The Potential of Orexin Science: Searching for a Novel Approach to Treat Narcolepsy Type 1

Neurological diseases can rob us of the essence of what it means to be human. For people living with narcolepsy type 1 (NT1), they may experience a range of symptoms that can significantly affect many aspects of daily life.^1-4

As NT1 is a rare disease, it was not a condition I saw often during my time as a sleep physician, which made it challenging to understand the full patient experience.² Hearing stories of people with NT1 from my time in the clinic and since joining Takeda has opened my eyes to the holistic impact the disease can have on those individuals beyond an abnormal need for sleep.

People with NT1 have repeated transitions between periods of wakefulness and sleep throughout the day, resulting in excessive daytime sleepiness (EDS) where individuals may have uncontrollable lapses into sleep.^5,6 A distinctive characteristic of NT1 is cataplexy, a brief loss of muscle tone provoked by strong emotions ranging from facial weakness to full body collapse.² Some individuals with NT1 report challenges working or performing as well as hoped in school, along with managing daily activities such as driving, exercising or socializing with friends and family.^3,4 Individuals with NT1 have experienced stigma related to their narcolepsy as they may be viewed as lazy or unmotivated, and the fear of cataplexy triggers may lead to social isolation as well.^4,7

People with narcolepsy may fear sleep paralysis and hallucinations.⁸ The disturbing nature of these symptoms are not always a focus of discussion or known to the wider community. Beyond those core symptoms, these individuals may have cognitive symptoms, such as difficulty thinking clearly, remembering, concentrating and paying attention.³ Collectively, the daytime and nighttime symptoms of the disease contribute to physical, psychological and social limitations that create a significant impact for those living with this disease.^9,10

The Critical Scientific Discovery of the Orexin Pathway 

In the last 25 years, the orexin system was discovered and linked to the underlying cause of NT1.⁵ Orexins have been found to be key regulators of sleep and wake cycles, and may also affect other functions including attention, mood, metabolism and respiratory function.^5,11-15

The role of orexin in sleep regulation was discovered through foundational work by Masashi Yanagisawa’s group at University of Tsukuba, Emmanuel Mignot’s group at Stanford University and Jerome Siegel’s group at the University of California, Los Angeles. This research found that orexin-producing neurons were absent in people with NT1, establishing a mechanistic cause for a multitude of symptoms.¹⁶ These discoveries paved the way for researchers, including those at Takeda’s labs in Shonan, Japan, to understand orexins as potential therapeutic targets for NT1. 

For the last two decades, we have been researching within the orexin science space, exploring its potential in NT1. Takeda does not have any approved therapies for narcolepsy, and while we are committed to advancing research in this area, future approval cannot be assured. 

Innovation Across the Patient Journey

Meeting the needs of the narcolepsy community requires more than just therapeutic innovation. Takeda, in collaboration with the physician and patient community, has focused efforts on uncovering the true impact of the disease and understanding the long and complicated diagnosis journey. Through comprehensive, real-world evidence generation, the Global Evidence & Outcomes Team at Takeda has been able to better understand more completely the social, emotional, physical and economic impact of NT1. Leveraging these insights enabled us to create a first-of-its-kind framework that we are applying in our clinical studies. This framework aims to assess the daily impact of living with NT1, with the goal of informing researchers, patients and providers in the hopes of improving disease management and enhancing patient outcomes. From a diagnosis perspective, our Translational Sciences and Data Digital & Technology teams are collaborating with academia and industry partners to explore the development of digital tools as well as fluid biomarker tools aimed at improving the differential diagnosis of NT1 from other sleep-wake disorders and helping guide disease management. 

It is an exciting time for those of us working in the rare sleep-wake disorder space. The renewed interest in sleep hygiene and the connection to brain health has prompted more open discussion around the importance of sleep and when to seek help. Building on this momentum, we are leveraging orexin science to explore innovative approaches for disease monitoring and management in individuals living with NT1. 

We encourage anyone specializing in sleep disorders to follow our progress and stay connected to updates and announcements from our orexin franchise. To learn more about our efforts, please visit Takeda.com. 

While this article is accessible to the general public for disease awareness purposes, it should not be used to diagnose or treat any condition. Please consult your healthcare provider for personalized medical advice.