Page 85 in abstract
P11.04
Investigating the potential neurorestorative effects of a clinical
Sigma-1 receptor agonist in a mouse model of Parkinson’s
disease.
Veronica Francardo1
, Francesco Bez1
, Jeffrey Sprouse2
,
Christopher Missling2
, M. Angela Cenci Nilsson1
1
Basal Ganglia Pathophysiology Unit, Department of Experimental
Medical Science, Lund University, Lund, Sweden
2
Anavex Life Sciences, New York, New York, USA
Background: Sigma-1 receptor is an endoplasmic reticulum-
chaperone protein promoting mechanisms that protect cells under
stress. We have recently demonstrated, for the first time in an
animal model of Parkinson’s disease (PD), that a compound known
to enhance the activity of Sig-1R promotes recovery of motor
functions and activates neuroplasticity mechanisms in the
nigrostriatal system (Francardo et al Brain 2014).
Objective: Using the same animal model of PD as in our previous
study, we aim to investigate the potential neurorestorative effects of
ANAVEX 2-73, a compound with activity at both Sigma-1 and
muscarinic receptors that is currently being tested in people affected
by Alzheimer’s disease. In addition, we aim to study the Sigma-1
receptor occupancy of different doses of ANAVEX 2-73 in the brain.
Methods: The following experiments are now ongoing: (i) dose-
response effects of ANAVEX 2-73 on the behavior of intact mice, (ii)
setting up a radiographic method to assess brain Sigma-1 receptor
occupancy by ANAVEX 2-73 in the mouse, (iii) behavioral-
pharmacological evaluation of the effects of the compound in mice
sustaining intrastriatal 6-hydroxydopamine (6-OHDA) lesions.
Treatment is given daily for 5 weeks.
Results: In intact mice, ANAVEX 2-73 reduced novelty/stress-
induced horizontal activity (a potential anxiolytic effect), although
basal activity levels were not significantly reduced. Behavioral
patterns were completely normal (no signs of either dystonia or
stereotypic behaviors). Ongoing experiments on mice sustaining 6-
OHDA lesions show trends towards an amelioration of parkinsonian
motor symptoms in tests assessing spontaneous rotational activity
and forelimb use asymmetry.
Significance: If successful, this study will accelerate the clinical
development of ANAVEX 2-73 as a potential disease-modifying
therapy for PD. We are in the fortunate situation that safety,
bioavailability, tolerability of this compound have already been
proven in human subjects, and that preliminary indications of a
cognitive benefit have been obtained in a Phase 2a clinical trial for
Alzheimer’s disease (ANAVEXTM Life Science Corp).
P11.06
Laughter benefits – what would Robin Williams sa
