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

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 [email protected].

Conditions

• Canavan Disease

Interventions

DRUG

rAAV-Olig001-ASPA

Intracerebroventricular administration of a single dose

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.

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.

Sponsors & Collaborators

• Myrtelle Inc.

  lead INDUSTRY

Principal Investigators

• Robert Lober, MD, PhD · Dayton Children's Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Months

Max Age

60 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-04-01

Primary Completion

2026-08-31

Completion

2027-08-31

FDA Drug

Yes

Countries

• United States

Study Locations