoid problems before moving to clinical trials.

A symptomatic large-animal model makes preclinical testing much closer to the human condition. It includes key disease features (like spontaneous seizures and altered brain barrier conditions), allowing us to spot and reduce risks early and design a safer, more effective therapy for patients.

Our research is still in preclinical stages, so it is still being worked on to be published. However, it is far from unexamined. We have a rigorous review process at every step. Internally, our scientific team analyzes and validates each finding. Externally, we collaborate with independent experts and regulators. For example, we have held pre-IND discussions with the FDA, where we presented our safety and efficacy data and received detailed feedback. We also consult with pediatric neurologists and rare-disease specialists who provide independent critique and guidance. In short, professionals with deep expertise evaluate our data long before we finalize any trial plans.

AAV9 (and related AAV serotypes) has a substantial clinical track record but also known class risks that require careful management. The most prominent approved AAV9 therapy is ZOLGENSMA® for spinal muscular atrophy (SMA); thousands of patients have already received AAV9 under medical supervision. Its regulatory reviews and post-marketing experience document both benefit and recognized risks (e.g., transient liver enzyme elevations, thrombocytopenia, and immune responses), which are managed with monitoring and prophylactic measures. In short, AAV9's safety profile is well understood and largely favorable when proper precautions are taken. By applying those lessons – choosing safe doses and delivery routes and conducting careful monitoring – we plan to keep our CDKL5 gene therapy both effective and safe for patients.

No, send a note to us through 'Contact Us' page on www.cdkl5genetherapy.com.