What side effects are associated with this type of intervention?

Common treatments for Frontotemporal Dementia (FTD) include medications that target symptoms such as behavioral changes, cognitive decline, and motor symptoms. These treatments often involve antidepressants, antipsychotics, and cognitive enhancers. Known side effects of these medications can include nausea, weight gain, sedation, and increased risk of metabolic syndrome. For treatments similar to LY3884963, which modulates progranulin protein levels, potential side effects may include immune reactions, injection site reactions, and changes in biomarker levels. As LY3884963 is still under investigation, its specific side effect profile is not fully established.

What prior FDA approvals exist?

Currently, there are no specific FDA-approved treatments for Frontotemporal Dementia (FTD) that focus on the modulation of progranulin protein levels. The trial of LY3884963 is an investigational approach targeting this mechanism. Broadly, treatment for FTD is symptomatic, focusing on managing behavioral symptoms and cognitive decline, often using medications approved for other types of dementia or psychiatric conditions.

What other types of research exist?

Promising novel alternatives to LY3884963 for Frontotemporal Dementia (FTD) patients include: 1) Antisense oligonucleotide therapies targeting specific genetic mutations associated with FTD, such as those in the C9orf72 gene. 2) Gene editing technologies like CRISPR-Cas9 aimed at correcting genetic defects. 3) Small molecule inhibitors that modulate protein aggregation and misfolding, such as those targeting TDP-43 or tau proteins. 4) Immunotherapies designed to clear pathological protein aggregates. These approaches are in various stages of research and development and may offer new avenues for treatment in the near future.

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Virus Therapy

PR006 for Frontotemporal Dementia (PROCLAIM Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Prevail Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient and/or patient's legally authorized representative has the ability to understand the purpose and risks of the study, and provide written informed consent and authorization to use protected health information.

Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lb) and a BMI of 18 to 34 kg/m2.

Must not have

Diagnosis of a significant CNS (central nervous system) disease other than frontotemporal dementia (FTD) that may cause FTD symptoms or confound study objectives.

Hypersensitivity or contraindications to corticosteroid, and/or sirolimus use.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called LY3884963 to help people with a specific type of dementia. The drug is given directly to the brain to increase a protein that could improve their condition. The study focuses on patients with genetic mutations that affect their response to usual treatments.

Who is the study for?

This trial is for adults aged 30-85 with frontotemporal dementia due to progranulin gene mutations. Participants must be living in the community, not dependent on a walker or wheelchair, have up-to-date vaccinations and cancer screenings, and test negative for tuberculosis. They need a reliable informant to report on their health status.

What is being tested?

The study tests LY3884963's safety and its effect on protein levels related to dementia when administered into the spinal fluid. Optional treatments include Sirolimus and Prednisone. Over five years, patients will be monitored through various doses of LY3884963 for changes in biomarkers and clinical outcomes.

What are the potential side effects?

Potential side effects may include reactions at the injection site, immune system responses due to drug components like corticosteroids or sirolimus, as well as general risks associated with anesthesia required during administration.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I understand the study's risks and can give my consent.

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My weight is between 88 and 242 lbs, and my BMI is between 18 and 34.

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I do not rely on a walker or wheelchair to move around.

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I have been diagnosed with frontotemporal dementia and have symptoms.

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I carry a mutation in the progranulin gene.

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I am between 30 and 85 years old.

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I carry a mutation in the GRN gene.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a brain condition that is not frontotemporal dementia but could cause similar symptoms.

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I am allergic or cannot take corticosteroid or sirolimus.

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I cannot undergo general anesthesia or deep sedation due to health risks.

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I have not had any gene or cell therapy before.

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My brain or spine MRI shows I can't have an ICM injection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in AAV9 immunogenicity in blood

Change in AAV9, PGRN, and NfL immunogenicity in CSF

Change in PGRN immunogenicity in CSF

+2 more

Secondary study objectives

Change in CDR plus NACC FTLD

Change in NfL levels in blood

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Initial Cohort - Medium doseExperimental Treatment4 Interventions

Group II: Initial Cohort - Low doseExperimental Treatment4 Interventions

Group III: Bridging Cohort - Medium doseExperimental Treatment4 Interventions

Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner

Group IV: Bridging Cohort - Low doseExperimental Treatment4 Interventions

Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Methylprednisolone

2015

Completed Phase 4

~2280

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Frontotemporal Dementia (FTD) include medications that target neurotransmitter imbalances and experimental therapies aimed at disease-modifying mechanisms. One such experimental approach involves modulating progranulin protein levels, as seen in the trial LY3884963. Progranulin is a protein that plays a crucial role in neuronal survival and inflammation regulation. In FTD patients with progranulin mutations, there is often a deficiency of this protein, leading to neurodegeneration. By increasing progranulin levels, treatments like LY3884963 aim to slow disease progression and improve neuronal function. This is particularly important for FTD patients as it addresses the underlying pathology rather than just alleviating symptoms.

Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice.Elevated TMEM106B levels exaggerate lipofuscin accumulation and lysosomal dysfunction in aged mice with progranulin deficiency.