Reata PharmaceuticalsDiseases We TargetDisease Education

Introduction

Reata is committed to developing novel therapeutics for patients with serious and life-threatening diseases. AS, FA, and PAH are diverse, chronic diseases in which mitochondrial dysfunction, inflammation, and oxidative stress are implicated. Mitochondrial dysfunction occurs when cellular energy production is impaired in favor of production of proinflammatory mediators including cytokines and ROS. Chronic inflammation can lead to tissue fibrosis, organ remodeling, or other organ damage.1

Alport Syndrome (AS)

  • AS is the second most common inherited cause of kidney failure and affects as many as 60,000 people in the US.9 90% of men with X-linked AS develop ESRD before age 40.10 Approximately 12% of women with X-linked AS develop ESRD by age 40, and this increases to 40% by age 8011,12
  • It is caused by a genetic disorder in which type IV collagen defects alter the structure and function of the glomerular basement membrane, the kidney’s main filtering apparatus.10 Treatment approaches include annual monitoring, supportive care, diet, lifestyle management, and off-label use of blood pressure-lowering therapies approved for other forms of CKD. There is a significant unmet need for additional therapies13-16

Friedreich’s Ataxia (FA)

  • FA is an inherited, progressively debilitating degenerative neuromuscular disorder for which there are no approved therapies.17 FA affects approximately 6000 individuals in the US and 22,000 globally.18,19  Many individuals with FA succumb to their disorder at an early age.20 Currently, FA management is aimed at alleviating symptoms and maintaining optimum functioning17

Connective Tissue Disease-Associated Pulmonary Arterial Hypertension (CTD-PAH)

  • CTD-PAH is often a late and fatal occurrence in individuals with CTD.21  Between 10% and 15% of patients with scleroderma or lupus erythematosus, for example, have CTD-PAH.22-25  In the US, the 5-year survival for CTD-PAH is approximately 44%, while the survival of PAH from other causes is substantially greater.26

Autosomal Dominant Polycystic Kidney Disease (ADPKD) (coming soon)

References
  1. Gilroy D, De Maeyer R. New insights into the resolution of inflammation. Semin Immunol. 2015;27(3):161-168.
  2. Imig JD, Ryan MJ. Immune and inflammatory role in renal disease. Compr Physiol. 2013;3(2):957-976.
  3. Tecklenborg J, Clayton D, Siebert S, Coley SM. The role of immune system in kidney disease. Clin Exp Immunol. 2018;192(2):142-150.
  4. Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B. Oxidative stress in chronic kidney disease [published online August 13, 2018]. Pediatr Nephrol. doi: 10.1007/s00467-018-4005-4.
  5. Flemming NB, Gallo LA, Forbes JM. Mitochondrial dysfunction and signaling in diabetic kidney disease: Oxidative stress and beyond. Semin Nephrol. 2018;38(2):101-110.
  6. Bello-Klein A, Mancardi D, Araujo AS, Schenkel PC, Turck P, de Lima Seolin BG. Role of redox homeostasis and inflammation in the pathogenesis of pulmonary arterial hypertension. Curr Med Chem. 2018;25(11):1340-1351.
  7. Scott TE, Kemp-Harper BK, Hobbs AJ. Inflammasomes: A novel therapeutic target in pulmonary hypertension [published online May 30, 2018]? Br J Pharmacol. doi: 10.1111/bph.14375.
  8. Paupe V, Dassa EP, Goncalves S, et al. Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS One. 2009;4(1):e4253.
  9. Alport Syndrome Foundation. What is Alport syndrome? http://alportsyndrome.org/what-is-alport-syndrome. Accessed November 8, 2018.
  10. Kashtan CE, Ding J, Gregory M, et al. Clinical practice recommendations for the treatment of Alport syndrome: A statement of the Alport Syndrome Research Collaborative. Pediatr Nephrol. 2013;28(1):5-11.
  11. Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: Natural history and genotype-phenotype correlations in girls and women belonging to 195 families: A “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol. 2003;14(10):2603-2610.
  12. Kashtan CE, Ding J, Garosi G, et al. Alport syndrome: a unified classification of genetic disorders of collagen IV a345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int. 2018;93:1045-1051.
  13. Kovács G, Kalmár T, Endreffy E, et al. Efficient targeted next generation sequencing-based workflow for differential diagnosis of Alport-related disorders. PLoS One. 2016;11(3):e0149241.
  14. Alport Syndrome Foundation. 4 ways patients living with Alport syndrome can stay healthy. http://alportsyndrome.org/alport-syndrome-males/4-ways-patients-living-with-alport-syndrome-can-stay-healthy/. Accessed November 8, 2018.
  15. Alport Syndrome Foundation. The renal diet: Potassium. http://alportsyndrome.org/blog/the-renal-diet-potassium/. Accessed November 8, 2018.
  16. Savige J, Gregory M, Gross O, et al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol. 2013;24(3):364-375.
  17. Aranca TV, Jones TM, Shaw JD, et al. Emerging therapies in Friedreich’s ataxia. Neurodegener Dis Manag. 2016;6(1):49-65.
  18. Vankan P. Prevalence gradients of Friedreich’s ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge. J Neurochem. 2013;126(suppl 1):11-20.
  19. Polek B, Roach MJ, Andrews WT, Ehling M, Salek S. Burden of Friedreich’s ataxia to the patients and healthcare systems in the United States and Canada. Front Pharmacol. 2013;4:66.
  20. Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: Classical and atypical phenotypes. J Neurochem. 2013;126(suppl 1):103-117.
  21. Pulmonary Hypertension Association. Types of pulmonary hypertension. http://phassociation.org/patients/aboutph/types-of-ph/. Accessed November 8, 2018.
  22. Galié N, Manes A, Farahani KV, et al. Pulmonary arterial hypertension associated to connective tissue diseases. Lupus. 2005;14(9):713-717.
  23. Khanna D, Gladue H, Channick R, et al. Recommendations for screening and detection of connective-tissue disease associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):3194-3201.
  24. Hsu VM, Chung L, Hummers LK, et al. Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in scleroderma (PHAROS) cohort study. Semin Arthritis Rheum. 2014;44(1):55-62.
  25. Pérez-Peñate GM, Rúa-Figueroa I, Juliá-Serdá G, et al. Pulmonary arterial hypertension in systemic lupus erythematosus: Prevalence and predictors. J Rheumatol. 2016;43(2):323-329.
  26. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest. 2012;142(2):448-456.
View References
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