阿茲海默症的新救星？淺談Homotaurine (高牛磺酸)

 

攝影師：Alina Vilchenko: https://www.pexels.com/zh-tw/photo/10505442/

 

    高牛磺酸 (Homotaurine, 3-APS, Tramiprosate) 由一個氨基與丙烷磺酸構成，與牛磺酸僅只一個碳數之差，存在於天然海藻中。其結構與γ-胺基丁酸 (GABA) 相近，故亦具有抑制大腦神經的效果。近年發現該結構能夠抑制Aβ類澱粉蛋白的形成，因此被列為治療輕度阿茲海默症的候選藥物之一。

高牛磺酸結構

CAS Number: 3687-18-1

Molecular Weight: 139.17

 

Homotaurine能延緩阿茲海默症的病變

    隨著現代醫療的發達，人類的平均壽命逐漸提高，伴隨而來人口老化的健康問題亦將逐年升高。根據世界衛生組織 (WHO) 和國際失智症協會 (ADI) 的估計，預計到 2050年認知障礙的患病率將增加3倍，屆時全球將會有1.32億人受到影響^[1]。

    高牛磺酸除了在腦內具有抑制神經活動的活性以外，多則研究顯示，高牛磺酸也能延緩阿茲海默症的病變，以口服方式給藥，能穩定腦內Aβ40與Aβ42多肽單體，不至於聚集成類澱粉蛋白^[2-5]。其他研究也發現，患者在接受高牛磺酸治療之後，減緩其海馬迴萎縮的體積變化，這意味著具有延緩腦部萎縮的效果。^[6-8]

 

除了阿茲海默症之外 –在糖尿病的治療

    另有針對第一型糖尿病患者的相關研究，該研究指出在接受高牛磺酸治療之後，具有代謝症狀的小鼠體內的免疫系統能夠得到控制，進而改善胰島素的分泌，因此高牛磺酸也被視為治療第一型糖尿病的候選藥物。^[9]

Homotaurine與 ALZ-801

  ALZ-801屬於高牛磺酸的前體藥物，它是在高牛磺酸的氨基上修飾了一當量的纈胺酸官能基。ALZ-801在體內會代謝回高牛磺酸的結構，但藉由胺基酸的修飾可提升藥物活性，使藥物能夠更容易被人體吸收，在病患血液中維持更長的時間。目前已有多個對阿茲海默症的研究，甚至有進行到臨床三期的相關報導[10-12]。

 

ALZ-801結構

CAS Number:1034190-08-3

Molecular Weight:238.30

 

聚和的磺酸化工藝

    聚和擁有成熟的磺酸化修飾技術及純化設備，能提供高純度、高品質的胺基磺酸化合物，而這些產品被應用在醫藥、藥妝、能源和電鍍等相關產業。

Further reading:Sulfobutyl ether beta-cyclodextrin(SEβCD)之市場應用

了解更多關於 Hopax Homotaurine

 

 

參考資料
[1]World Alzheimer Report 2015 - The Global Impact of Dementia : An analysis of prevalence, incidence, cost and trends. / Prince, Martin James; Wimo, Anders; Guerchet, Maelenn Mari; Ali, Gemma Claire; Wu, Yu-Tzu; Prina, Matthew.London : Alzheimer's Disease International, 2015. 84 p.
[2]Gervais F, Paquette J, Morissette C, Krzywkowski P, Yu M, Azzi M, et al.. Targeting soluble Aβ peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. (2007) 28:537–47. 10.1016/j.neurobiolaging.2006.02.015
[3]Abushakra S, Porsteinsson A, Vellas B, Cummings J, Gauthier S, Hey JA, et al.. Clinical benefits of tramiprosate in Alzheimer's disease are associated with higher number of APOE4 alleles: the APOE4 gene-dose effect. J Prev Alzheimers Dis. (2016) 3:219–28. 10.14283/jpad.2016.115
[4]Kocis P, Tolar M, Yu J, Sinko W, Ray S, Blennow K, et al.. Elucidating the Aβ42 anti-aggregation mechanism of action of tramiprosate in Alzheimer's disease: integrating molecular analytical methods, pharmacokinetic and clinical Data. CNS Drugs. (2017) 31:495–509. 10.1007/s40263-017-0434-z
[5]Tolar M, Abushakra S, Sabbagh M. The path forward in Alzheimer's disease therapeutics: reevaluating the amyloid cascade hypothesis. Alzheimers Dement. (2019) 1–8. 10.1016/j.jalz.2019.09.075
[6]Gauthier S, Aisen PS, Ferris SH, Saumier D, Duong A, Haine D, et al.. Effect of tramiprosate in patients with mild-to-moderate Alzheimer's disease: exploratory analyses of the MRI sub-group of the Alphase study. J Nutr Heal Aging. (2009) 13:550–7. 10.1007/s12603-009-0106-x
[7]Saumier D, Aisen PS, Gauthier S, Vellas B, Ferris SH, Duong A, et al.. Lessons learned in the use of volumetric MRI in therapeutic trials in Alzheimer's disease: the ALZHEMEDTM (tramiprosate) experience. J Nutr Heal Aging. (2009) 13:370–2. 10.1007/s12603-009-0047-4
[8]Sabbagh MN. Clinical effects of oral tramiprosate in APOE4/4 homozygous patients with mild Alzheimer's disease suggest disease modification. J Prev Alzheimers Dis. (2017) 4:136–7. 10.14283/jpad.2017.24
[9]Tian J, Dang H, O'Laco KA, Song M, Tiu BC, Gilles S, Zakarian C, Kaufman DL. Homotaurine Treatment Enhances CD4+ and CD8+ Regulatory T Cell Responses and Synergizes with Low-Dose Anti-CD3 to Enhance Diabetes Remission in Type 1 Diabetic Mice. Immunohorizons. 2019 Oct 21;3(10):498-510. doi: 10.4049/immunohorizons.1900019.
[10]Tsolaki M. Future strategies of management of Alzheimer's Disease. The role of homotaurine Hell J Nucl Med. (2019) 22:82–94.
[11]Caltagirone C, Ferrannini L, Marchionni N, Nappi G, Scapagnini G, Trabucchi M. The potential protective effect of trampirosate (homotaurine) against Alzheimer's disease: a review. Aging Clin Exp Res. (2012) 24:580–7. doi: 10.3275/8585
[12]Abushakra S, Porsteinsson A, Scheltens P, Sadowsky C, Vellas B, Gauthier S, et al. Clinical effects of tramiprosate in APOE4/4 homozygous patients with mild Alzheimer's disease suggest disease modification potential. J Prev Alzheimers Dis. (2017) 4:149–56. doi: 10.14283/jpad.2017.26