Gene Therapy for Canavan Disease

(CAN-GT Trial)

Overseen By Jordana Holovach

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Myrtelle LLC

Disqualifiers: Chronic medical conditions, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment for Canavan Disease, a severe genetic disorder affecting brain function and development. The treatment, rAAV-Olig001-ASPA gene therapy, uses a viral vector to deliver a healthy gene directly to the brain cells impacted by the disease, addressing the core issues. It is designed for children diagnosed with Canavan Disease by a neurologist. The trial aims to determine if this approach can improve symptoms and offer a safer, more effective treatment option for those with this challenging condition. As a Phase 1/Phase 2 trial, it focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, providing a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this gene therapy is likely to be safe for humans?

Research has shown that the gene therapy rAAV-Olig001-ASPA has been generally well tolerated in earlier studies. Eight people received this treatment, and it proved safe for most, as they did not experience serious side effects. Participants in these trials demonstrated improvement in brain myelin volume, which is encouraging. This therapy uses a virus to deliver the gene and is administered directly to the brain through surgery. Although this might sound complex, the therapy has shown promising results without major safety concerns so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Canavan Disease, which primarily focuses on supportive management and symptom relief, rAAV-Olig001-ASPA introduces a groundbreaking gene therapy approach. This treatment is unique because it uses a recombinant adeno-associated virus (rAAV) to deliver the ASPA gene directly into the brain via neurosurgical administration. This method targets the root cause of the disease by aiming to correct the underlying genetic defect, offering potential for more effective long-term outcomes. Researchers are excited about this therapy because it has the potential to significantly alter the disease's progression, which current treatments cannot achieve.

What evidence suggests that this gene therapy could be effective for Canavan Disease?

Research has shown that the gene therapy rAAV-Olig001-ASPA, which participants in this trial will receive, holds promise for treating Canavan Disease. Studies have found that this therapy reduces levels of N-acetylaspartate (NAA) in the brain. Lowering NAA is crucial because high levels are linked to the severe symptoms of Canavan Disease. The therapy also increases myelin in the brain, essential for proper brain function and development. It targets specific brain cells called oligodendrocytes, responsible for making myelin, and aims to restore their function. These findings suggest that rAAV-Olig001-ASPA could potentially improve the condition in patients with Canavan Disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Robert Lober, MD, PhD

Principal Investigator

Dayton Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children with typical Canavan Disease, a brain disorder. Eligible participants are aged 3-60 months and diagnosed by a neurologist. They can't have had gene therapy or intracranial surgery before, severe allergies, MRI contraindications, immune system issues, or other serious health problems.

Inclusion Criteria

You have been diagnosed with typical CD by a neurologist who is certified by the board.

Written informed consent from parent(s)/guardian(s) including a written agreement to comply with all the conditions of the study

My child is younger than 15 months.

Exclusion Criteria

You are expected to live for less than 12 months for any reason.

Your lab test results are not within the normal range and the doctor in charge decides they are important.

Your GMFM-88 score is higher than 35%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Neurosurgical administration of a single dose of rAAV-Olig001-ASPA delivered intracerebroventricularly

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurological evaluations and imaging

12 months

Multiple visits (in-person and virtual)

Long-term follow-up

Extended monitoring of participants for long-term safety and efficacy outcomes

Additional 12 months

What Are the Treatments Tested in This Trial?

Interventions

• rAAV-Olig001-ASPA

Trial Overview The trial tests rAAV-Olig001-ASPA gene therapy delivered directly to the brain to treat Canavan Disease. It aims to restore enzyme function in cells responsible for producing white matter. The study includes clinical assessments and brain imaging over time.

How Is the Trial Designed?

Group I: 3.7 x 10^13 v.g. rAAV-Olig001-ASPA Experimental Treatment 3 Interventions

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

rAAV-Olig001-ASPA is already approved in United States, European Union for the following indications:

Approved in United States as rAAV-Olig001-ASPA Gene Therapy for:

• Orphan Drug, Fast-Track and Rare Pediatric Disease Designations for the treatment of Canavan disease

Approved in European Union as rAAV-Olig001-ASPA Gene Therapy for:

• Orphan Drug Designation for the treatment of Canavan disease

Who Is Running the Clinical Trial?

Myrtelle LLC

Lead Sponsor

Trials

1

Recruited

20+

Myrtelle Inc.

Lead Sponsor

Trials

2

Recruited

12,000+

Published Research Related to This Trial

The novel AAV capsid variant AAV/Olig001 demonstrated over 70% oligotropism in key brain regions for Canavan disease treatment, effectively targeting oligodendrocytes without needing specific expression elements.

Using intracerebroventricular infusion to deliver AAV/Olig001 led to a dose-dependent improvement in enzyme activity and motor function in Canavan mice, showing significant advantages over the AAV9 vector, which supports its potential for clinical use in white matter diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease. Francis, JS., Markov, V., Wojtas, ID., et al.[2021]

In a study of 28 patients with Canavan disease, gene therapy using the AAV2-ASPA vector showed long-term safety with no significant adverse events over a minimum 5-year follow-up period.

The treatment led to a decrease in elevated N-acetyl-aspartate (NAA) levels in the brain, slowed brain atrophy progression, and showed some improvement in seizure frequency and overall clinical stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up after gene therapy for canavan disease. Leone, P., Shera, D., McPhee, SW., et al.[2022]

The non-viral lipid-entrapped delivery system (LPD) for gene therapy demonstrated effective and safe gene transfer in both animal models and preliminary studies in 2 children with Canavan disease, showing no significant adverse effects.

In animal studies, the gene delivery system resulted in widespread gene expression for over 10 months, and in the children, it was associated with positive biochemical and clinical changes, indicating potential efficacy for treating neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Leone, P., Janson, CG., Bilaniuk, L., et al.[2019]

The study involved ten subjects receiving a gene therapy for Canavan disease using a viral vector (rAAV2) delivered directly to the brain, which showed promising safety with minimal immune response and inflammation.

Most subjects (7 out of 10) did not develop neutralizing antibodies against the AAV2 vector, indicating that the treatment is well tolerated and suggesting a relatively safe profile for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune responses to AAV in a phase I study for Canavan disease. McPhee, SW., Janson, CG., Li, C., et al.[2012]

This clinical protocol outlines a groundbreaking approach using virus-based gene transfer to treat Canavan disease, a severe childhood disorder caused by a defective gene for the enzyme aspartoacylase, affecting brain myelination.

The study involves administering approximately 900 billion genomic particles of a recombinant adeno-associated virus (AAV) containing the functional ASPA gene directly into the brains of 21 patients, marking the first use of AAV for gene therapy in humans and potentially offering a new treatment avenue for neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Janson, C., McPhee, S., Bilaniuk, L., et al.[2012]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04833907

Study Details | NCT04833907 | rAAV-Olig001-ASPA Gene ... 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 ...

2. prnewswire.com prnewswire.com/news-releases/myrtelle-announces-nature-medicine-publication-of-interim-results-from-its-phase-12-clinical-trial-of-investigational-gene-therapy-raav-olig001-aspa-for-canavan-disease-302557585.html

Myrtelle Announces Nature Medicine Publication of Interim ... Groundbreaking study demonstrates that targeted oligodendrocyte gene therapy leads to decreased N-acetylaspartate (NAA) levels and increased ...

3. canavanfoundation.org canavanfoundation.org/updates

News & Updates Groundbreaking study demonstrates that targeted oligodendrocyte gene therapy leads to decreased N-acetylaspartate (NAA) levels and increased brain myelin volume ...

4. firstwordpharma.com firstwordpharma.com/story/6314360

Myrtelle Announces Presentation of Encouraging Interim ... Myrtelle Announces Presentation of Encouraging Interim Results from its Phase 1/2 Gene Therapy Trial for Canavan Disease at the 2025 Cell & Gene ...

5. alextlc.org alextlc.org/research/myrtelle-positive-data-raav-olig001-aspa-gene-therapy-in-canavan-disease/

Myrtelle Announces Positive Data for Its investigational ... This article highlights the possible usage of rAAV-Olig001-ASPA Gene Therapy created by Myrtelle for treating Canavan Disease (CD). Specifically, CD is an ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40957959/

Oligodendrocyte-targeted adeno-associated virus gene ... A total of 8 participants received intracranial doses of 3.7 × 1013 vector genomes (vg) of rAAV-Olig001-ASPA (MYR-101), with an interim analysis ...

7. cgtlive.com cgtlive.com/view/myrtelle-canavan-disease-gene-therapy-effects-significant-decrease-csf-naa-increases-brain-myelin-volume

Myrtelle's Canavan Disease Gene Therapy Effects ... With regard to safety, MYR-101 was characterized as “well tolerated” with a “favorable safety profile.”