ANAVEX Advances Drug Candidates For Epilepsy Treatment
Anavex LifeSciences announced promising developments with ANAVEX 2-73 and ANAVEX 19-144,the company's lead drug candidates to treat epilepsy.
Duringrecent pre-clinical animal studies, ANAVEX 2-73 and ANAVEX 19-144 demonstratedsignificant anticonvulsant, anti-amnesic, neuroprotective and anti-depressantproperties.
Theseactivities involve muscarinic and sigma-1 receptor components, which issignificant because it indicates a novel mechanism of action. Pioneered byANAVEX, Sigma-1 receptors are a fairly new class of receptors -- moleculeswithin a cell or on a cell surface to which substances (drugs or hormones)selectively bind, causing a change in the activity of the cell.
"Currently,there are no drugs available that truly control epilepsy or preventepileptogenesis, a process that causes long-term tissue and cell damage as wellas biochemical and physiological alterations to the brain. These alterationscause seizures and are linked with the progressive deterioration or death ofthe body's nerve cells," said Dr. Kontzalis, Chief Executive Officer forANAVEX. "In addition, the drugs to treat epilepsy that are on the markettoday are often associated with cognitive, psychotic and memory problems. Assuch, we believe that novel drugs like ANAVEX 2-73 and ANAVEX 19-144, whichhave anti-epileptogenic, neuroprotective and anti-amnesic properties, arecertain to have a major impact on the anti-epileptic drug market around theworld."
Anticonvulsiveproperties were tested in epilepsy animal models with maximum electroshock(MES)- and pentylenetetrazole (PTZ)-induced generalized convulsions. In 90-100%of the treated animals versus the control group, both ANAVEX 2-73 and ANAVEX19-144 exhibited extremely significant anticonvulsive action by providingalmost complete protection from tonic seizures. This was accomplished withoutcausing any memory deficits (amnesic effect) or mood disturbances (depression).Memory deficits and depressive phenomena are usually observed with theanti-epileptic drugs available today.
InPTZ-induced convulsions it was further observed that ANAVEX 19-144 is able tosignificantly prolong life during a seizure. Control-group animals died afterthree minutes and two seconds, while animals that received ANAVEX 19-144 werestill alive after 50 minutes.
Thepre-clinical study tested the anti-amnesic properties of ANAVEX 2-73 and ANAVEX19-144 on mice, which were then submitted to short- and long-term memory tests,spontaneous alternation and passive avoidance respectively. Testing wasconducted in pharmacological and pathological mouse models of amnesia. When theepilepsy drug candidates were administered to the mice, the compound dosereversed the learning deficits induced by the drugs scopolamine and dizocilpineand by the administration of amyloid beta peptide. The effects of ANAVEX 2-73were linked to action at muscarinic and sigma-1 receptor sites because theywere blocked by pre-injection of the sigma-1 receptor antagonist BD 1047.
Theneuroprotective properties of ANAVEX 2-73 and ANAVEX 19-144 were studied in anon-transgenic mouse model of Alzheimer's disease. Central injection of amyloidbeta peptide in mouse brains is known to induce histological and biochemicalchanges, oxidative stress and learning deficits within seven days. ANAVEX 2-73or ANAVEX 19-144 administered once, either orally or by injection, preventedthe appearance of amyloid beta peptide-induced learning or memory deficits. Italso prevented oxidative stress, which damages and destroys cells, and nervecell loss in sensitive areas of the brain that regulate learning, emotion andmemory. In addition, the neuroprotective properties of ANAVEX 19-144 have beendemonstrated, in a transient focal cerebral ischemia mouse model, to reduce theinfarct area after ischemia by 28%.
Theneuroprotective properties of ANAVEX 2-73 and ANAVEX 19-144 have been observedat very low doses (0.1-0.3 mg/kg). These doses are far below the levels thatinduce cholinergic- or sigma 1 receptor-related side effects, verifying theanticipated enhanced safety profile of the ANAVEX epilepsy drug candidates.
"Weare confident that we have achieved proof-of-concept status for ANAVEX 2-73 andANAVEX 19-144," said Dr. Vamvakides, Chief Scientific Officer of ANAVEX."These latest results provide strong evidence as to the promise andpotential of our epilepsy drug candidates, which have anti-epileptogenic actionas well as an optimal efficacy and safety profile."
Ongoingpre-clinical studies, which are being conducted in collaboration withUniversite Montpellier in