Recently, AFTD had a conversation with members of the Denali Therapeutics team, including Dr. Richard Tsai, to provide insights into their work to develop a therapeutic with Takeda to treat FTD-GRN (frontotemporal dementia caused by GRN gene mutations). Dr. Tsai is a neurologist at Denali where he partners with other scientists to design and conduct clinical trials on investigational drugs. Previously, he was an Assistant Professor of Neurology and Associate Director of Alzheimer’s Disease and Frontotemporal Dementia Clinical Trials Program at the UCSF Memory and Aging Center.

1. What approach is your company using to treat FTD?

Denali Therapeutics is dedicated to advancing treatments that target the underlying causes of frontotemporal dementia (FTD) associated with granulin (GRN) gene mutations. GRN mutations result in loss of up to half the normal amount of progranulin protein (PGRN) in the body. We are developing a PGRN replacement therapy (TAK-594/DNL593) designed to restore PGRN levels in the brain with IV injections. The hope of this investigational therapy is that it will slow down or halt disease worsening.

2. What do you think is the most urgent need to be addressed for people facing FTD and their families?

For families facing FTD support and awareness remain a critical need. While a top priority is a well tolerated, disease-modifying therapy to slow or halt disease worsening, there is also an immediate need to increase awareness of FTD. Greater awareness can support access to faster diagnosis and an appropriately supportive environment for the patients and their family. In a 2017 paper, Galvin and colleagues have shown this devastating disease causes more financial burden than other neurodegenerative diseases such as Alzheimer’s disease. At Denali, we recognize the pressing need for well tolerated, effective, disease-modifying therapies, and we’re committed to addressing these needs through our research, our partnerships (for example, with Takeda), and our collaborations with the FTD community to help bring hope and meaningful progress.

AFTD Note: With support from AFTD, a team of researchers led by James Galvin, MD, conducted an economic burden study analyzing the annual cost of caring for someone with FTD, including loss of income associated with FTD symptoms or a diagnosis. The team’s paper can be found here.

3. What role do you hope you and your colleagues play in empowering this community?

We see ourselves as both scientists and allies in the fight against FTD. Our role is to bring potentially groundbreaking therapies to clinical trials and, ultimately, to patients as quickly and responsibly as possible. We hope to lead and/or collaborate in a way that involves other biopharmaceutical companies, such as Takeda, nonprofits, and health agencies as a team effort is needed to combat this disease. We also recognize the importance of being transparent and listening to the community. We greatly appreciate the partnership with the AFTD and are committed to maintaining an open dialogue with the FTD community, sharing updates and gathering feedback to ensure our clinical trials and other programs match the need of patients/families. Empowerment for us means helping patients and families feel hopeful and connected to the scientific progress being made.

4. How do you think we can empower each other to reach our shared goals?

Empowerment comes from open communication and shared vision. By working closely with patient advocacy groups, sharing knowledge, and involving the community in our research journey, we create a strong network of support and collaboration.

5. What do you find to be the most encouraging about today’s research landscape?

When I first started working with patients with FTD as a clinician, just 10 years ago, I did not think there would be so many investigational medicine options so quickly. The pace of scientific progress and innovation in neurodegenerative disease research is incredibly encouraging. We’re also seeing an increase in collaboration between biotech, academia, and patient advocacy groups, which is very important in a rare disease like FTD. This collective effort means that hope is turning into tangible progress, and we are closer than ever to making a real impact on diseases like FTD.

6. What are the challenges you see, and what are your hopes for how stakeholders can overcome these together?

One of the greatest challenges is the complexity and rarity of FTD itself. FTD is a multifaceted disease that requires tailored approaches for different patient populations. Awareness that FTD is not a single disease but rather a group of related disease with more than one potential cause can encourage the community to seek more medical assistance that can lead to better diagnosis, support and knowledge of clinical trials. Additionally, access to clinical trials, especially for rare conditions like FTD, can be difficult for many families. Many trials are taking longer than planned to reach their enrollment, and in turn provide answers to key scientific questions. We believe that by working together—biotech companies, academic researchers, healthcare providers, and patient advocacy groups—we can overcome these hurdles.

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

A genetic counselor can evaluate the likelihood that your condition, or your family’s condition, has a genetic cause and can help you think through the specifics of genetic testing and how to talk to family members about the testing process, privacy concerns, and more. For people who are interested in pursuing testing, the counselor will discuss its risks and benefits and identify the specific test that can ensure the most accurate results possible. More information about genetic counseling can be found here.

AFTD sincerely appreciates Denali Therapeutics’ and Takeda Pharmaceuticals’ continued support of our mission and the people we serve.