The company, which will conduct the trial in collaboration with the The Nemours/Alfred I. duPont Hospital for Children, in Wilmington, Delaware, have not given a date for the study’s start.
The trial will assess the safety and tolerability of Bryostatin-1, currently being tested in a Phase 2 study in patients with Alzheimer’s disease (NCT03560245).
“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, [the enzyme] PKC epsilon, was shown in extensive pre-clinical testing to restore these lost synaptic structures,” Daniel Alkon, MD, president and chief scientific officer of Neurotrope, said in a press release.
Fragile X syndrome is characterized by synaptic immaturity, cognitive impairment, and behavioral changes. Bryostatin-1 activates PKC epsilon and promotes the development of synapses and synaptic maturation, which are dysfunctional in these patients. The synapse is the contact site between nerve cells where an electrical or chemical signal is transmitted from one nerve cell to another.
The pilot open-label clinical trial will dose fragile X patients who are at least 8 and younger than 18. Researchers will use a dosing regimen similar to that being tested in Alzheimer’s patients.
“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,” Alkon said.
In addition to safety and tolerability, the study will test parameters such as working memory and language, as well as functional outcomes 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,” said Charles Ryan, MD, chief executive officer of Neurotrope.
Previous studies using a pre-clinical model of fragile X syndrome have shown that administration of Bryostatin-1 led to benefits similar to those produced in mouse models of Alzheimer’s disease. In particular, researchers found that Bryostatin-1 was able to restore synaptic structures.
“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,” said Craig Erickson, MD, a leading researcher in the fragile X syndrome field.
Bryostatin-1 has received Orphan Drug status for treatment of fragile X syndrome from the Food and Drug Administration (FDA). This designation is given to potential therapies for rare diseases, affecting fewer than 200,000 patients in the U.S. and includes a number of incentives: seven years of U.S. market exclusivity (if the therapy is approved), tax credits for clinical research costs, assistance with clinical trial design, and exemption from Prescription Drug User Fee Act (PDUFA) filing fees.