An observational study in Hypoxic Brain Damage, Hypoxic Ischaemic Encephalopathy (HIE) and Hypoxic Ischaemic Encephalopathy Due to Cardiac Arrest, sponsored by Healing Hope International. Enrolling by invitation at 1 site in Mexico. Open to participants aged 2 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-03-23.
Sponsored by Healing Hope International · Observational
This international study, organized by Healing Hope International, is an observational registry designed to collect real-world data on participants living with chronic hypoxic ischemic encephalopathy (HIE) who receive an emerging intranasal gene therapy based on the AAV9-PHP.eB viral vector.
The investigational therapy delivers a panel of 15 restorative genes that support brain repair, reduce inflammation, promote myelination, and improve neural communication. It is administered intranasally in one or three sessions by participating international clinical teams. Because the therapy is already being offered abroad, this registry does not assign treatment but instead follows participants who have received it as part of their existing medical care.
The GEN HOPE Study aims to understand how this gene therapy affects movement, cognition, spasticity, and seizure frequency over time. Families and clinicians will share outcomes such as changes in gross motor function (GMFM-66/88), cognitive assessments (Bayley or WISC tests), and quality-of-life measures. Information on safety, laboratory results, MRI findings, and caregiver-reported experiences will also be collected.
By combining data from multiple countries, the registry seeks to evaluate whether this novel gene based approach can meaningfully improve daily function and comfort for participants with chronic HIE. Results will guide future clinical trial development and help define safe and effective standards of care for regenerative neurologic therapies.
The GEN HOPE Study is a multinational, real world observational registry coordinated by Healing Hope International to characterize reported safety events and functional outcomes in participants with chronic hypoxic ischemic encephalopathy (HIE), a condition commonly presenting as cerebral palsy, who have received intranasal 15-gene AAV9-PHP.eB gene therapy outside the United States.
This registry does not assign or direct any medical intervention. Instead, it prospectively collects standardized clinical and caregiver reported data from participating international sites where the therapy is already being used under local medical supervision. The aim is to document the naturalistic course of recovery following treatment and to generate evidence that may inform the design of future controlled trials.
The investigational therapy uses an AAV9-PHP.eB viral vector optimized for central nervous system delivery through the nasal mucosa. The 15 gene panel encodes factors related to neuronal plasticity, white matter repair, antiinflammatory modulation, metabolic and vascular support, and cellular longevity. Dosing schedules vary by site (single session or three session delivery), and some centers administer short-term rapamycin as an adjunctive immunomodulator.
Participants aged 2-65 years who have documented chronic HIE, stable baseline medical status, and caregiver consent to share outcome data. Key assessments include gross motor function (GMFM-66/88), cognitive and language evaluations (Bayley-III/IV or WISC-V), spasticity and seizure frequency, and quality-of-life and caregiver burden metrics. Whenever available, MRI/DTI data and laboratory monitoring are recorded. Follow-up intervals occur at approximately 3, 6, 12, 18, and 24 months post-treatment.
Data are analyzed using target-trial emulation and propensity-weighted methods to estimate treatment effects compared with matched external controls receiving standard care. The primary outcome is change in GMFM-66/88 score at 12 months. Secondary outcomes include cognitive performance, seizure burden, quality of life, and safety parameters.
All information is deidentified and stored in a secure international database compliant with data protection and ethical governance standards. Oversight is provided by an independent Data and Safety Monitoring Board (DSMB) with expertise in neurology, statistics, and gene-therapy safety.
The GEN HOPE Study seeks to accelerate understanding of gene based neurorestorative strategies and to establish a transparent evidence base supporting compassionate use access, long-term safety monitoring, and eventual clinical trial harmonization for participants affected by HIE worldwide.
The study population consists of patients aged 2 to 60 years with chronic hypoxic-ischemic encephalopathy (HIE) who have undergone or are undergoing intranasal 15-gene AAV9-PHP.eB gene therapy at participating international clinical sites.
Participants typically present with moderate to severe motor and cognitive impairments resulting from neonatal brain injury. Most rely on rehabilitative therapies such as occupational, physical, or speech therapy, and many have comorbid spasticity, seizure disorders, or feeding and respiratory challenges.
Families voluntarily enroll to share functional, cognitive, imaging, and quality-of-life outcomes following the therapy, allowing the registry to capture real-world data from diverse treatment centers. Enrollment is open to patients meeting medical stability criteria and caregiver consent requirements, regardless of geographic origin, socioeconomic background, or previous therapy history.
No healthy volunteers are included.
Exclusion Criteria:
This cohort includes patients diagnosed with chronic hypoxic-ischemic encephalopathy (HIE) who receive an intranasal 15-gene AAV9-PHP.eB therapy as part of their existing medical care at participating international sites.
Change in Gross Motor Function Measure (GMFM-66/88) Score From Baseline to 12 Months
Assesses change in overall motor ability using the Gross Motor Function Measure (GMFM-66/88), a validated scale for patients with cerebral palsy and/or hypoxic ischemic injury. Measures performance in lying, sitting, crawling, standing, and walking domains. Higher scores indicate greater motor function.
Time frame: Baseline to 12 months after treatment
Change in Cognitive Performance (Bayley Scales) From Baseline
Assesses change in cognitive performance using the Bayley Scales of Infant and Toddler Development (Bayley-III or Bayley-IV) for participants aged 2-4 years. Composite cognitive scores range from 40-160 (mean 100, SD 15), with higher scores indicating improved cognitive and developmental function.
Time frame: Baseline to 12 months and 24 months
Change in Seizure Frequency
Monthly caregiver-reported seizure logs and medication records are collected to quantify changes in seizure frequency. Reduction in seizure rate indicates improvement in neuronal stability and anti-inflammatory response. Seizure frequency is a count measure-no minimum/maximum scale required.
Time frame: Baseline to 12 months and 24 months
Change in Spasticity Using the Modified Ashworth Scale (MAS)
Measures tone and resistance in major muscle groups using the Modified Ashworth Scale (0 = no increase in tone; 4 = rigid in flexion or extension). Lower scores indicate reduced spasticity.
Time frame: Baseline to 12 months
Change in Quality of Life (PedsQL Caregiver-Reported Score)
Assesses child and caregiver quality of life using the Pediatric Quality of Life Inventory (PedsQL). Scale range: 0-100, with higher scores indicating improved perceived quality of life.
Time frame: Baseline to 12 months and 24 months
Change in MRI/DTI Biomarkers of White-Matter Integrity
Quantitative analysis of fractional anisotropy and mean diffusivity from diffusion tensor imaging (DTI) in periventricular and cortical regions. Increases in fractional anisotropy and cortical thickness suggest structural neurorepair.
Time frame: Baseline to 12 months
Change in Cognitive Performance (WISC-V) From Baseline
Assesses change in cognitive performance using the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V) for participants aged 5-10 years. Full Scale IQ scores range from 40-160, with higher scores indicating improved cognitive function.
Time frame: Baseline to 12 months and 24 months
Change in Caregiver Burden Score
Measured using the Caregiver Strain Index (CSI). Lower scores indicate reduced physical, emotional, and time-related burden associated with caregiving.
Time frame: Baseline to 12 months and 24 months
Incidence of Adverse Events and Serious Adverse Events
Safety endpoints include frequency and severity of adverse events, infections, seizure exacerbations, or hospitalization following gene therapy administration.
Time frame: Treatment through 24-month follow-up
Change in Functional Communication (PEDI-CAT / CP-CHILD)
Evaluates communication and social interaction using validated scales (PEDI-CAT Communication Domain and CP-CHILD). Higher scores indicate improved communication function.
Time frame: Baseline to 12 months
Change in Laboratory Safety Parameters During Rapamycin Use
Assesses the number of participants who develop laboratory abnormalities while receiving adjunctive rapamycin. Monitored parameters include complete blood count (CBC), liver enzymes (AST, ALT), renal function markers (creatinine, BUN), and lipid profile (LDL, HDL, triglycerides). Abnormalities are defined according to site-specific laboratory reference ranges. The outcome is reported as the number of participants exhibiting at least one laboratory value outside the normal range.
Time frame: Baseline, Weeks 2, 4, 8, and 12
Change in Anti-AAV9-PHP.eB Antibody Titers
Quantifies humoral immune response to AAV9-PHP.eB using ELISA or equivalent assays where available.
Time frame: Baseline to 6 months post-treatment
Plan to share: Undecided — Individual participant data will not be publicly shared because the registry collects information from medically fragile children with hypoxic-ischemic encephalopathy across international sites. The data contain potentially identifiable clinical and imaging information that cannot be fully anonymized without risk of re-identification. De-identified, aggregate-level results and statistical summaries will be made available through peer-reviewed publications, conference presentations, and registry updates. Access to limited, de-identified datasets for qualified researchers may be considered under controlled data-use agreements and ethics committee approval.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Healing Hope International