Phase 1 trial of bryostatin-1 in MS expected by year’s end

Synaptogenix is teaming up with Cleveland Clinic for a Phase 1 clinical trial involving people with multiple sclerosis (MS) that will test the company’s lead candidate, bryostatin-1 — a therapy designed to prevent cognitive deficits in MS patients.

“We are moving forward with our clinical development plans for bryostatin-1 in MS in collaboration with Cleveland Clinic,” Alan Tuchman, MD, CEO of Synaptogenix, said in a company press release.

Management of the upcoming trial will be led by Cleveland Clinic, which also will file an application to the U.S. Food and Drug Administration asking for clearance to begin the study. Assuming the regulatory agency gives the go-ahead, the study is expected to start before the end of this year.

“The planned clinical trial will be held at Cleveland Clinic Neurological Institute’s Mellen Center for Multiple Sclerosis, one of the largest and most comprehensive programs for MS care and research worldwide,” Tuchman said.

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Robert Fox, MD, the vice-chair for research at the Neurological Institute, will serve as the trial’s principal investigator.

“We look forward to working together to explore the safety and potential activity of bryostatin-1 on cognitive impairment in multiple sclerosis,” Fox said.

“Cognitive impairment is a major unmet need in the treatment of people living with MS and we look forward to exploring the potential impact of this investigational drug,” Fox added.

The final agreement between Synaptogenix and Cleveland Clinic comes more than a year after the company announced plans to test the experimental therapy in MS patients.

Originally developed by Neurotrope, from which Synaptogenix was derived, bryostatin-1 is a brain-penetrant small molecule that works by activating an enzyme called protein kinase C.

This enzyme is crucial for maintaining the health of synapses, or the points of near contact between nerve cells where they transmit signals to one another. In MS and other neurological disorders, poor synapse health is thought to play a critical role in driving disease symptoms like cognitive impairment.

“We do not believe that the elimination of synapses caused by MS has been addressed by any marketed drugs or drug strategies to date, and we believe this gap in MS treatment options presents a significant opportunity,” Tuchman said.

In preclinical studies using a mouse model of MS, treatment with bryostatin-1 was shown to prevent and reverse neurological deficits and reduce inflammation in the animals.

Daniel Alkon, MD, president and chief scientific officer at Synaptogenix, noted that the two collaborators will be working to find biomarkers that can assess the impact of bryostatin-1 on the brain in people with MS.

“Cleveland Clinic [is] a leading provider of advanced magnetic resonance imaging (MRI) technology for brain imaging,” Alkon said.

In addition to identifying biomarkers that can provide more information about how the therapy affects the brain of MS patients, the planned Phase 1 trial will be designed to evaluate bryostatin-1’s safety and potential effects on cognitive function.

Bryostatin-1 may improve cognitive function in MS, and address other primary components of the disease.

“Given the drug’s putative restorative mechanisms of action, its potential unique ability to drive synaptic formation (regeneration), its anti-inflammatory activity, and its potential for remyelination (replacement of [the] lost insulating sheath surrounding nerve cells), bryostatin-1 may improve cognitive function in MS, and address other primary components of the disease,” Alkon said.

Synaptogenix also is developing bryostatin-1 as a potential treatment for other neurological disorders, including Alzheimer’s disease and fragile X syndrome.

“As we move forward with this study, we will continue to pursue other potential business endeavors including the identification of other assets for clinical development,” Tuchman said.