rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

NCT04833907 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: CAN-GT
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Canavan Disease is a congenital white matter disorder caused by mutations to the gene encoding for aspartoacylase (ASPA). Expression of ASPA is restricted to oligodendrocytes, the sole white matter producing lineage in the brain. ASPA supports myelination in the capacity of its sole known function, namely, the catabolism of N-acetylaspartate (NAA). Inherited mutations that result in loss of ASPA catabolic activity result in a typically severe phenotype of Canavan Disease, characterized by chronically elevated brain NAA, gross motor abnormalities, hypomyelination, progressive spongiform degeneration of the brain, epilepsy, blindness, and a short life expectancy. Disease severity is correlated with residual levels of enzyme activity. Reconstitution of ASPA function in oligodendrocytes of the brains of Canavan patients is expected to rescue NAA metabolism in its natural cellular compartment and support myelination/remyelination by resident white matter producing cells. This protocol directly targets oligodendrocytes in the brain, which are intimately involved with disease initiation and progression. Targeting oligodendrocytes offers the safest and most direct therapy for affected individuals. The latest generation AAV viral vector (rAAV-Olig001-ASPA) will be administered to patients using neurosurgical procedure which involves direct administration of gene therapy to affected regions of the brain. Outcome measures for the open label clinical trial include longitudinal clinical assessments and brain imaging. Currently, there is no effective treatment for Canavan Disease. The purpose of this study is to validate a new technology targeted to the cells most affected by Canavan Disease in the safest way possible. The study investigators are committed to supporting the Rare Disease \& Canavan Disease Communities. For more information, please contact Jordana Holovach, Head of Communications and Community at PatientAdvocacy@myrtellegtx.com.

Conditions

Canavan Disease

Keywords

Canavan Disease; Gene Therapy; Aspartoacylase; N-Acetyl-Aspartate; Oligodendrocyte; Leukodystrophy; Adeno-Associated Virus Vector; Autosomal Recessive Disorder; Neurodegenerative; White Matter Disorder

Outcome Measures

Primary Outcomes (1)

• Safety evaluation

  Number, severity, and causal relationship of any adverse event (to either the gene therapy and/or surgical trial procedures required for vector administration) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  12 Months Post Dose

Secondary Outcomes (7)

• Myelination

  12 Months Post Dose

• N-Acetyl-Aspartate (NAA) concentrations in the Brain

  12 Months Post Dose

• Neurological Evaluation - Motor Function

  12 Months Post Dose

• Neurological Evaluation - Neurocognitive Function

  12 Months Post Dose

• Neurological Evaluation - Spasticity

  12 Months Post Dose

Study Arms (1)

3.7 x 10^13 v.g. rAAV-Olig001-ASPA

EXPERIMENTAL

3.7 x 10\^13 v.g. of rAAV-Olig001-ASPA administered as a single dose neurosurgically to the brain via 2 pre-defined intracerebroventricular sites

Drug: rAAV-Olig001-ASPA; Drug: Levetiracetam; Drug: Prednisone

Interventions

rAAV-Olig001-ASPA DRUG

Intracerebroventricular administration of a single dose

Also known as: MYR-101

3.7 x 10^13 v.g. rAAV-Olig001-ASPA

Levetiracetam DRUG

Keppra daily dose (20-50 mg/kg/day divided twice daily administered orally or per G-tube) in the post-operative period and continued for 3 months per standard of care to prevent seizure activity.

Also known as: Keppra

3.7 x 10^13 v.g. rAAV-Olig001-ASPA

Prednisone DRUG

Post-operatively, a 3-month steroid taper is planned to prevent or reduce possible delayed immunological responses. This tapering regimen will consist of 0.5 mg/kg/day prednisone during weeks 1-4; followed by 0.3 mg/kg/day prednisone during weeks 5-8; and 0.1mg prednisone during weeks 9-12, then off. If there is evidence of new inflammation on MRI at 3-months on T2 FLAIR, the steroid taper will be extended for an additional 3 months or we will transition to steroid-sparing immunosuppression.

3.7 x 10^13 v.g. rAAV-Olig001-ASPA

Eligibility Criteria

• Age: 3 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Definitive diagnosis of typical CD by a board certified neurologist.
• Written informed consent from parent(s)/guardian(s). Consent to enroll into the study will include a written agreement to comply with all the conditions of the study, including attendance at follow-up visits.
• For cohort 1: age more than 36 months and up to 60 months.
• For cohort 2: age between 15 months and 36 months.
• For cohort 3: age less than 15 months.

You may not qualify if:

• At the discretion of the PI, any significant chronic medical condition, including, but not limited to neurological, cardiac, hepatic, renal, hematological, gastrointestinal, endocrine, pulmonary, or infectious disease, which would put the subject at increased risk during surgery or which would interfere with participation in the study, interpretation of safety monitoring, or the integrity of the study data.
• History of severe allergic reaction or anaphylaxis.
• Past participation in gene therapy trials or receipt of any other investigational product within 6 months prior to enrollment.
• Prior intracranial surgery.
• Any absolute contraindication to immunosuppression.
• Any absolute contraindication to MRI.
• Any vaccination less than 1 month prior to gene therapy.
• Anticipated life expectancy of less than 12 months for any reason.
• GMFM-88 total raw score \>35%.
• Clinically significant out-of-range lab values, at the discretion of clinical PI.

Sponsors & Collaborators

• Myrtelle Inc.: lead

Study Sites (1)

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Related Publications (3)

• Francis JS, Markov V, Wojtas ID, Gray S, McCown T, Samulski RJ, Figueroa M, Leone P. Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease. Mol Ther Methods Clin Dev. 2021 Jan 21;20:520-534. doi: 10.1016/j.omtm.2021.01.009. eCollection 2021 Mar 12.

  PMID: 33614826 BACKGROUND

• Francis JS, Wojtas I, Markov V, Gray SJ, McCown TJ, Samulski RJ, Bilaniuk LT, Wang DJ, De Vivo DC, Janson CG, Leone P. N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase. Neurobiol Dis. 2016 Dec;96:323-334. doi: 10.1016/j.nbd.2016.10.001. Epub 2016 Oct 4.

  PMID: 27717881 BACKGROUND

• Leone P, Lober RM, Francis J, Flamini O, Cecil KM, Shera D, Janson CG. Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial. Nat Med. 2025 Nov;31(11):3772-3779. doi: 10.1038/s41591-025-03919-w. Epub 2025 Sep 16.

  PMID: 40957959 DERIVED

Related Links

• Canavan Disease
• Canavan Disease Research
• Canavan Disease Advocacy, Research, Patient assistance, Education
• Canavan Disease Advocacy, Research, Patient assistance, Education
• Canavan Disease Advocacy, Research, Patient assistance, Education
• Canavan Disease Advocacy, Research, Patient assistance, Education
• Canavan Disease Advocacy, Research, Patient assistance, Education

MeSH Terms

Conditions

Canavan Disease

Interventions

Levetiracetam; Prednisone

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Robert Lober, MD, PhD

  Dayton Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 6, 2021
• Study Start: April 1, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)