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Neurorestorative Effects of a Sigma-1 Receptor Agonist in a Model of Parkinson’s Disease

Study Rationale:                   
In a previous MJFF-sponsored project, we evaluated PRE-084 (an experimental compound binding to the sigma-1 receptor) in pre-clinical models of Parkinson’s disease. Chronic treatment with PRE-084 produced a gradual improvement of motor deficits and activated molecules involved in brain repair. In this project, we will evaluate a sigma-1 receptor agonist (ANAVEX2-73) produced by Anavex, which is now being evaluated in patients with Alzheimer’s disease. In our experimental study, the efficacy of ANAVEX2-73 on Parkinson’s biology will be compared to that of PRE-084 and other Sig-1R ligands.

The overarching aims of the study are to find a dose of ANAVEX2-73 producing a pattern of neurorestorative effects comparable to that of PRE-084 and to translate this dose into an equivalent dose for human use.

Study Design:
We will test the biological activity of ANAVEX2-73 in pre-clinical models and compare to PRE-084, previously shown to promote recovery of forelimb use, up-regulation of trophic factors and anti-inflammatory effects in the brain in this model. We will assess target engagement by measuring the ability of the tested compounds to prevent a radioactive ligand from binding to brain sigma-1 receptors.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
The present study holds potential to impact the way Parkinson’s disease is treated. We aim to develop a new pharmacological approach to boost repair mechanisms and dampen inflammation in the part of the brain that is most affected by Parkinson’s. If this treatment exerts the expected effects, it could slow the progression of the disease.

Next Steps for Development:
If successful, this study will accelerate the translation of pre-clinical findings into the first clinical trial of ANAVEX2-73 as a potential disease-modifying therapy for Parkinson’s disease. ANAVEX2-73 has already been tested for safety and tolerability in humans with positive results.


  • M. Angela Cenci Nilsson, MD, PhD

    Lund Sweden

  • Christopher U. Missling, PhD, MBA

    New York, NY United States

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