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

Brief Title

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

Official Title

Phase 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

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 [email protected]

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

      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.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Safety evaluation

Secondary Outcome



Canavan Disease



Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 1, 2021

Completion Date

August 31, 2024

Primary Completion Date

August 31, 2023

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.




3 Months - 60 Months

Accepts Healthy Volunteers



Christopher G Janson, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Myrtelle Inc.

Study Sponsor

Christopher G Janson, MD, Principal Investigator, Dayton Children's Hospital

Verification Date

February 2023