Alzheimer's disease is the most common cause of dementia and is characterized by the progressive degeneration of cognition as a result of the destruction of nerve cells in the brain. Alzheimer's disease can result in the symptoms of memory loss, the alteration of an individual's personality and the failure to communicate or perform routine tasks.Associated with a dramatic deterioration in the quality of life of the sufferer, Alzheimer’s disease leaves the sufferer vulnerable to a number of co-morbidities such as depression, anxiety, sleeping disorders and also injury. The disease imposes significant socioeconomic and psychological burden on family members and caregivers that can be as dramatic as its impact on the patients suffering from it. At over $100 billion per year, AD is the third most costly disease in the U.S., after heart disease and cancer. Dementia affects an estimated 37 million people worldwide and about 50% of the cases are caused by AD. The U.S. Alzheimer's Association estimates that by 2025 over 22 million people will be affected around the world. The currently available drugs are insufficient to cure the disease but have some effect in treating the symptoms. Treatments that prevent onset of the disease (treat underlying cause of the disease) and/or slow/halt disease progression (reverse disease progress) are highly requested. The world AD market based on 2004 sales is US$2.7 billion and it is estimated to grow to US$6.5 billion by 2010 and US$10.6 billion by 2015.

ANAVEX 1-41
ANAVEX 1-41 is a new tetrahydrofuranic compound in advanced preclinical phase for the treatment of neurodegenerative diseases and especially Alzheimer disease. ANAVEX 1-41 presents a mixed pharmacological activity involving the modulation of muscarinic and sigma-1 components showing prominent anti-amnesic, antidepressant and weak anticonvulsant activity at low sigma-1 agonistic doses. In addition, ANAVEX 1-41 presents mixed pharmacological activity involving the modulation of sigma-1 receptors as well as sodium and chloride channels showing prominent neuroprotection mainly through the alleviation of amyloid-β induced oxidative stress and its anti-apoptotic properties. More specifically, the drug simultaneously acts as an agonist on postsynaptic M1 receptor and as an antagonist on presynaptic M2 autoreceptors. It also presents potent pro-amnesic or anti-amnesic properties by activating membrane-bound M1 receptors and intracellular sigma-1 receptors mainly located on the endoplasmic reticulum. Both receptors have been shown to activate phospholipase C (PLC) and protein kinase C (PKC)-dependent and mitogen-activated protein kinase (MAPK) pathways. Consequently, in Alzheimer Disease (AD) animal models ANAVEX 1-41 reversed the short and long term memory deficits, induced by scopolamine, dozocilpine (MK-801) or β25-35 amyloid, at very low doses, 17 to 1700 fold below the dose levels inducing unwanted secondary (cholinergic and other) effects. In vivo toxicology studies in healthy amimals indicate reduced or no adverse events combined with non addictive action since dopaminergic action has been excluded. Nevertheless, additional preclinical in vivo trials are currently being conducted to further assess and analyze the anti-amnesic and neuroprotective properties of ANAVEX 1-41 and related derivatives and develop drugs that will hopefully lead to disease-modifying therapies for this devastating disease. Positive preclinical results and toxicological data suggest the discovery and development of a product candidate for the treatment of AD with blockbuster potential. ANAVEX 1-41 has demonstrated neuroactivating (sigma/muscarinic) and neuroprotective (sigma/ion channels) potential in a synergistic and completely novel mode of action, complemented with antidepressant action, no addictive potential and few or no adverse events. Additional preclinical studies are currently underway to assess its preventive potential.