Aphios Presents Alzheimer's Disease Research Data at Neuroscience 2012 Conference, New Orleans, LA
October 15, 2012
Woburn, MA – Aphios Corporation announced today that, in collaboration with researchers at Louisiana State University Health Sciences Center, Shreveport, LA (LSUHSC), it will present "Efficacy of a nanoparticles-encapsulated form of Bryostatin-1 on alpha-secretase and protein kinase C (PKC) isoform activation and cognitive enhancement in an Alzheimer's disease model" at the Neuroscience 2012 conference, Society of Neuroscience 42nd Annual Meeting, being held in New Orleans, LA from October 13 to 17, 2012.

Alzheimer's disease (AD) is the third leading cause of death in America and among the highest in the industrial world. AD is a devastating age-related neurological disorder that affects more than 4.5 million Americans and more than 10 million people worldwide. Experts estimate that 22 million people around the world and more than 8 million Americans will be afflicted with this disease by 2025.

Recent research suggests that Bryostatin-1 is neuroprotective via activation of protein kinase C isoforms, downregulation of pro-inflammatory and angiogenic processes and the suppression of beta amyloid. Alzheimer's disease (AD) has been associated with these events and therefore Bryostatin-1 is an attractive candidate for ameliorating AD cognitive deficits. In an in vitro neuroblastoma model of APP processing, we found that several nanoparticles-encapsulated formulations of Bryostatin-1 (ALZ-04 etc.) stimulated α-secretase, PKC-δ and PKC-ε activation to an equal or greater extent than native Bryostatin-1 in an ethanol vehicle. In vitro comparison of α-secretase activation in SH-SY5Y neuroblastoma cells showed that after 3 hours of treatment, 1 nanomolar native Bryostatin-1 increased α-secretase activity by ~2.5 fold over vehicle control compared to a ~4.25 fold increase in activity using ALZ-04 nanoencapsulated Bryostatin-1.

The Bryostatin-1 nanoparticles formulation 'ALZ-04,' which showed high potency in in vitro models compared to native Bryostatin-1, was investigated in our mouse model of AD cognition and spatial memory. We treated 6.5 to 8 month old mice from the BC3-Tg(APPswe, PSEN1 dE9) 85Dbo/J mouse strain. This strain incorporates the human 'Swedish' (swe) amyloid precursor protein and presenilin mutations that are associated with progressive human AD. Mice were treated with a nanoparticles-encapsulated Bryostatin-1 formulation (ALZ-04, 1, 2.5, and 5 µg/ mouse) by oral gavage 3 times the week prior to testing and then daily during 5 days of testing (4 trials per day). Bryostatin-1 nanoparticles-treated mice had shorter latencies and distances to find the escape platform across the acquisition phase than the vehicle-treated Tg mice. Following a two-week drug free period, the mice received a single day of retention testing. Bryostatin-1 nanoparticles- treated mice continued to have shorter latencies to find the escape platform than the vehicle-treated Tg mice indicating a stronger retention of the spatial memory. These data suggest that a nanoparticles-encapsulated formulation of Bryostatin-1 can be made orally bioavailable to treat cognitive decline associated with AD.

Aphios® Corporation is a clinical stage biotechnology company developing green, enabling technology platforms for improved drug discovery and manufacturing, nanotechnology drug delivery and pathogenic drug safety. Based on these platforms, Aphios is developing enhanced therapeutic products for health maintenance, disease prevention and the treatment of certain cancers, infectious diseases and central nervous system disorders, such as Alzheimer's Disease. To learn more about Aphios, visit us at www.aphios.com.

LSUHSC is actively involved in several studies on neurovascular degeneration including Multiple Sclerosis and Parkinson's disease, as well as AD. LSUHSC campus family includes Schools of Medicine, Allied Health Professions and Graduate Studies, and three acute care hospitals. LSUHSC is home to the Feist-Weiller Cancer Center and a Center of Excellence in Arthritis and Rheumatology, an accredited Children's Hospital, a regional Burn Center and a Level One Trauma Center serving communities across Northwest Louisiana, East Texas and Southwest Arkansas.

The project described is supported by Grant Number R44AG034760 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.