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, directed attentional focus, 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).
SOURCE Blanchette Rockefeller Neurosciences Institute