Ongoing clinical trials provide hope for the most common form of early-onset dementia

Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD) is a rare, rapidly progressing neurodegenerative disease and is the most common form of dementia in people under 60 years of age. FTD affects the frontal and temporal lobes of the brain, areas generally associated with personality, behavior, and language. Therefore, people with FTD often develop symptoms such as behavior changes, lapses in judgment, and severely decreased language skills when they are in their 40s and 50s. Unlike Alzheimer’s disease, which is characterized primarily by memory problems but usually without major changes in personality or language, FTD attacks the core of what makes us who we are.

Because FTD is a rare condition, estimated to affect <0.02% of the population in the United States and the European Union, it is easy for people presenting with FTD symptoms to be misdiagnosed as having a psychiatric or other disorder. most common form of dementia such as Alzheimer's disease. Additionally, some of the cognitive, behavioral, and language difficulties in FTD may go unrecognized or may be stigmatizing and embarrassing for individuals and their families. As a result, the path to an accurate diagnosis is often long and complicated for FTD patients and their families. To make matters worse, once a diagnosis of FTD is received, there are currently no approved treatment options available for any form of FTD.

The good news is that there are now multiple interventional clinical trials evaluating potential investigational therapies for the treatment of different types of FTD. A subset of FTD cases are genetic or hereditary in nature, meaning that a parent can pass a genetic variant associated with FTD to his or her child. The 3 most common genes that have been associated with the development of FTD are GREEN (progranulin gene), C9orf72Y Map. In the past, genetic testing for variants of these genes was less common; however, now that potential therapies are being developed to address the underlying problems associated with each of these different gene variants, genetic testing is becoming more common and important than ever to help carriers of these variants learn what type of investigational therapy is most appropriate. for them. There are several options available for people to receive genetic counseling and genetic testing at no cost. The Association for Frontotemporal Dementia (AFTD) is a great resource for people interested in genetic testing.

Ongoing Clinical Trials at FTD

Once a person knows their genetic status, they may be eligible to participate in a clinical trial of an investigational therapy that is designed to slow or stop disease progression in that specific FTD genetic subtype. There are several ongoing intervention trials which are listed below by genetic subtype.


    • we in allector, are conducting a Phase 3, double-blind, placebo-controlled study evaluating the efficacy and safety of an intravenously administered monoclonal antibody (AL001) in participants who are at risk of or who have been diagnosed with FTD because they have a mutation in the progranulin gene
    • Therapeutic Prevail is conducting a phase 1/2, open-label, ascending-dose, first-in-human study that will evaluate the safety and effect of intracisternal administration of an investigational gene therapy (PR006) on progranulin levels in FTD patients with a mutation in the progranulin gene
    • biographical passage is conducting a Phase 1/2 open-label, single-arm, dose-escalation study on the safety, tolerability, and efficacy of intracisternal administration of an investigational gene therapy (PBFT02) on progranulin levels in FTD patients with a mutation in the progranulin gene
    • Denali Therapeutics is conducting a phase 1/2, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL593 in healthy volunteers and patients with FTD with a mutation in the progranulin gene


      • transposon therapeutics is conducting a phase 2a, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of a LINE-1 reverse transcriptase inhibitor (TPN-101) in patients with amyotrophic lateral sclerosis (ALS) and/or FTD Associated with Hexanucleotide Repeat Expansion in the C9orf72 Gene (C9ORF72 ALS/FTD)
      • wave life sciences is conducting a randomized, double-blind, placebo-controlled phase 1b/2a study to evaluate the safety, tolerability, PK and PD of intrathecal administration of an antisense oligonucleotide (WVE-004) in adult patients with ALS or FTD associated with C9orf72

There is a tremendous unmet medical need to develop effective therapies for FTD, and this is an exciting time with multiple studies of potential new treatments underway. Participation in clinical intervention trials is essential to bring new therapies to market. Anyone who has been diagnosed with FTD or has a potential family history of FTD and is interested in genetic testing and clinical trial opportunities can learn more at the links above.

Photo: Andrews, Getty Images

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