#1 Clinical Trials Search in Europe

Adeno-Associated Viral Vector Serotype 9 Expressing Codon-Optimized Human Grn Gene

This article explores the clinical trials of LY3884963, an innovative gene therapy designed to treat Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). The therapy uses an adeno-associated viral vector to deliver a healthy version of the progranulin gene to patients’ cells. The trials aim to assess the safety, tolerability, and effectiveness of this treatment in potentially slowing or halting the progression of this rare form of dementia.

Table of Contents

Introduction

A new potential treatment for a specific type of frontotemporal dementia is currently being studied in clinical trials. This treatment, known as ADENO-ASSOCIATED VIRAL VECTOR SEROTYPE 9 EXPRESSING CODON-OPTIMIZED HUMAN GRN GENE, also referred to as LY3884963 or PR006A, is a type of gene therapy designed to help patients with frontotemporal dementia caused by mutations in the progranulin gene.[1]

What is FTD-GRN?

Frontotemporal Dementia with Progranulin Mutations (FTD-GRN) is a specific type of frontotemporal dementia. Frontotemporal dementia is a group of brain disorders that primarily affect the frontal and temporal lobes of the brain, which are associated with personality, behavior, and language. In FTD-GRN, the disease is caused by mutations in the progranulin gene (GRN), which leads to a deficiency of the progranulin protein in the brain.[1]

How Does the Treatment Work?

LY3884963 is an investigational gene therapy that uses a special type of virus called adeno-associated virus serotype 9 (AAV9) to deliver a healthy copy of the GRN gene to a patient’s brain cells. This gene encodes for the progranulin protein, which is deficient in patients with FTD-GRN. The therapy aims to increase the levels of progranulin in the brain, potentially slowing or halting the progression of the disease.[1]

The treatment is administered through an intracisternal injection, which means it is injected directly into the fluid-filled space at the base of the skull, allowing it to reach the brain more effectively.[1]

Clinical Trial Details

The clinical trial for LY3884963 is called PROCLAIM (A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of LY3884963 in Patients with Fronto-Temporal Dementia with Progranulin Mutations). This study is designed to test different doses of the treatment to determine its safety and effectiveness.[1]

The trial consists of four cohorts:

  1. Low dose: 2.1 × 10^13 viral genomes (vg)
  2. Mid dose: 4.2 × 10^13 vg
  3. High dose (not specified in the provided information)
  4. Bridging cohort: Either low dose or mid dose

Eligibility Criteria

To participate in this clinical trial, patients must meet certain criteria. Some key eligibility requirements include:

  • Age between 30 and 85 years
  • Diagnosed with symptomatic frontotemporal dementia
  • Carrier of a pathogenic progranulin gene (GRN) mutation
  • Generally ambulatory and not dependent on a walker or wheelchair
  • Living in the community (not in a nursing home)
  • Have a reliable study partner/informant

There are also several exclusion criteria, such as having other significant central nervous system diseases or contraindications to the required procedures.[1]

Safety and Efficacy Measures

The study will evaluate several aspects of the treatment’s safety and effectiveness, including:

  • Incidence and severity of side effects
  • Changes in brain and spine MRI scans
  • Changes in progranulin levels in blood and cerebrospinal fluid (CSF)
  • Changes in neurofilament light chain (NfL) levels, a marker of neuronal damage
  • Changes in clinical measures of dementia progression

The study will follow patients for up to 5 years to assess long-term safety and efficacy.[1]

Potential Benefits and Risks

While this treatment shows promise, it’s important to understand that it is still experimental. Potential benefits may include increased progranulin levels and possibly slowed disease progression. However, as with any medical treatment, there are also potential risks.

Some risks may be associated with the injection procedure, the viral vector used, or the immunosuppressant medications given as part of the treatment protocol. The clinical trial is designed to carefully monitor for any adverse effects and to determine the safest and most effective dose.[1]

It’s crucial for patients and their families to discuss the potential benefits and risks with their healthcare providers and the research team before deciding to participate in this or any clinical trial.

Aspect Details
Study Type Phase 1/2 Ascending Dose Study
Condition Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)
Intervention LY3884963 (Adeno-Associated Viral Vector Serotype 9 Expressing Codon-Optimized Human GRN Gene)
Administration Suboccipital injection into the cisterna magna
Primary Objectives Evaluate safety, tolerability, immunogenicity; Quantify PGRN levels in blood and CSF
Secondary Objectives Assess effects on CDR plus NACC FTLD and Neurofilament light chain levels
Dose Cohorts Low dose (2.1 × 10^13 vg), Mid dose (4.2 × 10^13 vg), High dose (not specified)
Study Duration Up to 5 years for safety monitoring
Key Eligibility Criteria Age 30-85, symptomatic FTD, carrier of pathogenic GRN mutation, CDR plus NACC FTLD score ≥0.5 and ≤15

FAQ

  • What is LY3884963 and how does it work? LY3884963 is an investigational gene therapy that uses an adeno-associated viral vector (AAV9) to deliver a healthy version of the progranulin gene (GRN) to a patient's cells. It aims to increase progranulin levels in patients with Frontotemporal Dementia caused by progranulin mutations.
  • Who is eligible for this clinical trial? Eligible participants are men and women aged 30 to 85 years with symptomatic frontotemporal dementia, carrying a pathogenic progranulin gene mutation. They must be generally ambulatory, living in the community, and have a reliable study partner.
  • How is the treatment administered? The treatment is administered via suboccipital injection into the cisterna magna, which is a space at the base of the skull containing cerebrospinal fluid.
  • What are the main objectives of the trial? The main objectives are to evaluate the safety, tolerability, and immunogenicity of LY3884963 at different dose levels, and to measure changes in progranulin levels in blood and cerebrospinal fluid.
  • How long will participants be monitored in the trial? Participants will be monitored for safety endpoints for up to 5 years after receiving the treatment.

Ongoing Clinical Trials on Adeno-Associated Viral Vector Serotype 9 Expressing Codon-Optimized Human Grn Gene

  • Study on the Safety and Effects of LY3884963 for Patients with Fronto-Temporal Dementia with Progranulin Mutations

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium France

Glossary

  • Frontotemporal Dementia (FTD): A group of brain disorders that primarily affect the frontal and temporal lobes of the brain, which are associated with personality, behavior, and language.
  • Progranulin (PGRN): A protein that plays a role in cell growth, wound healing, and inflammation. Mutations in the gene that produces progranulin can lead to frontotemporal dementia.
  • Gene Therapy: A technique that uses genes to treat or prevent disease. In this case, a healthy version of the progranulin gene is delivered to cells to potentially correct the genetic defect.
  • Adeno-Associated Viral Vector (AAV9): A virus that has been modified to deliver genetic material into cells without causing disease. AAV9 is used in this therapy to carry the healthy progranulin gene.
  • Cisterna Magna: A space at the base of the skull filled with cerebrospinal fluid, where the treatment is injected in this study.
  • Cerebrospinal Fluid (CSF): A clear, colorless fluid that surrounds the brain and spinal cord, providing protection and nutrients.
  • Neurofilament Light Chain (NfL): A protein released when neurons are damaged. Its levels in blood and CSF are measured as a potential indicator of treatment effectiveness.
  • Immunogenicity: The ability of a substance to provoke an immune response in the body. In this trial, it's monitored as a safety measure.
  • Clinical Dementia Rating (CDR) plus NACC FTLD: A tool used to assess the severity of dementia symptoms, specifically adapted for frontotemporal lobar degeneration.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-ly3884963-for-patients-with-fronto-temporal-dementia-with-progranulin-mutations/