Anavex Life Sciences has reported promising results from animal studies with Anavex 2-73, the company's lead compound for the treatment and modification of Alzheimer's disease.
Anavex 2-73 is the first of a new class of drugs that target mitochondrial dysfunction thought to be caused by oxidative stress to modify Alzheimer's disease.
This novel mechanism acts primarily via sigma receptors and is not a direct amyloid, nor tau, nor mitochondrial pore blockage mechanism.
Anavex is developing non-amyloid focused approaches to disease modification in modification in Alzheimer's disease and believes mitochondrial dysfunction caused by oxidative stress to be an underlying cause of Alzheimer's disease.
By modulating ion channel signalling at a mitochondrial level, the company believes this class of patent-pending compounds may offer a new disease-modifying approach in several neurological and neurodegenerative disorders.
Validated and standard animal models used to assess effects typically seen in Alzheimer's disease have been completed with good results.
These studies were conducted in partnership with a contact research organisation Forenap Pharma Eurl, which specialises in neuroscience and Alzheimer's disease research.
The studies included oral and IV dosing and 28-day animal toxicity studies.
Extensive studies were conducted in three separate species: rats, mice and dogs.
The company expects to submit the IND (investigational new drug) package to regulatory authorities in the near term.
Dr Cameron Durrant, executive chairman of Anavex, said: 'The highly selective binding properties of Anavex 2-73 has led to beneficial effects at very low doses, which many ultimately lead to a favourable tolerability profile and offer a wide therapeutic index.
'This may mean many patients could benefit from low doses, although going to higher doses may be possible in some patients to offer greater efficacy without compromising on the tolerability profile.
'Anavex is confident in the emerging profile of Anavex 2-71 as it prepares for Phase 1 clinical trials.
'We have established that sigma receptors are druggable targets and we have worked to shape Anavex 2-73 as our optimised lead compound, which may prove to be neuroprotective,' Durrant added.
When administered prior to amyloid-beta 25-35 peptide, Anavex 2-73 protected against the amyloid peptide-induced learning deficits, hippocampal lipid peroxidation and cell loss in the CA1 pyramidal layer and showed potent neuroprotective activity.
Extensive in-vitro receptor binding and electrophysiology studies, sigma receptor binding studies and electrophysiological effects on sodium and calcium currents have been completed.
The binding affinities of Anavex 2-73 for more than 50 receptors were studied.
The potency of Anavex 2-73, inhibiting enzyme activities was also studied on enzyme assays including calpain, nitric oxide synthase (constructive and inducible form), protein kinase (PKCa and PKCss), EGF receptor kinase and calcineurin.
Durrant said: 'Anavex 2-73 is a novel oral disease modification agent that is believed to act at several levels, including the mitochondria, and may offer a therapy that could be used as a standalone or in combination with other agents if development proves successful.
'Currently available therapies primarily treat the symptoms, as opposed to modifying the disease, and can fade in terms of effectiveness over time.
'Several experimental therapies being developed will have to be administered as injections or intravenous infusions.
'Anavex 2-73, and the follow-on compounds the company has in its pipeline, may prove to be novel disease-modifying agents that could impact the natural history of Alzheimer's disease, and which may be administered orally.'