Huntington, W.Va.--Researchers at the Blanchette Rockefeller Neurosciences Institute (BRNI) and the Marshall University Joan C. Edwards School of Medicine announced their findings from a new study entitled, "PSEN1 Variant in a Family with Atypical AD." An Alzheimer patient with very severe disease, genetically confirmed to have a known variant of PSEN1, showed promising benefits during treatment with the drug Bryostatin 1. Genetically confirmed Alzheimer’s patients as severely advanced as patient IV-18 have not shown this level of clinical improvement previously with other treatment(s).
“We are very encouraged by the clinical improvements observed in patient IV-18. Nevertheless, controlled clinical trials are necessary to demonstrate safety and efficacy. BRNI believes, however, that this patient’s response is supportive evidence that activation of Protein Kinase C (PKC) by potent activators such as Bryostatin, with both pre-clinical synaptogenic and anti-amyloid efficacies, could be a viable therapeutic approach for the treatment of severe Alzheimer disease”, said Dr. Daniel Alkon, Scientific Director of BRNI and Chief Scientific Officer of Neurotrope BioScience, Inc. Neurotrope Bioscience Inc., which has licensed this novel therapeutic approach from the BRNI, has recently announced positive results of its Phase 2a safety study and is planning a larger proof of concept study in severe Alzheimer patients, which is intended to advance Bryostatin for the treatment of this disease.
Based on a number of BRNI pre-clinical and autopsy-validated human studies that have implicated PKC deficits as a cause of Alzheimer's disease, patient IV-18 was treated with the potent PKC epsilon activator, Bryostatin. This drug was administered by intravenous infusion once a week for the first three weeks of each month. Within two weeks of the initiation of treatment, patient IV-18 showed clinical improvements that included word vocalization,directedattentionalfocus, restoration of swallowing, increased responses to verbal commands, and some improvement of range of limb motion. These improvements persisted for approximately eight weeks, despite an episode of severe pneumonia that required intubation and hospitalization for four weeks.
BRNI was contacted by a West Virginian whose family suffered from high incidence of early onset dementia. Dementia in one family member, identified in study as IV-18, began at the age of 27 and included an inability to speak or swallow as well as immobilizing spasticity, although the patient retained some awareness and attentiveness. On behalf of the family member, BRNI sought and gained allowance from the Food and Drug Administration to proceed with compassionate treatment of patient IV-18 with Bryostatin, a drug that BRNI has been researching for over a decade, for treatment of cognitive disorders. The National Cancer Institute provided Bryostatin for this patient’s treatment.
Investigators at Marshall University’s School of Medicine working in close collaboration with BRNI constructed the pedigree of the West Virginia family in which members from five generations exhibited very early onset Alzheimer's dementia. By performing genomic analysis on blood samples from two of the West Virginia family members and comparing it with blood analysis from two family members in Michigan, the Marshall University Genomics Core researchers determined that this family has a unique expression of a very rare variant in the PSEN1 gene. This study provides the first description of the clinical presentation of patients with the variant earlier reported in French family (ALZ047).
The results of this study, co-authored by James Denvir, Ph.D.; Shirley Neitch, M.D.; Jun Fan, Ph.D.; Richard M. Niles, Ph.D.; Goran Boskovic, Ph.D.; Bernard G. Schreurs, Ph.D.; Donald A. Primerano, Ph.D.; and Daniel L. Alkon, M.D., can be found in an early online edition of the Journalof Alzheimer's Disease. The printed article will appear in Volume 46, Issue 2 of the Journal.
About the Blanchette Rockefeller Neurosciences Institute
The Blanchette Rockefeller Neurosciences Institute (www.brni.org) is a unique, independent, non-profit institute dedicated to the study of memory and finding solutions to memory disorders. BRNI was founded in 1999 in memory of Blanchette Ferry Hooker Rockefeller, an Alzheimer patient and mother of U.S. Senator John D. Rockefeller IV. BRNI is operated in alliance with West Virginia University as well as in collaboration with other academic institutions.
About the Marshall University Joan C. Edwards School of Medicine
The Marshall University Joan C. Edwards School of Medicine (www.musom.marshall.edu) is a community-based, Veterans Affairs affiliated medical school dedicated to providing high quality medical education and postgraduate training programs to foster a skilled physician workforce to meet the unique healthcare needs of West Virginia and Central Appalachia. Building upon its medical education foundation, the school seeks to develop centers of excellence in clinical care, including primary care in rural underserved areas, focused and responsive programs of biomedical science graduate study, biomedical and clinical science research, academic scholarship and public service outreach.
Neurotrope Bioscience Inc., the operating subsidiary of Neurotrope, Inc. (OTCQB:NTRP), was formed in October 2012 principally to license, develop and commercialize various novel therapeutic and diagnostic technologies from the BRNI which are focused on the development of conventional small molecules that are extraordinarily potent in the activation of the enzyme PKCe. PKCe has been shown to play a central role in the regrowth or repair of nervous tissues, cells or cell products. Neurotrope’s pipeline, under its license from BRNI, includes the drug candidate, Bryostatin, for the treatment of Alzheimer’s disease, and a minimally invasive, diagnostic biomarker analysis system which would assess the presence of Alzheimer’s in patients. In addition, Neurotrope has a world-wide, exclusive license agreement with the Icahn School of Medicine at Mount Sinai located in New York City to utilize its proprietary information and data package for the use of Bryostatin-1 in the treatment of Niemann-Pick Type C Disease, a rare disease, mostly of children who are afflicted with Alzheimer-like symptoms. Also, the Company, under its BRNI license, has the rights to develop the licensed technology for other cognitive dysfunctions, including orphan diseases, such as Fragile X Syndrome. As part of their clinical development plan, Neurotrope is also exploring synthesis of Bryostatin and other potent PKC activators.
Bryostatin, originally identified by Dr. George Pettit of the University of Arizona, is a natural product produced by a marine invertebrate organism called Bugula neritina and is isolated from organic matter harvested from the ocean. Several variations of this complex product have been achieved in recent years in various academic chemistry laboratories.
For additional information, please contact:
Karen Shuler Stakem
Leah C. Payne
Marshall University Joan C. Edwards School of Medicine
Date Posted: Monday, March 30, 2015