In vivo studies support the pursuit of a therapy in amyotrophic lateral sclerosis (ALS) that targets the terminal complement pathway.1

In a space where the promise of a therapeutic solution has remained frustratingly out of reach, Ra remains undeterred. Explore our view of the opportunities that exist for the people with ALS who so desperately need them. Ground yourself in the facts to see why Ra is committed to this patient population.

Behind the statistics are the patients and their families facing the daily realities of this diagnosis.

ALS is a condition of severe, progressive neuromuscular deterioration that leads to paralysis of voluntary muscles and eventual death.5 Patients experience persistent weakness, painful muscle cramps, or spasticity in their limbs.6,7 As the disease progresses, it becomes difficult to swallow and breathe without assistance.7

In the face of the difficult clinical reality of the disease, a deeper understanding of the mechanism of disease may offer a scientific pathway for areas of therapeutic research.

ALS pathology is associated with complement protein deposition.

Although the exact mechanism of ALS remains elusive, new research suggests a connection between aberrant complement activation and the pathophysiology of the disease.7

In vivo studies support a possible therapeutic role for targeting the terminal complement pathway.1

In animal models, targeting complement delayed disease progression and extended survival.

  • The C5a receptor (C5aR1) was upregulated in the motor neurons of transgenic SOD1G93A mice and postmortem tissue from ALS donors.8,9,10
  • Knock out C5aR1 or pharmacologic inhibition of C5aR1 prolonged survival in animal models.9

We are proud to fight for your patients through research.

References: 1. Bahia El Idrissi N, Bosch S, Ramaglia V, Aronica E, Baas F, Troost D. Complement activation at the motor end-plates in amyotrophic lateral sclerosis. J Neuroinflammation. 2016;13:72. 2. ALS Association. Epidemiology of ALS and suspected clusters. Accessed July 8, 2019. 3. Sorenson EJ, Stalker AP, Kurland LT, Windebank AJ. Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925 to 1998. Neurology. 2002;59(2):280-282. 4. ALS Association. Causes/inheritance. Accessed July 8, 2019. 5. Mehta P, Kaye W, Raymond J, et al. Prevalence of amyotrophic lateral sclerosis—United States, 2014. MMWR Morb Mortal Wkly Rep. 2018;67:216-218. 6. Hardiman O, Al-Chalabi A, Chio A, Corr E, Logroscino G, Robberecht W, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071. 7. Kjældgaard AL, Pilely K, Olsen KS, et al. Amyotrophic lateral sclerosis: The complement and inflammatory hypothesis. Mol Immunol. 2018;102:14-25. 8. Humayun S, Gohar M, Volkening K, et al. The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons. J Neuroimmunol. 2009;210(1-2): 52-62. 9. Woodruff TM, Costantini KJ, Crane JW, et al. The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol. 2008;181(12):8727-8734. 10. Lee JD, Kamaruzaman NA, Fung JN, et al. Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis. J Neuroinflammation. 2013;10:119.