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A system of neurons with glowing connections

Progressive supranuclear palsy (PSP) is a rare, progressive, and adult-onset neurological disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and the epidemiology of PSP is similar to that of ALS.1,2,3

PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial with several genetic and environmental factors likely contributing to tau dysfunction and aggregation.4,5,7,8

Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation.4,6

Tau pathology in turn drives neurodegeneration in PSP. The precise mechanism by which tau pathology drives neurodegeneration is still unclear though two processes are thought to contribute:6,7,9

  • Tau dysfunction leading to depolymerization of microtubules and axonal defects
  • Pathologic aggregation of abnormal tau leading to the formation of neurofibrillary tangles and widespread neuronal cell death and neurodegeneration in PSP

AMX0035 is proposed to simultaneously mitigate ER stress and mitochondrial dysfunction and hence, has the potential to influence PSP pathophysiology. Additionally, there is preclinical and clinical evidence to support investigation of AMX0035 in PSP.

Based on strong scientific rationale supporting AMX0035 in progressive supranuclear palsy (PSP), we initiated ORION (NCT06122662), a global, pivotal, Phase 3 trial of AMX0035 for the treatment of PSP. ORION is a double-blinded, placebo controlled, clinical trial to assess the impact of AMX0035 compared to placebo on disease progression as measured by the Progressive Supranuclear Palsy Rating Scale (PSPRS).

The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP, and advocacy groups.

  1. Golbe, L. I., & Ohman-Strickland, P. A. (2007). A clinical rating scale for progressive supranuclear palsy. Brain, 130(6), 1552–1565.
  2. Viscidi, E., Litvan, I., Dam, T., Juneja, M., Li, L., Krzywy, H., Eaton, S., Hall, S., Kupferman, J., & Höglinger, G. U. (2021). Clinical Features of Patients With Progressive Supranuclear Palsy in an US Insurance Claims Database. Frontiers in Neurology, 12.
  3. ‌Swallow, D. M. A., Zheng, C. S., & Counsell, C. E. (2022). Systematic review of prevalence studies of progressive supranuclear palsy and corticobasal syndrome. Movement Disorders Clinical Practice.
  4. ‌Coughlin, D. G., & Litvan, I. (2020). Progressive supranuclear palsy: Advances in diagnosis and management. Parkinsonism & Related Disorders, 73, 105–116.
  5. Park, H. K., Ilango, S. D., & Litvan, I. (2021). Environmental Risk Factors for Progressive Supranuclear Palsy. Journal of Movement Disorders, 14(2), 103–113.
  6. Shoeibi, A., Olfati, N., & Litvan, I. (2019). Frontrunner in Translation: Progressive Supranuclear Palsy. Frontiers in Neurology, 10.
  7. ‌Stamelou, M., Respondek, G., Giagkou, N., Whitwell, J. L., Kovacs, G. G., & Höglinger, G. U. (2021). Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies. Nature Reviews Neurology, 17(10), 601–620.
  8. ‌Stamelou, M., de Silva, R., Arias-Carrion, O., Boura, E., Hollerhage, M., Oertel, W. H., Muller, U., & Hoglinger, G. U. (2010). Rational therapeutic approaches to progressive supranuclear palsy. Brain, 133(6), 1578–1590.
  9. ‌Sarkar S. (2018). Neurofibrillary tangles mediated human neuronal tauopathies: insights from fly models. Journal of genetics, 97(3), 783–793.

Our commitment

At Amylyx, we are relentlessly driven by a commitment to those living with neurodegenerative diseases. We work collaboratively across everything we do, aspiring to help support and create more moments for the neurodegenerative community.


Our innovative approach to developing transformative therapeutics has far-reaching potential to improve the management of multiple neurodegenerative diseases. Learn more about our growing pipeline.