The ongoing 2022 Alzheimer's Association International Conference (AAIC) in San Diego has delivered a string of positive news for the AD space. We take a look at updates from Vivoryon, Anavex and Argentinian scientists below.
Vivoryon Posts Promising Preclinical Evidence Of A Potential AD Drug
Vivoryon shared two sets of preclinical data showcasing its N3pE amyloid-targeting therapeutic strategy's potential in mono- and combination therapy for Alzheimer's disease. N3pE amyloid (pGlu3-Abeta) is a toxic type of Abeta that hastens plaque aggregation and seeding, thus making it an important therapeutic target. N3pE amyloid that has formed can be catalyzed by QPCT, an enzyme expressed mainly by the learning and memory centers of the brain. Toxic N3pE is not found in healthy individuals.
The company's first preclinical report (Poster P1-457) showed that combining the QPCT/L inhibitor varoglutamstat and the N3pE amyloid-specific PBD-C06 can help lower N3pE amyloid in vivo.
Vivoryon evaluated whether a similar additive effect can be achieved if varoglutamstat is combined with Abeta-plaque-specific antibody aducanumab in a double transgenic mouse model that over expresses a variant of the human amyloid precursor protein and human QPCT. The animals were then given either varoglutamstat, chimeric aducanumab (chAdu) or a combination of both for 16 weeks and analyzed for accumulation markers.
The scientists found that single agent treatment with either varoglutamstat or chAdu reduced N3pE and total Abeta accumulation in the brain. The effect for chAdu also appeared to be greater on total Abeta, while varoglutamstat led to a stronger drop in N3pE amyloid levels.
In its second report (Poster P1-04), they explored the effect of 07/2a-k compared to 3D6-L in mice with AD. 3D6-L is a murine analog of bapineuzumab, a classical anti-Abeta antibody, while 07/2a-k is a CDC-mutant version of the PBD-C06 precursor 07/2a.
Results from the study on mice showed that 07/2a-k had no effect on the biochemical or pathological Abeta measures, but it modestly improved memory based on the Novel Object Recognition task. It did not have any impact when the Barnes maze metric was used. The good thing is that 07/2a-k did not result in any micro- or macro hemorrhages, whereas 3D6-L induced a high number.
Vivoryon is working on more preclinical trials to further assess the potential of PBD-C06.
Anavex Shares First Complete Gene Pathway Data on Parkinson's Disease Dementia Study
Anavex Life Sciences announced the first entire clinical gene pathway data from the Anavex 2-73-PDD-001 Parkinson's Disease Dementia PDD study. The randomized, placebo-controlled trial involved 132 PDD patients whose gene expressions were observed after 14 weeks. Pathway analysis showed the biological relevance of the PDD gene network and confirmed the effect of Anavex 2-73 on neurodegenerative illnesses, particularly PD and AD.
"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," Dr. Jaime Kulisevsky, M.D., Ph.D., the study's principal investigator said.
"PDD is a debilitating disorder with significant co-morbidities and 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," Kulisevsky added.
Trial participants had the option to enroll in a voluntary 48-week open-label extension trial after completing Anavex 2-73-PDD-001. This study is ongoing.
Argentinian Scientist Says Loss Of Smell From COVID-19 May Predict Disease Severity
A group of scientists from Argentina found that persistent loss of the sense of smell related to COVID-19 may be a better indicator of the disease's severity and long-term effect in initial cases.
Working with the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 Infection, the scientists observed 766 adults ages 55 to 95 years who were exposed to COVID-19 for a year. After a series of physical, cognitive and neuropsychiatric tests were conducted, the researchers found that two-thirds of the participants showed functional memory impairment.
Other metrics used showed similar outcomes, with 11.7% demonstrating memory-only impairment, 8.3% exhibiting attention and executive function impairment and 11.6% displaying multi-domain impairment. Of them all, persistent loss of smell was a common factor, especially in cognitive impairment.
"The more insight we have into what causes or at least predicts who will experience the significant long-term cognitive impact of COVID-19 infection, the better we can track it and begin to develop methods to prevent it," Gabriela Gonzalez-Aleman, LCP, Ph.D., a professor at Pontificia Universidad Catolica Argentina, Buenos Aires, commented.
Other notable findings that the scientists shared were the increased likelihood that intensive care unit stays will increase dementia risk and that introducing a positive life change amidst the pandemic may protect against symptoms of cognitive decline.
"This study is an example of how investigators from diverse countries in Latin America and the United States, many of whom had never worked together before and had limited resources, came together under difficult circumstances but with a shared goal to advance scientific understanding about Alzheimer's, and the important contributions that such multicultural partnerships can yield," María Marquine, Ph.D., associate professor in the Departments of Medicine and Psychiatry and director of disparities research in the Division of Geriatrics, Gerontology and Palliative Care at the University of California, San Diego, noted.
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