Skip to main content

Advertisement

Log in

The potential protective effect of tramiprosate (homotaurine) against Alzheimer’s disease: a review

  • Review Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Due to the progressive aging of the population and to the age-associated increase in its incidence, Alzheimer’s disease (AD) will become in near future one of the major challenges that healthcare systems will have to face with in developed countries. Since the pathophysiological process of AD is thought to begin many years before the clinical diagnosis of dementia, in theory there is an opportunity for preventive therapeutic interventions. In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, in the beneficial effects of some natural compounds in preventing various age-related pathologic conditions, including brain aging and neurodegeneration. Homotaurine, a small aminosulfonate compound that is present in different species of marine red algae, has been shown, in both in vitro and in vivo models, to provide a relevant neuroprotective effect by its specific anti- amyloid activity and by its ψ-aminobutyric acid type A receptor affinity. The therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effects. In this review, we will examine the pre-clinical and clinical evidence supporting the potential role of homotaurine as a promising candidate for both primary and secondary prevention of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Marengoni A, Rizzuto D, Wang HX, Winblad B, Fratiglioni L. Patterns of chronic multimorbidity in the elderly population. J Am Geriatr Soc 2009; 57: 225–30.

    Article  PubMed  Google Scholar 

  2. Alzheimer’s Association. 2009 Alzheimer’s disease facts and figures. Alzheimers Dement 2009; 5: 234–70.

    Article  Google Scholar 

  3. Sperling RA, Aisen PS, Beckett LA et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 280–92.

    Article  PubMed  Google Scholar 

  4. Mura T, Dartigues JF, Berr C. How many dementia cases in France and Europe? Alternative projections and scenarios 2010–2050. Eur J Neurol 2010; 17: 252–9.

    Article  PubMed  CAS  Google Scholar 

  5. Dubois B, Feldman HH, Jacova C et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010; 9: 1118–27.

    Article  PubMed  Google Scholar 

  6. Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet 2006; 368: 387–403.

    Article  PubMed  CAS  Google Scholar 

  7. Gamblin TC, Chen F, Zambrano A et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc Natl Acad Sci U S A 2003; 100: 10032–7.

    Article  PubMed  CAS  Google Scholar 

  8. Rojo LE, Fernández JA, Maccioni AA, Jimenez JM, Maccioni RB. Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch Med Res 2008; 39: 1–16.

    Article  PubMed  CAS  Google Scholar 

  9. Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta peptide. Trends Mol Med 2001; 7: 548–54.

    Article  PubMed  CAS  Google Scholar 

  10. Weiner HL, Frenkel D. Immunology and immunotherapy of Alzheimer’s disease. Nat Rev Immunol 2006; 6: 404–16.

    Article  PubMed  CAS  Google Scholar 

  11. Ito K, Miyazawa K, Matsumoto F. Amino acid composition of the ethanolic extractives from 31 species of marine red algae. Hiroshima Daigaku Suichikusangakubu Kiyo 1977; 16: 77–90.

    CAS  Google Scholar 

  12. Miyazawa K, Ito K, Matsumoto F. Occurrence of (?)-2-hydroxy- 3-aminopropanesulfonic acid and 3-aminopropanesulfonic acid in a red alga, Grateloupia livida. Nippon Suisan Gakkaishi 1970; 36: 109–14.

    Article  CAS  Google Scholar 

  13. Wright TM. Tramiprosate. Drugs Today (Barc) 2006; 42: 291–8.

    Article  CAS  Google Scholar 

  14. Good NE, Winget GD, Winter W, Connolly TN, Izawa S, Singh RM. Hydrogen ion buffers for biological research. Biochemistry 1966; 5: 467–77.

    Article  PubMed  CAS  Google Scholar 

  15. Biasetti M, Dawson R Jr. Effects of sulfur containing amino acids on iron and nitric oxide stimulated catecholamine oxidation. Amino Acids 2002; 22: 351–68.

    Article  PubMed  CAS  Google Scholar 

  16. Messina SA, Dawson R Jr. Attenuation of oxidative damage to DNA by taurine and taurine analogs. Adv Exp Med Biol 2000; 483: 355–67.

    Article  PubMed  CAS  Google Scholar 

  17. Adembri G, Bartolini A, Bartolini R, Giotti A, Zilletti L. Proceedings: Anticonvulsive action of homotaurine and taurine. Br J Pharmacol 1974; 52: 439P–40P.

    PubMed  CAS  Google Scholar 

  18. Fariello RG, Golden GT, Pisa M. Homotaurine (3 aminopropanesulfonic acid; 3APS) protects from the convulsant and cytotoxic effect of systemically administered kainic acid. Neurology 1982; 32: 241–5.

    Article  PubMed  CAS  Google Scholar 

  19. Ruiz de Valderas RM, Serrano MI, Serrano JS, Fernandez A. Effect of homotaurine in experimental analgesia tests. Gen Pharmacol 1991; 22: 717–21.

    Article  PubMed  CAS  Google Scholar 

  20. Serrano MI, Serrano JS, Asadi I, Fernández A, Serrano-Martino MC. Role of K+-channels in homotaurine-induced analgesia. Fundam Clin Pharmacol 2001; 15: 167–73.

    Article  PubMed  CAS  Google Scholar 

  21. Scott LJ, Figgitt DP, Keam SJ, Waugh J. Acamprosate: a review of its use in the maintenance of abstinence in patients with alcohol dependence. CNS Drugs 2005; 19: 445–64.

    Article  PubMed  CAS  Google Scholar 

  22. Giotti A. Effect of homotaurine on the learning and maintenance of the conditioned reflex of escape in the rat. Boll Soc Ital Biol Sper 1975; 51: 1723–6.

    PubMed  CAS  Google Scholar 

  23. Liljequist R, Paasonen MK, Solatunturi E, Halmekoski J. Comparison of guanidinoethanesulfonic acid, homotaurine and beta- alanine in a learning situation. Acta Pharmacol Toxicol (Copenh) 1983; 52: 158–60.

    Article  CAS  Google Scholar 

  24. Santa-María I, Hernández F, Moreno FJ, Avila J. Taurine, an inducer for tau polymerization and a weak inhibitor for amyloid-beta- peptide aggregation. Neurosci Lett 2007; 429: 91–4.

    Article  PubMed  Google Scholar 

  25. Martineau E, de Guzman JM, Rodionova L, Kong X, Mayer PM, Aman AM. Investigation of the noncovalent interactions between anti-amyloid agents and amyloid beta peptides by ESI-MS. J Am Soc Mass Spectrom 2010; 21: 1506–14.

    Article  PubMed  CAS  Google Scholar 

  26. Krzywkowski P, Sebastiani G, Williams S. Tramiprosate prevents amyloid beta-induced inhibition of long-term potentiation in rat hippocampal slices. 8th International Conference AD/PD, Salzburg, Austria, March 14–18, 2007.

    Google Scholar 

  27. Azzi M, Morissette C, Fallon L. Involvement of both GABA-dependent and -independent pathways in tramiprosate neuroprotective effects against amyloid-beta toxicity. 8th International Conference AD/PD, Salzburg, Austria, March 14–18, 2007.

    Google Scholar 

  28. Gervais F, Paquette J, Morissette C, et al. Targeting Aβ peptide with tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 2007; 28: 537–47.

    Article  PubMed  CAS  Google Scholar 

  29. Aisen PS, Saumier D, Briand R et al. A Phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology 2006; 67: 1757–63.

    Article  PubMed  CAS  Google Scholar 

  30. Fulga TA, Elson-Schwab I, Khurana V et al. Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat Cell Biol 2007; 9: 139–48.

    Article  PubMed  CAS  Google Scholar 

  31. Greenberg SM, Rosand J, Schneider AT et al. A phase 2 study of tramiprosate for cerebral amyloid angiopathy. Alzheimer Dis Assoc Disord 2006; 20: 269–74.

    Article  PubMed  CAS  Google Scholar 

  32. Saumier D, Aisen PS, Gauthier S et al. Lessons learned in the use of volumetric MRI in therapeutic trials in Alzheimer’s disease: the ALZHEMED (tramiprosate) experience. J Nutr Health Aging 2009; 13: 370–2.

    Article  PubMed  CAS  Google Scholar 

  33. Aisen PS, Gauthier S, Ferris SH et al. Tramiprosate in mild-tomoderate Alzheimer’s disease — a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci 2011; 1: 102–11.

    Article  Google Scholar 

  34. Saumier D, Duong A, Haine D, Garceau D, Sampalis J. Domainspecific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer’s disease: ADAS-cog subscale results from the Alphase Study. J Nutr Health Aging 2009; 13: 808–12.

    Article  PubMed  CAS  Google Scholar 

  35. Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord 2005; 19: 163–5.

    Article  PubMed  Google Scholar 

  36. Sperling RA, Laviolette PS, O’Keefe K, O’Brien J, Rentz DM, Pihlajamaki M. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 2009; 63: 178–88.

    Article  PubMed  CAS  Google Scholar 

  37. Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN. The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex 2009; 19: 497–510.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Niccolò Marchionni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caltagirone, C., Ferrannini, L., Marchionni, N. et al. The potential protective effect of tramiprosate (homotaurine) against Alzheimer’s disease: a review. Aging Clin Exp Res 24, 580–587 (2012). https://doi.org/10.3275/8585

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3275/8585

Key words

Navigation