The first entire clinical gene pathway data from the ANAVEX2-73-PDD-001 Parkinson’s Disease Dementia (PDD) study was released at the Alzheimer’s Association International Conference (AAIC) in San Diego.
The randomized, placebo-controlled clinical trial in 132 patients with Parkinson’s disease dementia (PDD) included prespecified biomarkers of response as well as Whole Exome Sequencing DNA data and full RNA exome expression data collection.
While genes are known to be down-regulated in Alzheimer’s disease and Parkinson’s disease, representing pathology for these diseases, ANAVEX2-73 singularly impacted expression levels of these genes in multiple pathways by countering the pathological down-regulation of genes in both Alzheimer’s and Parkinson’s disease and other degenerative diseases.
The scope of these detected gene expressions identified through ANAVEX2-73 effect may represent additional potential biomarkers of disease pathology and response.
ANAVEX2-73 transcriptomics analysis (RNAseq) identified a gene network that is differentially expressed in Parkinson’s disease dementia (PDD) patients treated with ANAVEX2-73 compared to placebo after 14 weeks of treatment. The expression of 14,150 genes were analyzed from both placebo and drug treated patients.
The poster presentation (abstract #59024): “Study of the mechanism of action of Blarcamesine (ANAVEX®2-73): Whole blood transcriptomics analysis (RNAseq) identifies treatment impact on compensatory pathways by restoring key neurodegenerative pathways functionality, including Alzheimer’s and Parkinson’s disease pathways” was givenby the principal author, Mohammad Afshar, MD, PhD, Ariana Pharma, Paris, France and Cambridge, US.
Previously, this study demonstrated dose-dependent, statistically significant improvement of dementia assessment, Quality of Episodic Memory with ANAVEX2-73, as well as significant improvement of Parkinson’s assessment, MDS-UPDRS Total score, in patients treated with the drug high oral dose once daily during the 14-week trial.
SIGMAR1 mRNA expression significantly increased in ANAVEX2-73-treated patients vs placebo (p=0.035) over the course of treatment and was significantly associated with improvements of MDS-UPDRS scores and cognitive efficacy endpoints CDR system.
Jaime Kulisevsky, MD, PhD, Principal Investigator of the trial, commented, “To my knowledge, this represents the first extensive transcriptomics analysis (RNAseq) of a therapeutic agent in patients with Parkinson’s disease dementia (PDD).
“It is very intriguing to confirm this robust correlation of the clinical improvements of motor impairment (MDS-UPDRS) and cognition (CDR system) with compensation of expression levels of dysregulated neurodegenerative genes, especially Alzheimer’s disease and Parkinson’s disease, through the therapeutic effect of ANAVEX®2-73. PDD is a debilitating disorder with significant co-morbidities
He noted that “There has not been a mechanistically novel medication approved for PDD in over 20 years. Hence, new therapies are urgently needed to alleviate this suffering and disability.”