Trial Summary
What is the purpose of this trial?
This is a single-site, single-arm, single-dose, Phase 1 study of the safety of bryostatin in participants with multiple sclerosis (MS) receiving any disease modifying therapy (DMT).
Do I have to stop taking my current medications for this trial?
The trial requires that participants be off a DMT or on a stable dose of a DMT for at least 1 year before joining, and the dose should not change during the study unless necessary. Some specific medications must be stopped before screening, such as vitamin E, valproic acid, lithium, carbamazepine, teriflunomide, dalfampridine, acetaminophen, ciprofloxacin, trimethoprim/sulfamethoxazole, and St. John's Wort. Other medications will be reviewed on a case-by-case basis.
What data supports the idea that Bryostatin for Multiple Sclerosis (also known as: Bryostatin) is an effective treatment?
The available research does not provide data on Bryostatin for Multiple Sclerosis. Instead, it focuses on high-dose biotin as a treatment for progressive multiple sclerosis, showing that it may help reverse disability progression. There is no direct comparison to Bryostatin, so we cannot conclude its effectiveness for multiple sclerosis based on the provided information.12345
What safety data exists for Bryostatin in treating Multiple Sclerosis?
The provided research articles do not contain specific safety data for Bryostatin in the treatment of Multiple Sclerosis. They focus on other immunotherapies and biologic agents, such as dimethyl fumarate, oral fumarate, and various monoclonal antibodies. To find safety data for Bryostatin, one would need to look for studies or clinical trials specifically evaluating Bryostatin in the context of Multiple Sclerosis.678910
Is Bryostatin a promising drug for treating Multiple Sclerosis?
Eligibility Criteria
This trial is for individuals with multiple sclerosis (MS) who are currently on any disease-modifying therapy. The study is focused on understanding the safety of a single dose of Bryostatin in this specific patient population.Inclusion Criteria
Hospital Anxiety and Depression Scale <11
English-speaking
I am between 18 and 60 years old.
See 8 more
Exclusion Criteria
My kidney function is reduced with a creatinine clearance below 45ml/min.
I haven't had serious health issues in the last 6 months and have been cancer-free for 2 years, except for certain skin cancers.
My diabetes is not well-managed according to my doctor.
See 8 more
Treatment Details
Interventions
- Bryostatin (Protein Kinase C Modulator)
Trial OverviewThe trial is testing the safety profile of a medication called Bryostatin in patients with MS. It's a phase 1 study, which means it's an early-stage trial to assess how safe the drug is and how the body responds to it.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Bryostatin 1Experimental Treatment1 Intervention
Participants in this arm will receive treatment with Bryostatin 1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cleveland ClinicCleveland, OH
Loading ...
Who Is Running the Clinical Trial?
Robert FoxLead Sponsor
Synaptogenix, Inc.Collaborator
References
High dose biotin as treatment for progressive multiple sclerosis. [2018]Published data suggested high dose biotin improved patients with progressive MS. We wished to determine benefits and side effects of administering daily high dose biotin to patients with progressive multiple sclerosis in a large MS specialty clinic.
High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice. [2022]A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis.
Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003). [2022]High-dose pharmaceutical-grade biotin (MD1003) has positive effects on disability in progressive multiple sclerosis (PMS), but its mechanism of action remains unclear. The objective of our study was to quantify the effect of MD1003 in patients with PMS, using clinical response, plasma neurofilament light chain (pNfL) levels, and brain (BV) or cervical spinal cord volume (CSCV).
The current therapy of multiple sclerosis. [2019]The mainstay of treatment for multiple sclerosis in the U.K., and worldwide, remains corticosteroid therapy. High-dose pulses of intravenous methylprednisolone is currently the most favoured agent for acute exacerbations or a sudden acceleration in clinical course. Many patients who follow a more insidious decline rely on symptomatic treatments designed to ameliorate the chronic symptoms associated with their condition. Attempts to influence disease progression using a wide range of immune-modulating agents have not to date been of sufficient clinical benefit to justify their routine usage. With increasing understanding of the underlying disease mechanisms future treatments are being more specifically directed toward disease prevention.
Clinical outcome measures for progressive MS trials. [2018]Treatment options for progressive multiple sclerosis remain the main unmet need of the field. As the understanding of multiple sclerosis (MS) pathogenesis improves, new pathways and molecules will be tested for potential reparative, remyelinating, or neuroprotective effects. The clinical outcomes used will determine successful demonstration of beneficial treatment effects to regulatory agencies, clinicians, and persons with MS. This review focuses on clinical outcome measures including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and novel composite measures of disability. The paper also covers cognitive outcomes and screening tests for use in clinical trials. The growing importance of patient-reported outcomes and their suitability for clinical trials is also presented. The review aims to create consensus in regard to these topics and suggestions for future research.
Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis. [2016]What immunotherapies for multiple sclerosis are associated with the greatest benefit and highest risk of discontinuation due to adverse events in patients with relapsing-remitting multiple sclerosis?
Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. [2015]To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS).
Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. [2022]The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks.
Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. [2022]Oral fumarate (BG00012) might have dual anti-inflammatory and neuroprotective effects. Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing-remitting multiple sclerosis.
Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis. [2020]Biologic immunotherapies have transformed the treatment landscape of multiple sclerosis. Such therapies include recombinant proteins (interferon beta), as well as monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab and ocrelizumab). Monoclonal antibodies show particular efficacy in the treatment of the inflammatory phase of multiple sclerosis. However, the immunological perturbations caused by biologic therapies are associated with significant immunological adverse reactions. These include development of neutralising immunogenicity, secondary immunodeficiency and secondary autoimmunity. These complications can affect the balance of risks and benefits of biologic agents, and 2018 saw the withdrawal from the market of daclizumab, an anti-CD25 monoclonal antibody, due to concerns about the development of severe, unpredictable autoimmunity. Here we review established and emerging risks associated with multiple sclerosis biologic agents, with an emphasis on their immunological adverse effects. We also discuss the specific challenges that multiple sclerosis biologics pose to drug safety systems, and the potential for improvements in safety frameworks.
Bryostatin-1: a promising compound for neurological disorders. [2023]The central nervous system (CNS) is the most complex system in human body, and there is often a lack of effective treatment strategies for the disorders related with CNS. Natural compounds with multiple pharmacological activities may offer better options because they have broad cellular targets and potentially produce synergic and integrative effects. Bryostatin-1 is one of such promising compounds, a macrolide separated from marine invertebrates. Bryostatin-1 has been shown to produce various biological activities through binding with protein kinase C (PKC). In this review, we mainly summarize the pharmacological effects of bryostatin-1 in the treatment of multiple neurological diseases in preclinical studies and clinical trials. Bryostatin-1 is shown to have great therapeutic potential for Alzheimer's disease, multiple sclerosis, fragile X syndrome, stroke, traumatic brain injury, and depression. It exhibits significant rescuing effects on the deficits of spatial learning, cognitive function, memory and other neurological functions caused by diseases, producing good neuroprotective effects. The promising neuropharmacological activities of bryostatin-1 suggest that it is a potential candidate for the treatment of related neurological disorders although there are still some issues needed to be addressed before its application in clinic.
Bryostatin Placebo-Controlled Trials Indicate Cognitive Restoration Above Baseline for Advanced Alzheimer's Disease in the Absence of Memantine1. [2022]In pre-clinical studies of Alzheimer's disease (AD) transgenic mice, bryostatin restored synaptic connections, prevented neuronal death, reduced amyloid plaques, and reduced neurofibrillary tangles.
Nanoparticle-Encapsulated Bryostatin-1 Activates α-Secretase and PKC Isoforms In vitro and Facilitates Acquisition and Retention of Spatial Learning in an Alzheimer's Disease Mouse Model. [2021]Alzheimer's disease (AD) animal models have revealed neuroprotective actions of Bryostatin-1 mediated by activation of novel PKC isoforms, suppression of beta-amyloid and downregulation of inflammatory and angiogenic events, making Bryostatin-1 an attractive candidate for attenuating AD-associated neural, vascular, and cognitive disturbances.
Inhibition of Inflammation, Suppression of Matrix Metalloproteinases, Induction of Neurogenesis, and Antioxidant Property Make Bryostatin-1 a Therapeutic Choice for Multiple Sclerosis. [2020]Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and myelin damage. Pro-inflammatory cytokines, oxidative stress, high level of matrix metalloproteinases (MMPs) activity and blood-brain barrier (BBB) damage, immune-mediated destruction of myelin and neuron loss are involved in the pathogenesis of MS. The currently approved treatments for MS include injectable drugs (interferon-β and glatiramer acetate), oral drugs (fingolimod), and monoclonal antibodies (natalizumab). The mentioned therapeutic choices are mostly focused on the inhibition of inflammation. Therefore, the search for a multi-target therapeutic choice remains unchallenged. It seems that a drug with anti-inflammatory, oxidative stress inhibitory, reduction of MMPs activity, and neurogenesis stimulatory properties may be effective for treatment of MS. In this regard, Bryostatin-1 as a macrolide and marine natural product has been selected as a therapeutic choice. Studies indicate that Bryostatin-1 has anti-inflammatory and antioxidant properties and decreases MMPs level and BBB damage. Furthermore, Bryostatin-1 has a neuroprotective effect and promotes neurogenesis and differentiation of oligodendrocyte progenitor stem cells as a critical step for remyelination/myelogenesis. Based on these properties, we hypothesized here that Bryostatin-1 is an effective treatment in MS.
Bryostatin-1 alleviates experimental multiple sclerosis. [2021]Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS. In the present study, we show that bryo-1 provides marked benefit in mice with experimental autoimmune encephalomyelitis (EAE), an experimental MS animal model. Preventive treatment with bryo-1 abolishes the onset of neurologic deficits in EAE. More strikingly, bryo-1 reverses neurologic deficits after EAE onset, even when treatment is initiated at a late stage of disease when peak adaptive immunity has subsided. Treatment with bryo-1 in vitro promotes an anti-inflammatory phenotype in antigen-presenting dendritic cells, macrophages, and to a lesser extent, lymphocytes. These findings suggest the potential for bryo-1 as a therapeutic agent in MS, particularly given its established clinical safety. Furthermore, the benefit of bryo-1, even in late treatment of EAE, combined with its targeting of innate myeloid cells suggests therapeutic potential in progressive forms of MS.