Anavex 2-73, an investigational therapy being evaluated in clinical trials for Alzheimer’s disease, was found to restore the function of damaged nerve cells in mouse models of Parkinson’s disease.
Based on the favorable safety profile seen in the clinic, the findings support the hypothesis that Anavex 2-73 might be a promising approach for treating Parkinson’s disease patients.
The preclinical findings were presented at the Michael J. Fox Foundation’s Parkinson’s Disease Therapeutics Conference, held Oct. 30 in New York City. The poster was titled, “ANAVEX 2-73, a clinical Alzheimer drug candidate, induces neurorestoration in experimental parkinsonism.”
Veronica Francardo, PhD, and Dr. Angela Cenci, an MD and PhD, from Lund University in Sweden, the study’s principal investigators, said in a press release that the encouraging results that were gathered in this mouse model, “coupled with the favorable profile of this compound in the Alzheimer’s disease trial, support the notion that Anavex 2-73 is a promising clinical candidate drug for Parkinson’s disease.”
Anavex Life Sciences has been developing Anavex 2-73 as a disease-modifying drug for Alzheimer’s disease. It is an orally available, small molecule that activates the sigma-1 receptor, which is involved in several cellular regulatory mechanisms.
The drug candidate has the potential to restore the molecular balance of cells by targeting misfolded proteins and mitochondria dysfunction. This ultimately prevents oxidative stress, inflammation, and cellular stress, processes that are shared by many neurological disorders and known to contribute for nerve cell degeneration.
One of the major features in Parkinson’s disease is the loss of brain nerve cells in the substantia nigra, a brain region that controls movement. Loss of neurons in this region leads to a reduction in dopamine – a neurotransmitter essential for neuronal communication. As a result, progressive degeneration of neurons in the substantia nigra is linked to the severity of Parkinson’s motor deficits.
Researchers at Lund University, in collaboration with Anavex, had already shown that Anavex 2-73 significantly improved motor function in mice with Parkinson’s-like disease. In particular, the treatment was found to restore the structure of brain nerve fibers while reducing the activity of brain immune cells.
More recent data provided further insight: Anavex 2-73 activates a series of brain restructuring processes that ultimately restore nerve fibers in the substantia nigra of the Parkinson’s mice. This was further confirmed with a maker of cell growth – the growth associated protein 43 (GAP43) – which was only present in the brains of treated mice, and not on untreated animals.
“These findings are very encouraging and support our strategy to initiate a randomized and placebo-controlled Phase 2 study in Parkinson’s disease with ANAVEX 2-73,” said Christopher U. Missling, PhD, president and CEO of Anavex.
The research team is conducting additional studies to better understand the underlying mechanism of Anavex 2-73’s neurorestorative activity.
This study was supported by The Michael J. Fox Foundation for Parkinson’s Research.
Anavex 2-73 is being evaluated in a Phase 2 trial (NCT02244541) in patients with Alzheimer’s disease. The company is planning to initiate a Phase 2/3 trial that will enroll up to 300 patients with mild-to-moderate Alzheimer’s disease.
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