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 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]

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 4 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

March 31, 2024

Primary Completion Date

March 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:

          -  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.




3 Months - 60 Months

Accepts Healthy Volunteers



Christopher G Janson, MD, ‪(917) 727-5695‬, [email protected]

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

September 2021