Recently, Prevail Therapeutics presented interim results from their Phase 1/2 open-label clinical trial assessing the safety and efficacy of their gene therapy to raise progranulin levels in people with FTD-GRN. Not only was the treatment generally safe and well-tolerated among participants, but progranulin levels in the cerebrospinal fluid increased immediately following a one-time administration and remained at normal or above-normal levels after 12 months.

Concurrently, the trial also evaluated a product of lysosomal lipid metabolism – a process believed to be implicated by deficient progranulin levels and significant to FTD pathology – as an indicator, or biomarker, of PR006’s efficacy in not only restoring progranulin levels but amending downstream processes. Trial data show that this biomarker, which can be collected via urinalysis, may reflect lysosomal dysfunction, and therefore indicate disease. More research is required to understand if restoring progranulin and downstream processes meaningfully impacts FTD symptoms.

AFTD spoke with Prevail Therapeutics Vice President of Clinical Development Olga Uspenskaya, MD, PhD, about this intervention, empowering the FTD community, and the current state of FTD research. The conversation below has been edited and condensed.

What approach is your company using to treat FTD?
Our intervention, PR006, is designed to treat the root cause of FTD-GRN, which is caused by a mutation that results in progranulin deficiency, by delivering a healthy gene through a one-time injection using well-established viral vector technology. By this method, we hope to get an individual’s body to produce and restore healthy levels of progranulin – critical for normal functioning of the brain – thereby preventing or slowing down neurodegeneration. Our approach is directed at the source of the disease’s pathology.

What do you think is the most urgent need for persons diagnosed and their families?
Currently, only symptomatic treatments for FTD are available – there is nothing available to effectively treat the disease itself as it occurs in the brain.

Additionally, we all know and have learned from other neurodegenerative disorders that early diagnosis is critical for any treatment to be successful. We have a long way to go in FTD, which is still very much underdiagnosed due to many limiting factors and disparities, such as a person’s geographic location, different access to healthcare providers, and socioeconomic status, as well as a limited number of experts and need for improved awareness about FTD among general neurologists.

What role do you hope you and your colleagues play in empowering the FTD community?
I think we can contribute to educating the general population, the patient community, and medical professionals. We all need to understand there is a lot of stigma associated with FTD, which we need to come together to address, enabling people to get an accurate diagnosis so they can seek help earlier.

As there is more collaboration among stakeholders, it should also be our mission to work together and foster precompetitive partnerships to discover and develop FTD biomarkers, which will open the door for future treatments and early diagnosis of sporadic forms of the disease. Right now, I believe we are in good shape to diagnose someone when a genetic cause can be found, but without robust biomarkers for subtypes, we’ll never be able to improve diagnosis in cases of sporadic FTD.

What is most encouraging about today’s research landscape?
I am amazed by how quickly FTD research has increased, though I’m not sure the field was prepared for the growth. It’s great to see, but we must work together to overcome shared challenges such as patient recruitment and access to genetic testing. [AFTD strongly encourages anyone considering genetic testing to first consult with a genetic counselor.]

Currently, with so many clinical trial options available, there are multiple shots on goal for FTD-GRN, which is encouraging because what we’re seeing for people affected by one form of FTD will hopefully be replicated for others who are living with the C9orf72 and MAPT variants, as well as people with sporadic forms of the disease.

If you’d like to learn more about Prevail Therapeutics’ work, please visit their website.