Giant axonal neuropathy (GAN) is a rare pediatric disorder caused by autosomal recessive mutations in the GAN gene. GAN is a multisystem, neurodegenerative disorder affecting the peripheral nervous system (PNS), central nervous system (CNS) and autonomic nervous system (ANS).
GAN is a fatal disease with many patients not surviving past early adulthood due to aspiration pneumonia and pulmonary com…
Giant axonal neuropathy (GAN) is a rare pediatric disorder caused by autosomal recessive mutations in the GAN gene. GAN is a multisystem, neurodegenerative disorder affecting the peripheral nervous system (PNS), central nervous system (CNS) and autonomic nervous system (ANS).
GAN is a fatal disease with many patients not surviving past early adulthood due to aspiration pneumonia and pulmonary complications. Currently, there are no approved drugs or other therapies for the treatment of GAN; and only supportive care therapies exist, leaving an unmet medical need to treat this rare, progressive, and ultimately fatal neurodegenerative disease.
The drug used in this study (scAAV9/JeT-GAN) has been studied in a previous gene therapy clinical trial by which the drug was administered as a single injection into the spinal canal (intrathecal \[IT\] administration) to treat the symptoms associated with the CNS and PNS neurodegeneration; however, this administration method did not address the symptoms associated with neurodegeneration of the ANS.
To treat the symptoms associated with ANS, this study has been designed to evaluate the safety and tolerability of a single dose of scAAV9/JeT-GAN administered directly into the left vagus nerve (intraneurally) in participants who have previously received scAAV9/JeT-GAN administered intrathecally.
This study involves the use of an investigational drug called scAAV9/JeT-GAN "Investigational" means that the drug has not been approved by the U.S. Food \& Drug Administration (FDA) for the treatment of GAN and the progression of neurodegeneration to the CNS, PNS and ANS.
This is the first study in humans to administer the drug directly into the left vagus nerve. We want to find out what effects, good and/or bad, scAAV9/JeT-GAN has when administered directly into the vagus nerve.
The safety of intrathecal (IT) administration of scAAV9/JeT-GAN has been established in a prior research study; however, the people in this study will be the first people to receive the drug intraneurally. As a result, information about the safety and effectiveness of the route of administration is incomplete and all of the possible side effects are not yet known.
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Eligibility Criteria
Inclusion Criteria:
1. Confirmed diagnosis of GAN disease by:
1. Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or confirmed pathogenic variants in the GAN gene;
2. Clinical history or symptoms to ANS dysfunction.
2. Previously treated with IT…
Inclusion Criteria:
1. Confirmed diagnosis of GAN disease by:
1. Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, pathogenic and/or confirmed pathogenic variants in the GAN gene;
2. Clinical history or symptoms to ANS dysfunction.
2. Previously treated with IT AAV/GAN and completion of 5 year follow up prior to enrollment.
3. Parents/l LAR willing to accompany the participant to all study visits and who will provide consent for their child's participation.
4. Subject able to comply with all protocol requirements and procedures.
5. Up to date on childhood vaccinations according to Centers for Disease Control (CDC) guidelines. Annual influenza and COVID-19 vaccinations are highly recommended.
6. Female participants of child-bearing potential must have a negative urine and/or negative serum pregnancy test at screening/baseline; (a) Female participants must agree to use an effective form of birth control during study participation.
Exclusion Criteria:
1. Inability to participate in study procedures (as determined by the site investigator).
2. Inability to be safely sedated in the opinion of the clinical anesthesiologist.
3. Concomitant illness or requirement for chronic drug treatment that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer.
4. The presence of significant non-GAN related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
5. Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than this gene therapy) during the study.
6. Currently participating in another interventional (drug/device) clinical trial.
7. Experienced an SAE (serious adverse event) related to scAAV9/JeT-GAN while participating in the first GAN IT study.
8. Contraindication to scAAV9/JeT-GAN or any of its ingredients.
9. Contraindication to any of the immune suppression medications used in this study.
10. Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy
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