Alzheimer’s disease is a progressive degenerative brain disorder that destroys brain cells, causing memory loss and problems with thinking and behavior severe enough to affect work, lifestyles or social life. Alzheimer’s gets worse over time, and it is fatal.

Alzheimer’s disease is the most common dementia among older adults. As many as 5.3 million people in the United States are living with Alzheimer’s, with that number expected to grow to 14 million by 2050.

The worldwide prevalence of Alzheimer’s disease alone was over 26 million in 2006, as reported by Johns Hopkins University, and is expected to quadruple by 2050. According to IMS, annual sales for drugs that combat Alzheimer’s disease are projected to reach $8 billion by 2012.

No treatment is available to slow or stop the deterioration of brain cells in Alzheimer’s disease. The U.S. Food and Drug Administration has approved five drugs that temporarily slow the worsening effects of the symptoms for 6 to 12 months, on average, for about half of the individuals who take them. There remains a significant medical need in Alzheimer’s disease.

For an overview of Alzheimer’s disease, please click here.

ANAVEX is developing novel treatments that are currently undergoing late pre-clinical investigation.

ANAVEX 2-73
A novel sigma 1 receptor agonist targeting Alzheimer’s disease, preclinical trials completed

Mode of action: ANAVEX 2-73 has been shown to provide protection from oxidative stress, which damages and destroys neurons and is believed to be a primary cause of Alzheimer’s disease. Research in recent years indicates that oxidative stress is a precursor to amyloid-beta plaques and tau (Neuro-Fibrillary Tangles or NFT), and that protecting against oxidative stress may help to prevent or slow the disease. ANAVEX 2-73 may protect neurons from degeneration.

Results to date: During preclinical studies (in vitro and in vivo in mice), ANAVEX 2-73 demonstrated significant neuroprotective, anti-amnesic and anti-convulsive properties. It also exhibited an excellent safety profile and therapeutic activity at very low doses.

Moving forward: ANAVEX is engaging a Contract Research Organization to prepare the IND or IMPD submission for Phase I/IIa clinical trials, which are targeted to commence by September.

ANAVEX 1-41
A novel tetrahydrofuranic compound, now in the advanced preclinical phase, targeting Alzheimer’s disease

Mode of action: ANAVEX 1-41 presents a mixed pharmacological activity involving the modulation of sigma-1 and muscarinic components showing prominent anti-amnesic, anti-depressant and weak anti-convulsive activity at low sigma-1 agonistic doses. In addition, it presents mixed pharmacological activity involving the modulation of sigma-1 receptors as well as sodium and chloride channels showing neuroprotection.

Results to date: preclinical tests revealed significant neuroprotective benefits through the prevention of oxidative stress, which damages and destroys cells and is believed to be a primary cause of Alzheimer’s disease. In addition, ANAVEX 1-41 prevented the expression of caspase-3, an enzyme that plays a key role in apoptosis (programmed cell death) and in the loss of cells in the hippocampus, the part of the brain that regulates learning, emotion and memory. These activities involve both sigma-1 and muscarinic receptor systems through a novel mechanism of action.

Moving forward: ANAVEX is currently conducting additional preclinical in vivo trials in order to further study the anti-amnesic and neuroprotective properties of ANAVEX 1-41 and its related derivatives.