AAIC 2022: Vivoryan, Anavex and More Tout Innovation in the Alzheimer space


The Alzheimer’s Association International Conference (AAIC) underway in 2022 in San Diego has delivered a series of positive news for the AD space. Below we take a look at updates from Vivoryon, Anavex and Argentinian scientists.

Vivoryon releases promising preclinical evidence for potential AD drug

Vivoryon share two sets of preclinical data demonstrating the potential of its therapeutic strategy targeting amyloid N3pE as monotherapy and in combination in Alzheimer’s disease. Amyloid N3pE (pGlu3-Abeta) is a toxic type of Abeta that accelerates plaque aggregation and seeding, making it an important therapeutic target. The N3pE amyloid that is formed can be catalyzed by QPCT, an enzyme expressed primarily 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 the combination of varoglutamstat, a QPCT/L inhibitor, and amyloid N3pE-specific PBD-C06 can help reduce amyloid N3pE in vivo.

Vivoryon evaluated whether a similar additive effect can be obtained if varoglutamstat is combined with aducanumab, an Abeta plaque-specific antibody, in a double transgenic mouse model that overexpresses a variant of human amyloid precursor protein and human QPCT. Animals then received varoglutamstat, chimeric aducanumab (chAdu), or a combination of the two for 16 weeks and were analyzed for accumulation markers.

Scientists found that single-agent treatment with either varoglutamstat or chAdu reduced the accumulation of N3pE and total Abeta in the brain. The effect of chAdu also appeared to be greater on total Abeta, while varoglutamstat caused a greater drop in amyloid N3pE levels.

In their second report (Poster P1-04), they explored the effect of 07/2a-k versus 3D6-L in mice with AD. 3D6-L is a murine analog of the classical anti-Abeta antibody bapineuzumab, while 07/2a-k is a CDC mutant version of the PBD-C06 precursor 07/2a.

Results from the mouse study showed that 07/2a-k had no effect on biochemical or pathological Abeta measures, but slightly improved memory based on the novel object recognition task. . This had no impact when Barnes’ maze metric was used. The good thing is that 07/2a-k caused no micro or macro hemorrhages, whereas 3D6-L induced a high number.

Vivoryon is working on further preclinical trials to further evaluate the potential of PBD-C06.

Anavex shares first comprehensive genetic pathway data from Parkinson’s disease dementia study

Anavex life sciences announcement the first comprehensive clinical data on the genetic pathway from the Anavex 2-73-PDD-001 study in Parkinson’s disease and PDD dementia. The randomized, placebo-controlled trial involved 132 patients with PDD 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 diseases, especially PD and AD.

“To my knowledge, this is the first in-depth transcriptomic analysis (RNAseq) of a therapeutic agent in patients with Parkinson’s disease dementia (PDD). It is very exciting to confirm this robust correlation of clinical improvements motor impairment (MDS-UPDRS) and cognition (CDR system) with compensation of the expression levels of deregulated neurodegenerative genes, in particular Alzheimer’s disease and Parkinson’s disease, thanks to the therapeutic effect of ANAVEX 2-73,” Dr. Jaime Kulisevsky, MD, Ph.D., lead researcher of the study said.

“PDD is a debilitating disorder with significant comorbidities and there has not been a new mechanically approved drug for PDD in over 20 years. Therefore, new therapies are urgently needed to alleviate this suffering and disability,” Kulisevsky added.

Trial participants had the option of enrolling in a 48-week voluntary open-label extension trial after completing Anavex 2-73-PDD-001. This study is ongoing.

Argentinian scientist says loss of smell due to COVID-19 can predict disease severity

A group of Argentinian scientists found this persistent COVID-19-related loss of smell may be a better indicator of disease severity and its long-term effects in initial cases.

In collaboration with the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 Infection, scientists observed 766 adults aged 55 to 95 who were exposed to COVID-19 for one year. . After a series of physical, cognitive and neuropsychiatric tests, the researchers found that two-thirds of the participants had impaired functional memory.

Other measures used showed similar results, with 11.7% impairment of memory only, 8.3% impairment of attention and executive functions, and 11.6% impairment of multiple domains. Among them all, persistent loss of smell was a common factor, especially in cognitive impairment.

“The more we know about the causes or at least the people 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., professor at Pontificia Universidad Catolica Argentina, Buenos Aires, commented.

Other notable findings the scientists shared were the increased likelihood that intensive care unit stays increase the risk of dementia and that introducing a positive lifestyle change amid the pandemic may protect against symptoms of dementia. cognitive decline.

“This study is an example of how researchers from various 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 common goal of advancing the scientific understanding of Alzheimer’s disease, and the important contributions that such multicultural partnerships can make,” María Marquine, Ph.D., Associate Professor in the Departments of Medicine and Psychiatry and Director of Research on disparities at the division of geriatrics, gerontology, and palliative care at the University of California, San Diego, noted.


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