Genervon Presents Mechanisms of Actions in Alzheimer’s Disease, Including Results Confirming that GM6 Attenuates Alzheimer’s Disease in Mouse Model, in Part by Reducing Inflammation

PASADENA, Calif.--()--Following the closure of several research programs for Alzheimer’s disease, in early 2018 the FDA issued a release entitled “Draft Guidance for Industry: Early Alzheimer’s Disease: Developing Drugs for Treatment.” Encouraged by the proposed changes in the new guidance, Genervon’s research team reported new findings that its drug candidate GM6 attenuates Alzheimer’s disease (AD) in an early AD transgenic APP mice model. Application of GM6 over a 4-month period in young APP/ΔPS1 double-transgenic mice resulted in attenuation in Aβ peptide levels, reduction of inflammation and amyloid load, increased cathepsin B expression, and improved spatial orientation. In addition, treatment with GM6 increased brain nerve growth factor levels and tempered memory impairment by approximately 50% at the highest dose.

In the AD mouse models, inflammation seemed to play a key role in the disease process, and GM6 reduced cytokines (TNF-α, IL-1β, TGFβ, etc.) and inflammatory mediators (CD-68 and GFAP), which can contribute to pathogenesis, and modulated cathepsin B and cleavage of APP to Aβ.

These findings suggest that GM6 may modulate disease-determining pathways at an early stage to slow the histological and clinical progression of AD. The results will be presented on September 25, 2018 at the New York Academy of Science Symposium “Neuroimmunology – The Impact of Immune Function on Alzheimer’s Disease” and are available at https://www.genervon.com/animal-models-data/.

The anti-inflammation effect of GM6 is one of several mechanisms of actions that GM6 modulates in neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and AD. Other mechanisms include increased neurogenesis, decreased oxidative stress and apoptosis, increased extracellular matrix stability, increased cell adhesion, increased synaptic transmission, decreased Aβ toxicity, and the differential expression of disease-associated genes. Genervon’s research team recently summarized the mechanisms of action of GM6 for both ALS and AD; summaries are available on Genervon’s website (https://www.genervon.com/mechanisms-of-action/).

More generally, GM6 has been shown to have very good drug properties (study available at http://pub.iapchem.org/ojs/index.php/admet/article/view/547). GM6 was previously tested in a phase 2A ALS study, which confirmed the drug’s safety in humans, with no serious drug-related, treatment-emergent adverse effects. In that trial, Genervon observed favorable trends in GM6-treated patients, including a slowed decline in forced vital capacity and ALS Functional Rating Scale, along with decreased plasma abundance of ALS biomarkers (e.g., TDP-43, Tau, and SOD1). These results strongly suggest that GM6 has neurogenesis and anti-inflammatory effects in various neurodegenerative diseases, such as ALS and AD, with common underlying pathways.

Contacts

Genervon Biopharmaceuticals LLC
Emily Wang
info@genervon.com
http://www.genervon.com

Release Summary

GM6 attenuates Alzheimer’s disease in mouse model, in part by reducing inflammation, part of multiple pathways modulating neurodegenerative diseases

Contacts

Genervon Biopharmaceuticals LLC
Emily Wang
info@genervon.com
http://www.genervon.com