Over the past few years, we have seen a significant and encouraging rise in clinical trials focused on frontotemporal dementia (FTD), particularly those targeting genetic forms of the disease. This growing research effort is an important step toward a better understanding of FTD and, ultimately, toward developing effective treatments.
Why this matters for GENFI families
This blog explains what researchers are testing, what recent results mean, and what may come next!
But first, what are Clinical Trials?
Clinical trials are research studies that test new treatments in people. Before a drug can become widely available, it must go through a careful step-by-step process to check that it is safe, well tolerated, and effective.
Clinical trials usually happen in stages:
- Preclinical: The treatment is tested in cells and animals.
- Phase 1: Tests safety and dosing in a small number of people.
- Phase 2: Looks more closely at safety and early signs of effectiveness.
- Phase 3: Tests whether the treatment works in a larger group over a longer period of time.
- Phase 4: Takes place after approval and monitors long-term effects.
Ongoing Trials in FTD: Targeting Progranulin Mutations
Many current FTD trials focus on people with changes in the progranulin (GRN) gene. These genetic changes usually lead to about half the normal level of progranulin protein in the body.
This happens because one copy of the GRN gene is not working properly, meaning every cell in the body produces less progranulin.
Why is progranulin important?
Research suggests that increasing progranulin levels may help:
- 🧠 Reduce disease-related pathology (less damage to brain cells and connections)
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🛡️ Improve immune system responses (healthier support from the brain’s immune system)
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🔥 Decrease brain inflammation (reduced harmful inflammation in the brain)
As a result, current clinical trials for people with GRN mutations aim to increase progranulin levels. The hope is that restoring these protein levels may help slow – or potentially prevent – the progression of FTD in individuals who are genetically at risk.
Recent Trial Updates
INFRONT-3 (Alector)
The first-ever Phase 3 clinical trial in genetic FTD has now completed!
This study tested a drug called latozinemab (AL001) in people with FTD caused by a GRN mutation. Latozinemab is given by infusion straight into the blood and works by blocking a receptor called sortilin, which normally breaks down progranulin. By blocking sortilin (as shown in the diagram), the treatment stops progranulin from being broken down, aiming to increase its levels in the body and brain.
The study found that:
- Progranulin levels increased as expected
- The treatment was generally safe
However, the treatment did not lead to improvements in thinking, behaviour, or brain changes on scans, and it did not slow disease progression compared with placebo.
What does this mean for Patients and Families?
While disappointing, this study marked an important milestone. It showed that large Phase 3 trials in genetic FTD are possible and provided valuable insights to guide future research into progranulin-based treatments.
You can read the full outcome report here.
Vesper BIO
This study tested the safety and effects of a new drug called VES001 and how the body responds to it. Like the Alector study, the goal is to increase progranulin levels in people with a GRN gene change.
Unlike some other treatments, VES001 is taken as a capsule by mouth. It also works by changing how the protein sortilin behaves. Sortilin normally lowers progranulin levels; by modifying it, VES001 helps bring progranulin levels back toward normal.
Early results have been very encouraging:
- At the higher dose tested, progranulin levels in spinal fluid increased by more than 95%
- This is important because people with a GRN mutation usually start with much lower levels
UCLH recruited the first participant worldwide into this study!
Because of these promising findings, plans are now in place to move VES001 into the next stage of trials (Phase 2b/3). We will continue to share updates as the study progresses!
What does this mean for Patients and Families?
This study shows that an oral treatment can safely increase progranulin levels – an important early step towards potential future treatments.
You can read the whole outcome report here
AviadoBio
One final update we would like to share comes from an early-stage clinical trial run by AviadoBio. This study is testing a one-time gene therapy delivered directly to the brain through a specialist surgical procedure. The treatment is given to a specific brain region called the thalamus, which connects to many areas affected in FTD. To see an animation of how this procedure works – produced by AviadoBio, click here!
This therapy aims to address the underlying genetic cause of the disease. It uses a harmless virus (called a viral vector) to deliver a healthy copy of the gene into brain cells. This allows the cells to start making the working protein again, leading to more progranulin protein.
This is a new and early-stage approach and is being carried out at specialist centres. In the UK, the study site is Cardiff University Hospital.
In 2025, an important milestone was reached when the first UCL/UCLH participant received gene therapy for a neurodegenerative disease as part of this study!
One of our team members had the opportunity to observe the procedure, offering a first-hand insight into the immense amount of work involved in delivering this type of therapy. From the detailed planning that takes place long before surgery to the careful mapping of infusion pathways within the
This is a five-year study, and participants who take part will be followed and assessed throughout this period to see whether any changes are observed over time. While the full results will not be available until the study is complete, we hope to begin seeing early data along the way – particularly in relation to safety and biological markers that may help us better understand the effects of the treatment.
What does this mean for Patients and Families?
This study is testing a bold, one-time approach that aims to address the genetic cause of FTD. While it is still at an early stage, it represents a promising step toward developing treatments that could change the course of the disease.
In summary
Research into genetic FTD is moving forward on multiple fronts – including tablets, infusions, and gene therapy. While not every study leads to a new treatment, each trial adds essential knowledge and helps shape what comes next.
For GENFI families, this ongoing research reflects real progress, careful learning, and continued commitment to understanding and treating FTD.
This blog has summarised the main clinical trial updates currently taking place at UCL, which are currently all targetted specifically on progranulin (GRN) mutations. However, for details about other ongoing genetic FTD trials can be found on the GENFI trials page on our website (linked here).
If you are interested in finding out more or being involved in familial FTD trials, please contact genfi@ucl.ac.uk
Sophie, on behalf of the FTD talk team.
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