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

• Status: Recruiting
• Trial end date: 2024-03-31
• Target enrollment: 0
• Participant gender: All

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 developmental 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 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 a minimally invasive 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].

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CureRareDisease LLC; Myrtelle Inc.
• Treatments: Levetiracetam; Prednisolone; Prednisolone phosphate

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:

• Any significant chronic medical condition other than CD or its complications, 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 interpretation of safety monitoring, at the discretion of clinical Principal Investigator (PI).

• 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 >15%.

• Clinically significant out-of-range lab values, at the discretion of clinical PI.