Amyotrophic Lateral Sclerosis (ALS)
ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. As these nerve cells, or neurons, degenerate over time, a loss of muscle movement occurs causing those affected by ALS to eventually lose the ability to speak, eat, move, and breathe. The disease manifests in everyone differently: some may initially lose their fine motor skills, like the ability to write; some may have their first symptoms be excessive tripping or unexplained falls; others will experience slurred speech and difficulty swallowing.
Denali’s scientific approach to ALS
There is evidence that when the cells of the body are stressed by certain conditions such as infection, trauma, environmental factors, or certain ALS-associated genes this can initiate an integrated stress response, or ISR. This triggers inactivation of eukaryotic initiation factor, also referred to as eIF2B.
As part of the ISR process and inactivation of eIF2B, normal protein synthesis is interrupted and stress granules are formed, which may facilitate the accumulation of pathological clusters, known as TDP-43 clusters, typically seen in people with ALS. The accumulation of TDP-43 clusters in the central nervous system ultimately leads to nerve cell death, and is a common feature of many neurodegenerative diseases, including ALS.
Denali is studying DNL343, an investigational eIF2B activator treatment, that aims to impact the ISR. DNL343 is a small molecule that is proposed to activate the eIF2b – essentially turns off the ISR process, returning to normal protein synthesis. This eIF2B activation also leads to stress granules dissolving, a reduction of TDP-43 clusters, and the potential of restoring normal function of the nerve cells. DNL343 is being studied to determine if it may slow or stop the progression of neurodegeneration in ALS.
Denali is studying the effects and safety of DNL343 as part of the Phase 2/3 HEALEY ALS Platform Trial, in partnership with the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital and the Northeast ALS Consortium (NEALS).
Enrollment has completed for Regimen G, which is evaluating DNL343 in the HEALEY ALS Platform Trial.
To learn more about the HEALEY ALS Platform Trial, visit: MassGeneral.org
DNL343 is an investigational drug, its clinical profile has not been established, and it has not been approved by any global health authority.
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“Neurodegenerative diseases are notoriously difficult to study. We patients have a small window of time to communicate what we're experiencing before incapacity and death. The closer companies work with us, the greater their awareness of our experience, the shared sense of urgency, and the opportunity for breakthroughs in understanding our diseases.”
Seth - Individual living with ALS and Denali Patient Fellow
Advocacy Organizations
These organizations are committed to supporting the needs of people and families affected by ALS. Their websites may offer you more information, resources, and guidance.
By clicking these links, you will leave the Denali Therapeutics website and be redirected to a third-party site. Denali is not responsible for, nor does it endorse, the content, terms and conditions of use or privacy practices of external websites.
The mission of the ALS Association is to discover treatments and a cure for ALS and to serve, advocate for, and empower people affected by ALS to live their lives to the fullest.
ALS Network serves the nation’s largest local ALS community via a suite of comprehensive services including equipment loans, clinics, research navigation, benefits assistance, advocacy, events, and connection groups for all - caregivers, Spanish speakers, LGBTQIA+, veterans, and more.
ALS TDI is the world's foremost drug discovery lab focused solely on ALS.
Genetic ALS & FTD: End The Legacy is a patient-led organization dedicated to the needs and interests of the Genetic ALS & FTD community. This organization was born through the efforts and vision of dozens of people impacted by genetic ALS and FTD who collectively saw the need for the community's voice to be heard. In addition to patient advocacy, they provide educational and support information on their website.
Everything ALS is a patient-focused non-profit bringing technological innovations and data science to support efforts, from care to cure, for people with ALS.
Her ALS Story seeks to raise awareness about the impact of ALS on young women diagnosed before 35 and provide a community for them to connect, learn, and find support to live their best lives.
Hope Loves Company is the only national nonprofit organization serving children impacted by ALS Lou Gehrig's Disease. Their programs provide no-cost support, resources, and care for children ages 6-25, including family camp retreats, virtual hangouts led by mental health experts, and age-specific education to support children through their grief, loss, caregiving, and mental health journeys.
I AM ALS is a patient-led community that provides critical support and resources to those living with ALS, caregivers and loved ones.
This organization provides an international community for individual ALS/MND Associations globally. They build capability for their members and connect to external stakeholders.
NEALS’ mission is to rapidly translate scientific advances into clinical research and new treatments for people with ALS and motor neuron disease.
Target ALS is a medical research foundation committed to the search for effective treatments for ALS. They break down barriers to accelerate ALS research so that we can realize a world where everyone with ALS lives.
TRICALS is the largest European research initiative to find a cure for ALS. By bringing together patients (organisations), ALS experts from leading research centers and pharmaceutical companies, TRICALS internationally collaborates to accelerate and innovate clinical drug development for ALS.
Denali values all ALS community members and organizations. Additional resources may be available.
For questions, please contact the Denali Patient Advocacy team at patients@dnli.com.