Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-29T08:20:58.951Z Has data issue: false hasContentIssue false

Amyloid-Based Therapeutics: Findings Translated into Novel Treatments

Published online by Cambridge University Press:  07 November 2014

Paul S. Aisen*
Affiliation:
Dr. Aisen is director of the Alzheimer’s Disease Cooperative Study, and Professor of Neurosciences at the, University of California, at San Diego

Extract

For decades following the 1906 identification of Alzheimer’s disease (AD), it was believed that the disorder was untreatable. Only in the late 1970s, with the introduction of the cholinergic hypothesis of the underlying mechanisms of AD, were treatment options considered possible. The first positive treatment study was conducted in 1985. In 1993, tacrine, a cholinesterase inhibitor, was approved for the treatment of AD; three similar drugs soon followed. Memantine, an NMDA receptor antagonist, was approved in 2003, representing a second therapeutic class for AD.

Cholinesterase inhibitors were the first therapeutic options successfully employed, and there is strong evidence these agents confer benefits. The addition of memantine to the standard course of therapy can be beneficial as well, particularly at the moderate stages of the disorder (Mini-Mental State Exam score of ≤14). For patients without cardiovascular disease, diabetes, or statin use, 1,000 IU vitamin E BID is a consideration to mitigate the effects of AD. However, there is presently concern over the risks involved in vitamin E therapy. Unfortunately, there are no established treatments for mild cognitive impairment (MCI). Vitamin E is ineffective in treating MCI, and cholinesterase inhibitors, while possibly risky, are only minimally effective. The need for effective treatment remains expansive. The benefits of the available agents are modest, and there are currently no treatments for individuals with memory impairment who do not yet meet the diagnostic criteria for AD.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Summers, WK, Majovski, LV, Marsh, GM, Tachiki, K, Kling, A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, alzheimer type. N Engl J Med. 1986;315:12411245.CrossRefGoogle ScholarPubMed
2.Cummings, JL. Alzheimer’s disease. N Engl J Med. 2004;351:5667CrossRefGoogle ScholarPubMed
3.Miller, ER 3rd, Pastor-Barriuso, R, Dalal, D, Riemersma, RA, Appel, LJ, Guallar, E. Meta-analysis: High-dosage vitamin e supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:3746.CrossRefGoogle ScholarPubMed
4.Lonn, E, Bosch, J, Yusuf, S, et al.Effects of long-term vitamin e supplementation on cardiovascular events and cancer: A randomized controlled trial. JAMA. 2005;293:13381347.Google Scholar
5.Petersen, RC, Thomas, RG, Grundman, M, et al.Vitamin e and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):23792388.Google Scholar
6.Aisen, PS. Treatment for mci: Is the evidence sufficient? Neurology. 2008;70:20202021.Google Scholar
7.Aisen, PS. The development of anti-amyloid therapy for alzheimer’s disease: From secretase modulators to polymerisation inhibitors. CNS Drugs. 2005;19:989996CrossRefGoogle ScholarPubMed
8.Hardy, J, Selkoe, DJ. The amyloid hypothesis of alzheimer’s disease: Progress and problems on the road to therapeutics. Science. 2002;297:353356.Google Scholar
9.Fox, NC, Black, RS, Gilman, S, et al.Effects of abeta immunization (an1792) on mri measures of cerebral volume in alzheimer disease. Neurology. 2005;64:15631572.Google Scholar
10.Gilman, S, Koller, M, Black, RS, et al.Clinical effects of abeta immunization (an1792) in patients with ad in an interrupted trial. Neurology. 2005;64:15531562.Google Scholar
11.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;67:17571763Google Scholar
12.McLaurin, J, Kierstead, ME, Brown, ME, et al.Cyclohexanehexol inhibitors of abeta aggregation prevent and reverse alzheimer phenotype in a mouse model. Nat Med. 2006;12:801808.Google Scholar
13.Sano, M, Ernesto, C, Thomas, RG, et al.A controlled trial of selegiline, alpha-tocopherol, or both as treatment for alzheimer’s disease. N Engl J Med. 1997;336:12161222.CrossRefGoogle ScholarPubMed
14.Tuszynski, MH, Thal, L, Pay, M, et al.A phase 1 clinical trial of nerve growth factor gene therapy for alzheimer disease. Nat Med. 2005;11:551555.Google Scholar
15.Matsuoka, Y, Jouroukhin, Y, Gray, AJ, et al.A neuronal microtubule-interacting agent, napvsipq, reduces tau pathology and enhances cognitive function in a mouse model of alzheimer’s disease. J Pharmacol Exp Ther. 2008;325:146153.Google Scholar