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Avb-101

A groundbreaking clinical trial is underway to evaluate AVB-101, a novel gene therapy for patients with Frontotemporal Dementia caused by Progranulin Mutations (FTD-GRN). This Phase 1/2 study aims to assess the safety and potential effectiveness of AVB-101 when administered directly into the brain. The trial offers hope for individuals affected by this rare form of dementia and their families.

Table of Contents

What is AVB-101?

AVB-101, also known as AVB.PGRN, is an innovative medical treatment currently being studied for patients with a specific type of frontotemporal dementia[1]. It is classified as a gene therapy product, which means it uses genetic material to treat a disease[1].

Specifically, AVB-101 is a recombinant AAV-9 vector expressing the human progranulin protein. In simpler terms, it’s a specially designed virus that carries genetic instructions to produce a protein called progranulin in the brain[1].

Target Condition: Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)

AVB-101 is being developed to treat a condition called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)[1]. Let’s break this down:

  • Frontotemporal Dementia (FTD): This is a type of dementia that affects the frontal and temporal lobes of the brain, which are responsible for personality, behavior, and language[1].
  • Progranulin Mutations (GRN): Some people with FTD have mutations in the gene that produces progranulin, a protein important for brain health. These mutations lead to a shortage of progranulin[1].

People with FTD-GRN typically experience changes in personality, behavior, and language skills. The disease is inherited and usually starts affecting people between the ages of 30 and 75[1].

How AVB-101 Works

AVB-101 aims to address the root cause of FTD-GRN by providing the brain with the genetic instructions to produce progranulin[1]. Here’s how it works:

  1. The treatment uses a harmless virus (AAV-9) as a carrier for the healthy progranulin gene.
  2. This virus is injected into specific areas of the brain.
  3. The virus delivers the healthy gene to brain cells.
  4. The brain cells then use this gene to produce the missing progranulin protein.

By increasing progranulin levels in the brain, researchers hope to slow down or potentially stop the progression of FTD-GRN[1].

Administration of AVB-101

AVB-101 is administered through a procedure called bilateral intrathalamic infusion. This means:

  • Bilateral: The treatment is given to both sides of the brain.
  • Intrathalamic: It’s injected into a specific part of the brain called the thalamus.
  • Infusion: The medication is slowly introduced into the brain tissue[1].

This is a surgical procedure that requires general anesthesia and is performed by specialized neurosurgeons[1].

Clinical Trial Details

AVB-101 is currently being studied in a Phase 1/2 clinical trial. Here are some key points about the study:

  • It’s an open-label study, which means both the researchers and participants know which treatment is being given.
  • The study uses ascending doses, meaning they start with a low dose and gradually increase it to find the best balance of effectiveness and safety.
  • The main goal is to evaluate the safety and tolerability of AVB-101.
  • The study also aims to get preliminary data on how well AVB-101 works[1].

Eligibility Criteria

Not everyone with FTD-GRN can participate in this study. Some key eligibility criteria include:

  • Age between 30 and 75 years
  • Confirmed genetic mutation in the progranulin (GRN) gene
  • Diagnosis of frontotemporal dementia
  • Certain scores on cognitive tests
  • Adequate brain structure as seen on MRI scans[1]

There are also several exclusion criteria, such as severe dementia, certain medical conditions, or previous gene therapy treatments[1].

Safety and Efficacy Measures

The study will closely monitor participants for safety and signs that the treatment is working. Some of the key measures include:

  • Adverse events and side effects
  • Changes in cognitive function
  • Brain imaging results
  • Levels of progranulin in the cerebrospinal fluid and blood
  • Levels of neurofilament light chain (NfL), a marker of brain cell damage
  • Changes in clinical dementia rating scales[1]

Participants will be followed for up to 5 years to assess long-term safety and effectiveness[1].

Aspect Details
Study Type Phase 1/2 Open-Label, Ascending Dose, Multicenter Study
Drug Name AVB-101
Target Condition Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)
Administration Method One-time, bilateral intrathalamic infusion
Primary Objectives Evaluate safety and tolerability
Secondary Objectives Assess preliminary clinical efficacy and biomarker changes
Key Eligibility Criteria Age 30-75, confirmed GRN mutation, specific dementia severity scores
Follow-up Period Initial 26 weeks, total 5 years
Key Measurements Safety events, cognitive function, biomarker levels (PGRN, NfL), brain imaging

FAQ

  • What is AVB-101? AVB-101 is a gene therapy designed to treat Frontotemporal Dementia caused by Progranulin Mutations (FTD-GRN). It uses a modified virus to deliver a healthy copy of the progranulin gene to brain cells.
  • How is AVB-101 administered? AVB-101 is administered through a one-time, bilateral intrathalamic infusion. This means it's injected directly into a specific part of the brain called the thalamus on both sides.
  • Who is eligible for this clinical trial? The trial is open to adults aged 30-75 with a confirmed FTD-GRN diagnosis, specific dementia severity scores, and who meet other health criteria. Participants must also have a study partner to support their involvement.
  • What are the main goals of this clinical trial? The primary goals are to evaluate the safety and tolerability of AVB-101 in FTD-GRN patients. Secondary objectives include assessing preliminary clinical effectiveness and measuring changes in biomarkers.
  • How long will participants be monitored after receiving AVB-101? Participants will be monitored for an initial period of 26 weeks, followed by a total follow-up period of 5 years to assess long-term safety and effectiveness.

Ongoing Clinical Trials on Avb-101

  • Study on AVB-101 for Patients with Frontotemporal Dementia with Progranulin Mutations

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Italy The Netherlands Poland Spain Sweden

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 (GRN) Mutation: A genetic change in the GRN gene that leads to reduced production of progranulin protein, which is important for brain cell health and function.
  • Gene Therapy: A technique that uses genes to treat or prevent disease. In this case, it involves delivering a healthy copy of the GRN gene to compensate for the mutated one.
  • Intrathalamic Infusion: A method of delivering medication directly into the thalamus, a part of the brain that acts as a relay center for sensory and motor signals.
  • Biomarker: A measurable indicator of a biological state or condition. In this study, biomarkers are used to assess the effectiveness of the treatment.
  • Clinical Dementia Rating (CDR): A numeric scale used to measure the severity of dementia symptoms.
  • AAV-9 Vector: A type of virus modified for use in gene therapy to deliver genetic material to cells without causing disease.
  • Neurofilament Light Chain (NfL): A protein released when neurons are damaged, used as a biomarker for neurodegeneration.
  • Cerebrospinal Fluid (CSF): Clear fluid surrounding the brain and spinal cord, often used to measure biomarkers of brain health.

References

  1. http://clinicaltrials.eu/trial/study-on-avb-101-for-patients-with-frontotemporal-dementia-with-progranulin-mutations/