medigraphic.com

2018, Number 5

<< Back Next >>

Rev Clin Esc Med 2018; 8 (5)

Más allá del riesgo cardiovascular: Rol de la - Simvastatina en enfermedades neurodegenerativas

Sequeira QCM, Casares FDA

Language: Spanish
References: 48
Page: 1-11
PDF size: 612.32 Kb.


ABSTRACT

Statins are derived from biological products, that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG- CoA) reductase stopping the conversion of HMG-CoA to mevalonate and producing a descent in serum cholesterol, its most renown effect. Reduction in serum levels of low density lipoproteins (LDL) has been a cornerstone in cardiovascular disease prevention. Statins are amongst the most popular, effective and used medicines towards that goal, not only for its effect in lipids but for its pleiotropic properties. The redirecting of the pharmaceutical industry and the lack of therapeutic resources against neurodegenerative diseases, supported by the biological mechanism of action of simvastatin has motivated research of this drug as an option for treating Alzheimer’s disease and secondary progressive multiple sclerosis. Successful results have been achieved in case control, cohort and phase II studies, however despite the optimism by the mechanism of action and its in vitro and in vivo effectiveness over different biomarkers, these positive results haven’t been replicated in a phase III study. Investigation on the topic remains very active.


REFERENCES

  1. 1.Bersot T. (2011). “Farmacoterapia de la hipercolesterolemia y la dislipidemia”. Obtenido de: http://accessmedicina.mhmedical.com.ezproxy. sibdi.ucr.ac.cr:2048/content.aspx?bookid=1882&sec tionid=138612427. 2.Rodriguez C, Obrador G. (2013) “Antihiperlipidémicos o hipolipemiantes”. Obtenido de: http://accessmedicina.mhmedical.com.ezproxy. sibdi.ucr.ac.cr:2048/content.aspx?bookid=1510&sec tionid=98010951.

  2. de Denus S, Spinler S. (2002).“Early Statin Therapy for Acute Coronary Syndromes”. Ann Pharmacother. 36(11):1749-58.

  3. Ray K, Cannon C. (2005). “The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes”. J Am Coll Cardiol. 8(46):1425-1433.

  4. Stone N, Robinson J, Lichtenstein AH, et al. (2013). “ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation”.

  5. Giovannoni G, Baker D, Schmierer K. (2015). “The problem with repurposing: Is there really an alternative to Big Pharma for developing new drugs for multiple sclerosis? Multiple Sclerosis and Related disorders” 4(1): 3-5.

  6. Arguedas J. (2014). “Aplicación de las nuevas guías de colesterol a una muestra basada en la población. Actualización Médica Periódica”. 155-04-14-AM.

  7. 8.Daroff R, Jankovic J, Mazziotta J et al. (2016). “Bradley’s Neurology in Clinical Practice. Seventh Edition. Chapter 95: Alzheimer and other Dementias”. Elsevier; 1380-1399.

  8. Elahi F, Miller B. (2017). “A clinicopathological approach to the diagnosis of dementia”. Nature Reviews Neurology. 13: 457-476.

  9. Winblad B, Amouyel P, Andrieu S et al. (2016). “Defeating Alzheimer’s disease and other dementias: a priority for European science and society”. The Lancet Neurology. 15 (5): 455-496.

  10. 11.Fassbender K, Simons M, Bergmann C. (2001). “Simvastatin strongly reduces levels of Alzheimer’s disease B-amiloid peptides AB42 and AB40 in vitro and in vivo”. Proc Natl Acad Sci U S A. May 8; 98(10): 5856–5861.

  11. McGuinness B, Craig D, Bullock R et al. (2014). “Statins for the treatment of dementia”. Cochrane Database Syst Rev. Jul 8;(7):CD007514

  12. Chen J, Chang C, Chang T et al. (2014). “Effects of statins on Incident Dementia in Patients with Type 2 DM: A population based retrospective cohort study in Taiwan”. PLoS One.9(2): e88434.

  13. Cooper S, Ademola T, Caslake M et al. (2016). “Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomized controlled trial”. Trials. 17: 370.

  14. Corrao G, Ibrahim B, Nicotra F. (2013). “Long Term Use of statins reduces the risk of hospitalization for dementia. Atherosclerosis”.230 (2): 171-176.

  15. Li G, Mayer C, Morelli D et al. (2017) “Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults”. Neurology. 89. 1-6. 17.Alzforum. Simvastatin. (2017). Obtenido de: http://www.alzforum.org/therapeutics/simvastatin.

  16. Simons M, Schwärzler F, Lütjohann, D et al. (2002). “Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: A 26-week randomized, placebo-controlled, double-blind trial”. Ann Neurol.Sep;52(3):346-50.

  17. Locatelli S, Lütjohann D, Schmidt H et al. (2002). “Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain”. Arch Neurol. Feb;59(2):213-6.

  18. Sjögren M, Gustafsson K, Syversen S et al. (2003). “Treatment with simvastatin in patients with Alzheimer’s disease lowers both alpha- and betacleaved amyloid precursor protein”. Dement Geriatr Cogn Disord. 16(1):25-30.

  19. Li G, Larson E, Sonnen J. (2007). “Stating therapy is associated with reduced neuropathologic chances of Alzheimer disease”. Neurology. Aug 28;69(9):878-85.

  20. Huang W, Li Z, Zhao L. (2017). “Simvastatin ameliorate memory deficits and inflammation in clinical and mouse model of Alzheimer’s disease via modulating the expression of miR-106b”. Biomed Pharmacother. Aug;92:46-57.

  21. Adeli S, Zahmatkesh M, Tavoosidana G et al. (2017). Simvastatin enhances the hippocampal klotho in a rat model of streptozotocin-induced cognitivedecline. Prog Neuropsychopharmacol Biol Psychiatry. Jan 4;72:87-94.

  22. Yamamoto N, Fujii Y, Kasahara R et al. (2016). “Simvastatin and atorvastatin facilitates amyloid B-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways”. Glia. Jun;64(6):952-62.

  23. Heon J, Sun K, Young J et al. (2015). “Dose-specific effect of simvastatin on hypoxia-induced HIF-1alfa and BACE expression in Alzhimer’s disease cybrid cells”. BMC Neurol.15: 127.

  24. Wang C, Chen T, Zhou L et al. (2015). “Simvastatin prevents β-amyloid(25-35)-impaired neurogenesis in hippocampal dentate gyrus through α7nAChR-dependent cascading PI3KAkt and increasing BDNF via reduction of farnesyl pyrophosphate”. Neuropharmacology. Oct;97:122-32.

  25. Clinical Trials. (2009). “Cholesterol Lowering Agent to slow progression (CLASP) of Alzheimer’s Disease Study”. Obtenido de: https://clinicaltrials. gov/ct2/show/NCT00053599?term=simvastatin&co nd=Alzheimer+Disease&rank=3

  26. Riekse R, Li G, Petrie E et al. (2016) “Effect of statins on Alzheimer’s disease biomarkers in cerebrospinal fluid”. J Alzheimers Dis. 10: 399–406.

  27. Clinical Trials. (2017) “Effects of simvastatin on Biomarkers (SimBio)”. Obtenido de: https:// clinicaltrials.gov/ct2/show/results/NCT01142336?te rm=simvastatin&cond=Alzheimer+Disease&rank=4

  28. Clinical trials. (2010). “Do HMG CoA Reductase inhibitors affect Abeta levels?” Obtenido de: https:// clinicaltrials.gov/ct2/show/NCT00303277?term=si mvastatin&cond=Alzheimer+Disease&rank=6 31.Zandl L, Danesh E, Sun Y. (2017). “Regulatory effects of simvastatin and apoJ on APP processing and amyloid B clearance in blood-brain barrier endothelial cells”. Biochim Biophys Acta. Sep 20. pii: S1388-1981(17)30201-9.

  29. 31.Zandl L, Danesh E, Sun Y. (2017). “Regulatory effects of simvastatin and apoJ on APP processing and amyloid B clearance in blood-brain barrier endothelial cells”. Biochim Biophys Acta. Sep 20. pii: S1388-1981(17)30201-9.

  30. Clinical Trials. (2017). “Endothelial Facilitation in Alzheimer’s Disease”. Obtenido de: https:// clinicaltrials.gov/ct2/show/record/NCT01439555?te rm=simvastatin&cond=Alzheimer+Disease&rank=1

  31. 33.Clinical Trials. (2015). “Evaluating Simvastatin’s Potential Role in Therapy (ESPRIT)”. .Obtenido de: https://clinicaltrials.gov/ct2/show/NCT00486044?te rm=simvastatin&cond=Alzheimer+Disease&rank=2

  32. Clinical Trials. (2017) “Statin effects on betaamyloid and cerebral perfusion in adults at risk of alzheimer’s disease (SHARP)”. Obtenido de: https:// clinicaltrials.gov/ct2/show/NCT00939822?term=si mvastatin&cond=Alzheimer+Disease&rank=5

  33. McGuinness B, Bullock R, Craig D. (2016). “Statins for the prevention of dementia”. Cochrane Database Syst Rev. Jan 4;(1):CD003160

  34. Valverde A, Vargas R, Parajeles A et al. (2015). “Guía Nacional para el Tratamiento de la Esclerosis Múltiple”. Neuroeje.28 (2): 69-120.

  35. Hauser L, Stephenson A. (2017). “Harrison’s Neurology in Clinical Medicine. 4th Edition. Chapter 45: Multiple Sclerosis and Other Demyelinating Diseases”. McGrawHill Education. 513-532.

  36. Rooper A, Samuels M, Klein J. (2014). “Adams and Victor’s Principles of Neurology. Chapter 36: Multiple Sclerosis and Other Inflammatory Demyelinating Diseases”. McGraw-Hill education.915-945.

  37. Ontaneda D, Thompson A, Fox R. (2017). “Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function”. Lancet; 389: 1357–66.

  38. Montalban X, Hauser S, Kappos L (2017). “Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis”. N Engl J Med. 376(3): 209-220.

  39. Roche. (2017). “Media Release: FDA approves Roche’s OCREVUS™ (ocrelizumab) for relapsing and primary progressive forms of multiple sclerosis”. Obtenido de: http://www.roche.com/media/store/ releases/med-cor-2017-03-29.htm

  40. FDA. (2017). “FDA Approves new drug to treat multiple sclerosis”. Obtenido de https://www.fda. gov/newsevents/newsroom/pressannouncements/ ucm549325.htm

  41. Kim W, Edler M, Kim S et al. (2015). “Oral Disease-Modifying Therapies for Multiple Sclerosis”. J ClinNeurol. Jan; 11(1): 9–19.

  42. Paul F. (2013). “Cladribine in múltiple sclerosis: pitfalls in a new treatment landscape. Expert Opinion on Pharmacotherapy”. 14(1)

  43. Chataway J, Schuerer N, Alsanousi et al. (2014). “Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebocontrolled, phase 2 trial”. Lancet. Jun 28;383(9936):2213-21.

  44. De Oliveira D, de Oliveira E, Ferrari F et al. (2015). “Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration”. Inflammopharmacology. Dec;23(6):343-54.

  45. Filippi M, Rocca M. “Simvastatin and cognition in multiple sclerosis”. Lancet Neurology; 16 (8): 572- 573.

  46. Ciurleo R, Bramanti P, Marino S. (2014). “Role of statins in the treatment of multiple sclerosis”. Pharmacol Res. Sep;87:133-143.

  47. Chan D, Binks S, Nicholas J et al. (2017). “Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebocontrolled trial”. Lancet Neurol. Aug;16(8):591-600.

  48. Generali J, Cada D. (2015). “Simvastatin: Multiple Sclerosis”. Hosp Pharm. Jun; 50(6): 464–466.




2020     |     www.medigraphic.com