Gene Therapy for Neuronal Ceroid Lipofuscinosis

(CLN7 Trial)

Overseen By Souad Messahel, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Benjamin Greenberg

Must not be taking: Antibiotics, Antiepileptics, Chemotherapy, others

Disqualifiers: Neurodegenerative disease, Viral infection, others

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

Compensation: Varies

Number of Visits: 91

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 (AAV9/CLN7) for children with CLN7 Batten disease, a rare and serious condition affecting the nervous system. The study involves a single injection into the lower spine to determine if the treatment is safe and potentially effective in improving movement, thinking, and vision. Children diagnosed with CLN7 who show moderate symptoms, such as speaking in short phrases or walking with assistance, might be suitable candidates for this trial. Participants will not qualify if they have other specific health issues or conditions that could interfere with the study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but new antiepileptic medications should not be started within 90 days of the infusion. It's best to discuss your current medications with the trial team.

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

Research has shown that AAV9/CLN7 gene therapy is safe in animal studies with mice and rats. These studies found it well tolerated, indicating early signs of safety. In humans, this trial is in its early stages and primarily focuses on assessing safety. As a phase 1 trial, the goal is to ensure the treatment does not cause harm and is generally well-tolerated. While this is a promising start, more information from human participants will offer clearer insights into its safety for people. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Batten disease?

Most treatments for Neuronal Ceroid Lipofuscinosis (NCL) focus on managing symptoms rather than addressing the underlying cause. But AAV9/CLN7 works differently, targeting the root of the problem by using gene therapy. This treatment delivers a fully functional MFSD8 gene directly into the patient's cells through a viral vector, potentially providing lifelong benefits. Researchers are excited about its ability to maintain stable gene expression in non-dividing cells, which could significantly improve patient outcomes compared to current options.

What evidence suggests that this gene therapy might be an effective treatment for CLN7 Batten disease?

Research has shown that AAV9/CLN7 gene therapy could be promising for treating CLN7 Batten disease. Early studies demonstrated improvements in animals, especially mice. In lab tests, the therapy restored the waste-processing system in cells from a CLN7 patient. In this trial, participants will receive AAV9/CLN7, which aims to deliver a working gene to the spinal cord area for a long-lasting effect. These early results suggest that AAV9/CLN7 might improve movement, thinking, and intelligence in patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Benjamin Greenberg, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for children aged 1-18 with CLN7 Batten disease, a specific genetic disorder. Participants should have mild to moderate symptoms and be able to perform certain language or motor tasks. They must not require chronic ventilatory support or have other serious health issues that could interfere with the study.

Inclusion Criteria

Platelet count < 100,000/mm3

Any other abnormal lab values that are clinically significant per PI's discretion

Patients selected to be included in this study will have no more than moderate severity of the disease and will have to meet the following criteria; Not dependent on chronic invasive ventilatory support AND have either Expressive language sub test on Mullen and/or Vineland consistent with an age equivalent score of a 2 year 0 month old. This means they should have 20-50 words (all comprehensible) in their vocabulary and putting 2-3 words phrases in a sentence or, Patients can complete and obtain a score of 2-3 on GMFM sub domain E (Walking, Running & jumping) item 67 (ie With 2 hands held can walk 10 steps forward)

Exclusion Criteria

Inability to tolerate anesthesia or study procedures

I started a new epilepsy medication within the last 90 days.

Abnormal lab values that are clinically significant: Platelet count < 100,000/mm3

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intrathecal injection of AAV9/CLN7 gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of motor, cognition, and intelligence

24 months

Multiple visits at Days 90, 180, 360, and 720

What Are the Treatments Tested in This Trial?

Interventions

• AAV9/CLN7

Trial Overview The trial tests a gene therapy called AAV9/CLN7 given as a one-time spinal injection in two different doses. It aims to assess the safety of this treatment and its effectiveness on motor skills, cognition, vision, and brain function in kids with CLN7 disease.

How Is the Trial Designed?

Group I: AAV9/CLN7 Experimental Treatment 1 Intervention

AAV9/CLN7 is an intrathecally administered AAV9-based gene therapy vector that expresses the fully functional form of MFSD8 under the control of a synthetic promoter. AAV9/CLN7 is designed to achieve stable, potentially life-long expression of MFSD8 in non-dividing cells. The first participant will receive a low dose of 5X1014 vg, subsequent participants will receive a higher dose of 1x1015 vg of the AAV9/CLN7 agent.

Who Is Running the Clinical Trial?

Benjamin Greenberg

Lead Sponsor

Trials

1

Recruited

4+

Published Research Related to This Trial

In a mouse model of CLN8 disease, a single neonatal injection of a gene therapy vector (scAAV9) was found to be safe and well tolerated, leading to long-lasting expression of the human CLN8 gene and significant improvements in disease symptoms over a period of 24 months.

This gene therapy not only reduced the disease's behavioral and histopathological effects but also extended the lifespan of treated mice from 10 months to over 24 months, marking a major advancement in potential treatments for CLN8 disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV9 Gene Therapy Increases Lifespan and Treats Pathological and Behavioral Abnormalities in a Mouse Model of CLN8-Batten Disease. Johnson, TB., White, KA., Brudvig, JJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8884894/

CLN7 gene therapy: hope for an ultra-rare condition - PMC Chen et al. present an AAV gene therapy for CLN7 that shows marked benefit in a mouse model of CLN7 Batten disease, paving the way for a phase I trial.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04737460

NCT04737460 | Study for the Treatment for CLN7 Disease The secondary objective is to determine the efficacy of AAV9/CLN7. The secondary outcome measures include motor, cognition and intelligence assessments. The ...

3. jci.org jci.org/articles/view/146286

AAV9/MFSD8 gene therapy is effective in preclinical ... An in vitro study demonstrated that AAV2/MFSD8 dose dependently rescued lysosomal function in fibroblasts from a CLN7 patient.

4. withpower.com withpower.com/trial/phase-1-4-2021-f7ca6

Gene Therapy for Neuronal Ceroid Lipofuscinosis In preclinical studies, AAV9/CLN7 gene therapy was found to be safe and well tolerated in animal models, including mice and rats. While human trials are still ...

5. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT04737460

Study for the Treatment for CLN7 Disease The exploratory outcome measures include visual impairment assessment, cognitive evaluations, Brain magnetic resonance imaging (MRI), electroencephalogram (EEG) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8884910/

AAV9/MFSD8 gene therapy is effective in preclinical models of ... An in vitro study demonstrated that AAV2/MFSD8 dose dependently rescued lysosomal function in fibroblasts from a CLN7 patient.