Synaptogenix cleared to launch Phase 1 trial of bryostatin-1 in MS

The U.S Food and Drug Administration (FDA) authorized an investigational new drug application from Synaptogenix, clearing the company to launch a clinical trial to test whether its lead candidate bryostatin-1 can prevent cognitive decline in people with multiple sclerosis (MS).

The open-label, Phase 1 clinical trial (NCT06190912), to be conducted at a single site at the Cleveland Clinic Neurological Institute’s Mellen Center for Multiple Sclerosis, will be led by Robert Fox, MD, vice-chair for research at the institute.

It will enroll about 20 adults with MS to study the therapy’s safety and impact on neuroinflammation, as well as on cognition, disease severity, walking function, dexterity, and quality of life.

Additional exploratory measures include identifying changes in imaging biomarkers that can provide more information about how the therapy affects the brain, which will be examined using a 7-tesla MRI scanner that’s able to acquire images with very high definition.

“Our study will apply state-of-the-art MRI technology together with behavioral and cognitive measures to evaluate treatment with investigational bryostatin-1,”  Fox said in a company press release. “Research and development of this drug could yield potential benefits for patients with MS.”

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Understanding cognitive impairment

Cognitive impairment is a common symptom of MS, estimated to affect more than half of all patients. It can have a significant impact on a person’s life, limiting the ability to participate in work and other activities.

However, “the mechanisms underlying cognitive impairment remain obscure and inadequately studied in clinical trials,” said Alan Tuchman, MD, CEO of Synaptogenix. “We seek to address this unmet need, with minimal expense, and look forward to launching our effort by enrolling/dosing our first patient in the near future.”

Bryostatin-1 is a brain-penetrant small molecule that activates an enzyme called protein kinase C. This enzyme is key for maintaining the health of synapses, the sites where adjacent nerve cells communicate, and is also important for learning and memory.

Poor synapse health is believed to drive cognitive impairment in MS and other neurological disorders.

In addition to boosting cognition, the therapy seems to have some anti-inflammatory effects, which may help ease the inflammatory attacks that drive disability progression in people with MS.

Preclinical studies in a mouse model of MS have demonstrated that bryostatin-1 prevented synapse loss and nerve cell death, reduced inflammation, and reversed neurological deficits in the animals, even in later disease stages.

“These preclinical data suggest that bryostatin-1 has promising potential as a therapeutic agent for MS and perhaps more so for progressive forms of MS,” Daniel Alkon, MD, Synaptogenix’s president and chief scientific officer.

The upcoming Phase 1 trial will have all patients receiving about 14 doses of bryostatin-1, given via weekly, 45-minute-long infusions into the bloodstream, on top of their standard MS treatments. The main trial will last 28 weeks, after which participants may continue to be followed for an additional 12 weeks.

Bryostatin-1 is also being developed as a potential treatment for Alzheimer’s disease and fragile X syndrome, among other neurological diseases.