Neurotrope Enters into Collaboration with the Nemours / Alfred I. duPont Hospital for Children to Initiate a Clinical Trial in Fragile X Syndrome
NEW YORK, Sept. 5, 2018 /PRNewswire/ — Neurotrope Inc. (NTRP) a clinical-stage biopharmaceutical company developing novel therapies for neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease (AD), is announcing a collaboration with The Nemours / Alfred I. duPont Hospital for Children (“Nemours”) to initiate a clinical trial in children with Fragile X Syndrome (“Fragile X”). The planned protocol for the pilot open-label trial will dose Fragile X patients from 8 to less than 18 years of age, using a dosing regimen similar to that being tested in AD patients. In addition to the primary objective of safety and tolerability, measurements will be made of working memory, language and other functional aspects such as anxiety, repetitive behavior, executive functioning, and social behavior. “We are delighted to be collaborating with clinical scientists at Nemours on this important study for Fragile X. As one of the premier children’s hospitals in the United States, this hospital has both the patient population and the clinical team required to execute this study,” stated Dr. Charles Ryan, Chief Executive Officer of Neurotrope.
Fragile X is characterized by synaptic immaturity, cognitive impairment, and behavioral changes that currently have no effective therapeutics. The disorder is caused by transcriptional shutdown in neurons of the FMR1 gene product, the Fragile X mental retardation protein (FMRP). Fragile X, a childhood neurological disorder that afflicts approximately 135,000 individuals in the U.S., is characterized by widespread loss of synaptic connections and occurs early in the neurological development process.
“Alzheimer’s disease and Fragile X have a common devastating consequence in the brain: the loss of functional and anatomically normal synaptic networks – the loss of the brain’s “wiring.” Bryostatin’s target, PKC epsilon, was shown in extensive pre-clinical testing to restore these lost synaptic structures. Neurotrope is collaborating with Nemours on an early clinical trial with dose frequency that is similar to the completed Phase 2 trial with AD patients that suggested promising improvement in cognitive functions,” stated Dr. Daniel Alkon, President and Chief Scientific Officer of Neurotrope.
With a transgenic, pre-clinical model of Fragile X, Bryostatin-1 caused benefits similar to those produced in AD transgenic mice – restoration of synaptic structures. Bryostatin-1 is a relatively selective PKC epsilon activator which appears to induce synaptogenesis and synaptic maturation by activating synaptic growth factors present in the brain. Such cognitive benefits and synaptic restoration have not been demonstrated by any drugs tested in pre-clinical Fragile X models. Bryostatin-1 has been granted Orphan Drug status for the treatment of Fragile X by the Food and Drug Administration (“FDA”). “The mechanism of Bryostatin-1 is novel compared to all prior drug treatments studied in Fragile X. It will be important to explore this mechanism in an early phase Fragile X human study. Early signs of positive target engagement and potential change on quantitative outcome measures will work to justify a larger-scale future study,” stated Professor Craig Erickson, MD, a leading authority on Fragile X.
Pre-clinical studies have shown that chronic treatment with Bryostatin-1 rescues young Fragile X mice from the disorder phenotypes, including normalization of most Fragile X abnormalities in: 1) hippocampal brain-derived neurotrophic factor expression; 2) postsynaptic density-95 levels; 3) transformation of immature dendritic spines to mature synapses; 4) densities of the presynaptic and postsynaptic membranes, and; 5) spatial learning and memory. Our pre-clinical results demonstrate that synaptic and cognitive function of young Fragile X mice can potentially be normalized through pharmacological treatment without down-regulation of mGluR5 and that Bryostatin-1-like agents may represent a novel class of drugs to treat the effects of Fragile X at a young age and in adults. (J Pharmacol Exp Ther. 2016 May;357(2):300-10).
Neurotrope is at the forefront of developing a new approach to combating AD and other neurodegenerative diseases. The Company’s world-class science offers the potential to realize a paradigm shift to overcome one of today’s most challenging clinical problems — finding a way to slow or even prevent the progression of AD.