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New Classes of Acetylcholinesterase Inhibitor: Natural Product Treatments for Alzheimer’s Disease
Collaborator and chief investigator: Professor Mary Garson
Alzheimer’s disease (AD) is the most common neurodegenerative disorder and is estimated to account for two thirds of dementia cases in persons over the age of 65 years. Acetylcholinesterase (AChE) inhibitors have beneficial effects on cognitive, functional, and behavioural symptoms of AD, and the American Academy of Neurology has recommended AChE inhibitors as “the first-line treatment in patients with mild to moderate AD”. Studies have also demonstrated the efficacy of AChE inhibitors in severe AD. Each year dementia costs the Australian economy billions of dollars in direct and indirect health care costs. One of the most important outcomes of improving the management of AD will be a reduction in health care expenditure.
Many AChE inhibitors used clinically for the treatment of AD are natural products or natural product analogues, such as rivastigmine (a physostigmine derivative), galantamine and huperzine A (available in China; in phase II trials in the USA). The only approved natural agents for the treatment of AD are alkaloids, which along with many of the synthetic AChE inhibitors (e.g. donepezil and tacrine) possess side-effects including nausea, vomiting, diarrhoea, and loss of appetite. In fact, tacrine was discontinued due to its significant side effect profile. There is considerable interest therefore in the discovery of more centrally selective non-alkaloidal inhibitors which may avoid the side effects that have been recorded with alkaloids. These natural products could also provide templates for the development of other compounds.
The aim of this study is to investigate terrestrial sources of natural products, particularly plants, for AChE inhibitors. Alkaloids will be examined, however a focus of the study will be non-alkaloidal natural products such as terpenoids, xanthones and coumarins. The discovery of a new class of potent and centrally selective AChE inhibitors with minimal side-effects would help treat AD; one of the most disabling and burdensome health conditions worldwide.
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Latest News
10 April 2008 , New PhD student: Mr Manoj Kumar Palanivelu started his PhD today, funded by a prestigious Australian Government Endeavour Postgraduate Award. Manoj will focus on the design, synthesis and in vitro evaluation of inhibitors of amyloid aggregation.
25 January 2008, New PhD student: Welcome Mr Venkatesan Moorthy Rao who commenced his PhD today. Venky will develop prodrug strategies for the CNS delivery of inhibitors of beta-amyloid aggregation. Previously Venky was a Lecturer at the School of Pharmacy, International Medical University in KL, Malaysia.
18 October 2007, New Funding: A grant from the Clive and Vera Ramaciotti Foundations will support our research into Novel Anti-Amyloidogenic Therapies for Alzheimer's Disease.
3 October 2007, Honours and PhD applicants: Students who are considering Honours or PhD projects for 2008 should meet with Dr Ross to discuss their options.
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Contact
Dr Ben Ross School of Pharmacy The University of Queensland Brisbane, Queensland, 4072 AUSTRALIA
Phone: +61 7 336 58808 Fax: +61 7 336 51688
Email:
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This web site was last updated on 12 April 2008. Copyright © 2006-2008 Benjamin P. Ross. Unless stated otherwise, this web site represents only the views of Benjamin P. Ross and not the views of The University of Queensland. Simple site map. |
