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

NCT ID: NCT04833907

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2027-08-31

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.

Detailed Description

rAAV-Olig001-ASPA is the first gene therapy designed to target the oligodendrocytes, which are critical for myelination and brain development.

This study is a Phase 1/2 First-In-Human protocol designed to obtain safety, pharmacodynamics, and efficacy data following neurosurgical administration of a single dose of rAAV-Olig001-ASPA delivered intracerebroventricularly in up to 24 children with Canavan Disease.

Patients with a diagnosis of typical Canavan Disease who meet all eligibility criteria may be enrolled in this open-label, sequential cohort study of a single dose of rAAV-Olig001-ASPA.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

rAAV-Olig001-ASPA

Intervention Type: DRUG

Intracerebroventricular administration of a single dose

Levetiracetam

Intervention Type: 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.

Prednisone

Intervention Type: 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.

Interventions

rAAV-Olig001-ASPA

Intracerebroventricular administration of a single dose

Intervention Type: DRUG

Levetiracetam

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.

Intervention Type: DRUG

Prednisone

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.

Intervention Type: DRUG

Other Intervention Names

MYR-101; Keppra

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 60 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Myrtelle Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Lober, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dayton Children's Hospital

Locations

Dayton Children's Hospital

Dayton, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 33614826 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27717881 (View on PubMed)

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 Sep 16. doi: 10.1038/s41591-025-03919-w. Online ahead of print.

Reference Type: DERIVED

PMID: 40957959 (View on PubMed)

Related Links

https://rarediseases.info.nih.gov/diseases/5984/canavan-disease

Canavan Disease

https://research.rowan.edu/research-areas/biomedical/leone/index.html

Canavan Disease Research

https://curecanavanfund.org

Canavan Disease Advocacy, Research, Patient assistance, Education

http://www.canavan.org

Canavan Disease Advocacy, Research, Patient assistance, Education

https://www.canavanfoundation.org

Canavan Disease Advocacy, Research, Patient assistance, Education

https://www.canavanresearch.org

Canavan Disease Advocacy, Research, Patient assistance, Education

https://www.ntsad.org

Canavan Disease Advocacy, Research, Patient assistance, Education

Other Identifiers

CAN-GT

Identifier Type: -

Identifier Source: org_study_id