AFTD recently spoke with Alector Chief Medical Officer Gary Romano, MD, PhD, about his colleagues’ work to develop an approved therapeutic to treat FTD and his hopes for the future of therapeutic development.

Responses have been edited for clarity and length.

Can you share some background on Alector’s approach to developing an FTD-focused therapeutic?

Alector’s therapeutic strategy is to harness the brain’s immune system to combat neurodegenerative diseases including FTD and Alzheimer’s disease (AD). Our approach is rooted in genetics of neurodegenerative diseases. As research progressed over the past decades, researchers discovered several gene mutations that increase risk for developing a neurodegenerative disease by affecting microglial function. At Alector, our work focuses on targeting proteins that regulate microglial activity.

AFTD note: Microglia are non-neuronal cells located in the brain and spinal cord that are key to the central nervous system’s immunity.

Microglia play important roles in maintaining normal brain function and the health of neurons, vital cells in the brain. They are responsible for clearing harmful and damaged proteins and cells, and maintaining an effective immune system in the brain. They also contribute to the overall health of the brain vascular system and connections between brain cells.

Research suggests that through normal aging processes, there is decreased effectiveness of the brain’s immune system. This decrease in brain immunity potentially contributes to increased brain vulnerability and susceptibility to developing a neurodegenerative disease. We believe that by boosting or modifying microglial function, we may be able to restore and protect normal brain function. Our goal is to shift microglia to be more effective.

What inspires you and your colleagues to work in the FTD and neurodegenerative disease space?

For me, studying neurodegenerative disease and participating in the investigation and discovery of therapies has been a life-long ambition. I started off working at the lab bench, where I moved into directing clinical trials focused on neurodegenerative diseases – particularly Alzheimer’s disease – and I’m also a practicing neurologist where I see people who are diagnosed with FTD. In addition to that, my mother passed away following a long decline with dementia, so the battle against neurodegenerative disease is a very personal one.

Speaking for my colleagues at Alector, our entire focus is to bring effective treatments to people who are facing FTD and related neurodegenerative diseases. Every time we hear from people, or I meet with someone who’s living with a diagnosis, we see lives turned upside down. We learn about the emotional, physical, and economic impact these diseases have on people and families – and we are inspired to continue our work.

What do you hope people will learn and understand about FTD? 

First, we need to make sure the public and practitioners become more aware of FTD and how it presents clinically. While progress has been made in recent decades to understand and bring attention to FTD, it is still too often underdiagnosed or misdiagnosed. People may shrug this off, but the lack of recognition is becoming increasingly critical. Some physicians believe there is nothing to be done for a person with FTD – so people are not getting an accurate diagnosis and don’t know they have options available to them, such as being eligible to join a clinical trial.

Now, more than ever, we need people to know about this disease and have people accurately diagnosed because there are therapeutics in clinical trials. I want to stress that participation of eligible volunteers in clinical trials is the only path we have to identify effective treatments for FTD. Without trial participants, we won’t be able to tell if these therapies work.

We are in a heyday of FTD-focused clinical trials – there’s been a surge of interest among researchers because advances in science have led to potential, testable hypotheses on how to treat this disease and may provide people with hope. But if companies are not able to enroll people in a timely way, they are going to come to the conclusion that FTD is too hard to study. Without more knowledge of this disease, any progress we’ve made is impeded.

This year, AFTD is focused on making sure every FTD story counts. Why do you think it is important for people to share their stories?

Sharing people’s stories about FTD is crucial to raising awareness. Today, many people still don’t know what “FTD” means. It’s so underrecognized, which is likely to do with how it presents first as changes in behavior and language skills. People – including clinicians – often confuse these symptoms with those of psychiatric disorders or a stroke. That’s a real problem, because the longer it takes for a person to be diagnosed with FTD, the less likely they will be to have access to ongoing clinical trials or effective therapies when they are available.

Medical science tells us treating chronic diseases like FTD as early as possible, before organ damage, is likely to be more effective. Unfortunately, given the typical delay in recognizing that a person has FTD, there is often widespread tissue damage and neuronal loss by the time people are being diagnosed.

Personal stories are important because it’s the story of who that person was before the disease. We also learn what happened, what did the families notice, and how long did it take them to get to the right doctor? Word has to get out there to people, families, general practitioners, and specialists so that the early signs aren’t overlooked, dismissed, or ruled out.

We can’t continue to assume these symptoms are psychiatric disorders. The more we talk about the disease, we can also help raise resources that are desperately needed for people – not only in terms of discovering treatments, but to improve the overall infrastructure around patient, care partner, and family support.

What are your hopes or visions for the future of FTD and the neurodegenerative disease landscape? 

My vision for the future of caring for people with neurodegenerative disease – particularly FTD – is that healthcare professionals at all levels will be able to easily recognize presenting symptoms and diagnose people earlier in the disease process, identifying them for participation in clinical trials for potential treatments.

Right now, following decades of research to better understand the biology of neurodegenerative disease and disease biomarkers, the best option is to be able to slow or stop a disease process before it progresses too far, but we must get people identified as early as possible.

I also hope that there will be more genetic screening for most, if not all, people with FTD. With genetic screening, people will know if they are eligible for specific treatments, and we get a clearer picture of family histories and patterns of autosomal dominant inheritance (in which dominant genes, which can include mutations, are passed from parent to child), which we often lack because FTD is still so underdiagnosed.

More comprehensive information from genetic testing can potentially enable better treatment responses or opportunities for disease prevention. This will lead to a world where FTD is identified early in a person’s life and treatment can start before symptoms appear or before there is irreversible damage. We can potentially spare families the devastating impact of FTD.

AFTD note: Whether you have a personal or family history of FTD, or whether past misdiagnosis could potentially be masking one, consider genetic counseling as a first step to answering questions about your genetic status.

A genetic counselor can evaluate the likelihood that you or your family’s condition has a genetic cause, and can help you think through the benefits and risks of genetic testing and ways to talk to family members about genetic testing, privacy concerns, and more. For individuals who are interested in genetic testing, the genetic counselor will discuss the risks and benefits of testing, and identify the specific test that can ensure the most accurate results possible. For more information about the genetics of FTD, click here.

AFTD sincerely appreciates Alector’s long-standing commitment to our mission, and we are grateful for their continued support of our annual Education Conference. If you are attending this year’s conference, whether in person or virtually, and you’d like to learn more about Alector’s work, please be sure to visit their table in the Exhibitor Hall or their virtual booth on the AFTD app.

 

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