Bryostatin for Multiple Sclerosis

Overseen By Sarah M Planchon Pope, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Robert Fox

Must be taking: Disease modifying therapy

Must not be taking: Valproic acid, Lithium, Carbamazepine, others

Disqualifiers: Seizures, Unstable cardiovascular, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

Duration: 26 weeks

20 Participants Needed

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.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications before joining the trial. Specifically, you should not use vitamin E, valproic acid, lithium, carbamazepine, teriflunomide, dalfampridine, acetaminophen, ciprofloxacin, trimethoprim/sulfamethoxazole, St. John's Wort, or any potent/moderate inhibitors or inducers of certain enzymes. Additionally, you should not consume grapefruit juice during the study.

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. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

Is Bryostatin a promising drug for treating Multiple Sclerosis?

Yes, Bryostatin is a promising drug for treating Multiple Sclerosis. It has anti-inflammatory and antioxidant properties, helps repair nerve damage, and promotes the growth of new nerve cells. It has shown benefits in animal models and has a good safety profile in humans. ^{11 12 13 14 15}

How does the drug Bryostatin differ from other treatments for multiple sclerosis?

Bryostatin is unique because it not only reduces inflammation like other MS treatments but also promotes nerve cell growth and repair, reduces oxidative stress, and decreases harmful enzymes that damage the brain. It has shown potential in reversing symptoms even in later stages of the disease, which is not common with current treatments. ^{11 12 13 14 15}

Research Team

Robert Fox, MD

Principal Investigator

The Cleveland Clinic

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 have been in good health for the past 6 months and any chronic illness I have is under control.

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bryostatin treatment over a 26-week period, with 14 doses administered. Doses 1, 2, 8, and 9 are loading doses 20% higher than the fixed dose.

26 weeks

14 visits (in-person)

Safety and Exploratory Outcomes Evaluation

Evaluation of safety and exploratory outcomes, including various cognitive and MRI assessments.

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including long-term follow-up assessments.

12 weeks

Treatment Details

Interventions

• Bryostatin

Trial Overview The 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

Group I: Bryostatin 1 Experimental Treatment 1 Intervention

Participants in this arm will receive treatment with Bryostatin 1

Who Is Running the Clinical Trial?

Robert Fox

Lead Sponsor

Trials

2

Recruited

20+

Synaptogenix, Inc.

Collaborator

Trials

1

Recruited

20+

Findings from Research

In a study involving 43 patients with progressive multiple sclerosis, high dose biotin (300 mg/day) was found to be safe and well tolerated, with no evidence of toxicity or new brain lesions after one year.

Despite its safety, high dose biotin did not improve neurological function, and over one-third of patients experienced worsening symptoms, suggesting that while biotin is safe, it may not provide the expected benefits for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose biotin as treatment for progressive multiple sclerosis. Birnbaum, G., Stulc, J.[2018]

In a study of 178 patients with progressive multiple sclerosis, high-dose biotin supplementation did not show a significant improvement in disability progression after 12 months, with only 3.8% of patients experiencing an improved Expanded Disability Status Scale (EDSS) score.

While 47.4% of patients reported stability in their condition, a notable 25% experienced worsening symptoms, and 14% reported adverse events, indicating that high-dose biotin may not be an effective treatment in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice. Couloume, L., Barbin, L., Leray, E., et al.[2022]

In a study of 48 patients with progressive multiple sclerosis treated with high-dose biotin (MD1003) for one year, 27% showed significant clinical improvement as measured by the Expanded Disability Status Scale and other functional tests.

The treatment was also associated with increases in brain and cervical spinal cord volume in some patients, suggesting that MD1003 may have neuroprotective effects, particularly in less disabled individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003). Collongues, N., Kuhle, J., Tsagkas, C., et al.[2022]

Corticosteroid therapy, particularly high-dose intravenous methylprednisolone, is the primary treatment for acute exacerbations of multiple sclerosis, indicating its efficacy in managing sudden clinical changes.

Current immune-modulating agents have not shown enough clinical benefit to be routinely used for disease progression, highlighting the need for more targeted future treatments aimed at disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current therapy of multiple sclerosis. Francis, DA.[2019]

There is a critical need for effective treatment options for progressive multiple sclerosis (MS), and ongoing research is exploring new pathways and molecules that may offer reparative, remyelinating, or neuroprotective effects.

The review emphasizes the importance of standardized clinical outcome measures, including the Expanded Disability Status Scale and patient-reported outcomes, to effectively evaluate and demonstrate the benefits of new treatments in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome measures for progressive MS trials. Ontaneda, D., Cohen, JA., Amato, MP.[2018]

Alemtuzumab, natalizumab, and fingolimod are the most effective immunotherapies for preventing relapses in patients with relapsing-remitting multiple sclerosis, although their impact on preventing disability worsening is uncertain.

Fingolimod carries a high risk of treatment discontinuation due to adverse events, highlighting the importance of monitoring for side effects in patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis. Tramacere, I., Del Giovane, C., Filippini, G.[2016]

Dimethyl fumarate has been shown to significantly reduce relapse rates in patients with relapsing-remitting multiple sclerosis (MS), with a reduction of 34% to 49% in the proportion of patients experiencing relapses over two years, based on two phase III trials (DEFINE and CONFIRM).

The safety profile of dimethyl fumarate is comparable to placebo, with serious adverse effects occurring at similar rates; however, some patients experienced intolerable flushing and gastrointestinal issues, leading to discontinuation in 3% and 4% of cases, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. Venci, JV., Gandhi, MA.[2015]

The REGIMS registry is a multicenter observational study in Germany that collects data on the side effects of immunotherapies for multiple sclerosis, providing valuable insights into the long-term safety of these treatments.

By the end of 2019, REGIMS had recruited 1000 patients, primarily women with relapse-remitting MS, demonstrating the registry's ability to gather high-quality, real-world data despite facing logistical challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. Simbrich, A., Thibaut, J., Khil, L., et al.[2022]

In a study of 257 patients with relapsing-remitting multiple sclerosis, BG00012 at a dose of 240 mg three times daily significantly reduced the mean total number of new gadolinium-enhancing lesions by 69% compared to placebo, indicating strong efficacy in reducing disease activity.

BG00012 also decreased the annualized relapse rate by 32%, although this result was not statistically significant, and it was associated with some adverse events like abdominal pain and flushing, suggesting a generally favorable safety profile that supports further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Kappos, L., Gold, R., Miller, DH., et al.[2022]

Biologic immunotherapies, including monoclonal antibodies like natalizumab and ocrelizumab, have significantly improved treatment for multiple sclerosis, particularly during its inflammatory phase.

However, these therapies can lead to serious immunological side effects, such as secondary autoimmunity and immunodeficiency, which can complicate their safety and efficacy, exemplified by the market withdrawal of daclizumab due to severe adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis. Soleimani, B., Murray, K., Hunt, D.[2020]

Bryostatin-1, a natural compound derived from marine invertebrates, shows significant therapeutic potential for various neurological disorders, including Alzheimer's disease and traumatic brain injury, by targeting protein kinase C (PKC) to improve cognitive functions and provide neuroprotection.

Preclinical studies and clinical trials indicate that bryostatin-1 can effectively rescue deficits in spatial learning and memory, making it a promising candidate for treating CNS-related disorders, although further research is needed before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bryostatin-1: a promising compound for neurological disorders. Tian, Z., Lu, XT., Jiang, X., et al.[2023]

In two Phase II trials involving advanced Alzheimer's disease patients, bryostatin treatment led to significant improvements in cognitive function, as measured by the Severe Impairment Battery (SIB), with increases of 4.1 and 4.2 points above baseline at 13 weeks.

The pooled analysis of 95 patients confirmed that bryostatin treatment resulted in a statistically significant improvement in SIB scores over time compared to placebo, indicating its potential efficacy in enhancing cognitive function in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bryostatin Placebo-Controlled Trials Indicate Cognitive Restoration Above Baseline for Advanced Alzheimer's Disease in the Absence of Memantine1. Thompson, RE., Tuchman, AJ., Alkon, DL.[2022]

Nanoparticle-encapsulated Bryostatin-1 shows equal or greater efficacy than unmodified Bryostatin-1 in activating key proteins involved in neuroprotection, suggesting enhanced therapeutic potential for Alzheimer's disease.

In an Alzheimer's mouse model, treatment with nanoparticle-encapsulated Bryostatin-1 improved spatial learning and memory retention, indicating its potential as a cognitive enhancer in neurodegenerative conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schrott, L., Yi, P., Jackson, K., et al.[2021]

Bryostatin-1 shows promise as a multi-target treatment for multiple sclerosis (MS) due to its anti-inflammatory, antioxidant, and neuroprotective properties, which could address various aspects of the disease's pathology.

The drug not only reduces matrix metalloproteinases (MMPs) activity and blood-brain barrier damage but also promotes neurogenesis and the differentiation of oligodendrocyte progenitor stem cells, potentially aiding in remyelination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Inflammation, Suppression of Matrix Metalloproteinases, Induction of Neurogenesis, and Antioxidant Property Make Bryostatin-1 a Therapeutic Choice for Multiple Sclerosis. Safaeinejad, F., Bahrami, S., Redl, H., et al.[2020]

Bryostatin-1 (bryo-1) has shown significant benefits in a mouse model of multiple sclerosis (EAE), preventing the onset of neurological deficits and even reversing them after they have started, indicating its potential as a treatment for MS.

Bryo-1 promotes an anti-inflammatory response in immune cells, which could be particularly beneficial for treating the progressive phase of MS, a stage that currently lacks effective therapies, while also having a favorable safety profile in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bryostatin-1 alleviates experimental multiple sclerosis. Kornberg, MD., Smith, MD., Shirazi, HA., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

High dose biotin as treatment for progressive multiple sclerosis. [2018]

2. England pubmed.ncbi.nlm.nih.gov

High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003). [2022]

4. England pubmed.ncbi.nlm.nih.gov

The current therapy of multiple sclerosis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Clinical outcome measures for progressive MS trials. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. [2015]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Bryostatin-1: a promising compound for neurological disorders. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Bryostatin Placebo-Controlled Trials Indicate Cognitive Restoration Above Baseline for Advanced Alzheimer's Disease in the Absence of Memantine1. [2022]

13. United Arab Emirates pubmed.ncbi.nlm.nih.gov

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]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibition of Inflammation, Suppression of Matrix Metalloproteinases, Induction of Neurogenesis, and Antioxidant Property Make Bryostatin-1 a Therapeutic Choice for Multiple Sclerosis. [2020]

15. United States pubmed.ncbi.nlm.nih.gov

Bryostatin-1 alleviates experimental multiple sclerosis. [2021]