DUOC-01 for Multiple Sclerosis
(DUOC for MS Trial)
Recruiting in Palo Alto (17 mi)
Overseen byBeth Shaz, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Joanne Kurtzberg, MD
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests the safety of injecting special cells from umbilical cord blood into the spinal fluid of adults with a severe form of multiple sclerosis. The goal is to see if these cells can help repair nerve damage and reduce inflammation. About 20 participants will be monitored over time to check for any improvements and side effects. Umbilical cord blood cells have been studied for their potential to treat neurological disorders, including spinal cord injuries, due to their ability to produce neurotrophic factors and modulate immune responses.
Do I have to stop taking my current medications for the trial?
No, you don't have to stop taking your current medications. Participants on disease-modifying therapies must continue them during the study, although changes can be made if needed for clinical reasons.
What data supports the idea that DUOC-01 for Multiple Sclerosis is an effective treatment?
The available research does not provide specific data on the effectiveness of DUOC-01 for Multiple Sclerosis. Instead, it discusses other treatments like ocrelizumab, dexamethasone, dimethyl fumarate, natalizumab, and MD1003. These treatments have shown varying levels of effectiveness in managing symptoms or slowing the progression of Multiple Sclerosis. For example, ocrelizumab has been proven effective in clinical studies, and MD1003 has shown improvement in disability outcomes. However, there is no direct comparison or data available for DUOC-01 in the provided information.
12345What safety data is available for DUOC-01 treatment in multiple sclerosis?
The provided research does not contain any safety data specifically related to DUOC-01, DUOC-01 cells, or DUOC cells for multiple sclerosis. The studies mentioned focus on other treatments such as anti-TNFα therapy, glatiramer acetate, dimethyl fumarate, and ocrelizumab, none of which are related to DUOC-01.
678910Is the treatment DUOC-01 a promising treatment for Multiple Sclerosis?
The provided research articles do not mention DUOC-01 or its potential as a treatment for Multiple Sclerosis. Therefore, based on the available information, we cannot determine if DUOC-01 is a promising treatment for this condition.
1112131415Eligibility Criteria
Adults aged 18-65 with Primary Progressive Multiple Sclerosis (PPMS) and an EDSS score of 3.0-6.5 are eligible for this trial. Participants must have stable MS, a matched umbilical cord blood unit available, and agree to effective contraception during the study plus six months after treatment. Exclusions include prior transplants or cell therapies within three years, other progressive neurological disorders, recent malignancies except certain skin cancers, active immune diseases besides MS, MRI or lumbar puncture contraindications, severe infections, ventilatory support need, recent suicidal behavior or ideation.Inclusion Criteria
My disability score is between 3.0 and 6.5, and it has been stable for the last 6 months.
I have been diagnosed with primary progressive MS.
Able to complete a written informed consent prior to any study assessments
+6 more
Exclusion Criteria
I have not had a severe infection in the last 2 weeks.
I have seizures that medication cannot control.
Pregnant or breastfeeding or intention to become pregnant during the study
+13 more
Participant Groups
The trial is testing DUOC-01 cells administered intrathecally (into the spinal canal) to treat PPMS. DUOC-01 is derived from human umbilical cord blood cells aimed at treating neurodegenerative conditions. This Phase 1a open-label single-center study will enroll about 20 participants and explore changes in MS scores, brain MRI results, and blood biomarkers.
1Treatment groups
Experimental Treatment
Group I: DUOC-01Experimental Treatment1 Intervention
Intrathecal Infusion of DUOC-01 and hydrocortisone. Cohort 1: 10 million cells Cohort 2: greater than 10 to 25 million cells Cohort 3: greater than 25 to 50 million cells
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke University Medical CenterDurham, NC
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Who Is Running the Clinical Trial?
Joanne Kurtzberg, MDLead Sponsor
References
[Additional possible mechanisms of the action of ocrelizumab in multiple sclerosis on example of a case-report]. [2019]Anti-B-cells products, including the anti-CD20 monoclonal antibody ocrelizumab, are widely coming to multiple sclerosis (MS) therapy. Its clinical-MRI efficacy in MS with relapses as well in primary progressive MS (PPMS) was proved by three phase III clinical studies. One example of the use of ocrelizumab use in aggressive MS showed the possibility of action on the leptomeningeal folliculi, seen at contract-enhancing MRI images.
Analysis of peripheral blood lymphocyte phenotype and function during dexamethazone treatment of progressive multiple sclerosis. [2019]Five patients with chronic progressive multiple sclerosis (MS) and three control patients with lumbar disc herniation were treated with dexamethazone during 14 days. The effect on peripheral blood T-cell subsets and on the proliferative response of peripheral blood mononuclear cells (PBMC) to pokeweed mitogen (PWM) and anti-mu antibody was analyzed. Before treatment, the proportion of CD3+ and CD4+ PBMC was similar in MS and control patients, but the proportion of CD8+ and DR+ PBMC was lower and the PBMC were less responsive to anti-mu stimulation in MS patients compared to controls. Steroid treatment induced reversible granulocytosis and lymphocytosis. CD3+ and CD4+ cells increased and DR+ cells decreased in MS patients but not in controls. Proliferation of anti-mu stimulated PBMC increased in MS-patients during the two weeks of treatment, but decreased in controls. The enhancement in the MS patients of pre-existing immune abnormalities suggests that a cautious attitude is warranted in the use of steroid treatment in chronic progressive MS.
Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS. [2022]The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS).
Getting specific: monoclonal antibodies in multiple sclerosis. [2014]For more than a decade the only therapies that were available for multiple sclerosis (MS) were two immunomodulatory drugs-interferon beta and glatiramer acetate-and the immunosuppressant mitoxantrone. Natalizumab, a monoclonal antibody against alpha4 integrin, has been approved by the US Food and Drug Administration and the European Medicines Agency on the basis of its higher efficacy than the available treatments and its good safety profile. Monoclonal antibodies that are already licensed to treat other diseases, such as cancer and autoimmune diseases, are being tested for the treatment of MS. Additionally, novel targets are currently being investigated for MS. The therapeutic use of monoclonal antibodies was initially viewed with great scepticism owing to the high rates of sensitisation against mouse proteins, their pharmacokinetic properties, and the difficulties in their production. However, most of these problems have been overcome, and monoclonal antibodies are now among the most promising therapies for MS.
Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. [2021]There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort.
Demyelinating Events Following Initiation of Anti-TNFα Therapy in the British Society for Rheumatology Biologics Registry in Rheumatoid Arthritis. [2021]To establish the incidence of demyelination in patients who have received anti-tumor necrosis factor alpha (anti-TNFα) therapy, through analysis of adverse events reported in a prospective cohort of patients receiving biological therapies.
Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. [2021]Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting.
Pregnancy Outcomes from the Branded Glatiramer Acetate Pregnancy Database. [2022]Appropriate counseling and treatment for women with multiple sclerosis (MS) who may become pregnant requires an understanding of the effects of exposure to disease-modifying therapies (DMTs) during pregnancy. Current reports and studies are limited in their usefulness, mostly by small sample size. Branded glatiramer acetate (GA) is a DMT approved for the treatment of relapsing forms of MS. For more than 2 decades, it has been shown to be efficacious and to have a favorable safety profile. The Teva Pharmaceutical Industries Ltd global pharmacovigilance database comprises data from more than 7000 pregnancies, during which women with MS were exposed to treatment with branded GA.
Tolerability and safety of dimethyl fumarate in relapsing multiple sclerosis: a prospective observational multicenter study in a real-life Spanish population. [2021]Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population.
Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis. [2022]Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action. Early treatment with GA delays the onset of clinically definite MS more effectively than late treatment in clinically isolated syndrome. GA is not associated with immunosuppression, autoimmune disease, infections or development of neutralizing antibodies. A new three-times-weekly formulation of GA is available to potentially reduce the incidence of injection-related side effects. Other safety advantages of GA include its pregnancy rating (Category B) and limited uncontrolled data suggesting that tolerability is similar in children with MS.
Dimethyl Fumarate Treatment Mediates an Anti-Inflammatory Shift in B Cell Subsets of Patients with Multiple Sclerosis. [2022]The therapeutic mode of action of dimethyl fumarate (DMF), approved for treating patients with relapsing-remitting multiple sclerosis, is not fully understood. Recently, we and others demonstrated that Ab-independent functions of distinct B cell subsets are important in mediating multiple sclerosis (MS) relapsing disease activity. Our objective was to test whether and how DMF influences both the phenotype and functional responses of disease-implicated B cell subsets in patients with MS. High-quality PBMC were obtained from relapsing-remitting MS patients prior to and serially after initiation of DMF treatment. Multiparametric flow cytometry was used to monitor the phenotype and functional response-profiles of distinct B cell subsets. Total B cell counts decreased following DMF treatment, largely reflecting losses of circulating mature/differentiated (but not of immature transitional) B cells. Within the mature B cell pool, DMF had a greater impact on memory than naive B cells. In keeping with these in vivo effects, DMF treatment in vitro remarkably diminished mature (but not transitional B cell) survival, mediated by inducing apoptotic cell death. Although DMF treatment (both in vivo and in vitro) minimally impacted B cell IL-10 expression, it strongly reduced B cell expression of GM-CSF, IL-6, and TNF-α, resulting in a significant anti-inflammatory shift of B cell response profiles. The DMF-mediated decrease in B cell proinflammatory cytokine responses was further associated with reduced phosphorylation of STAT5/6 and NF-κB in surviving B cells. Together, these data implicate novel mechanisms by which DMF may modulate MS disease activity through shifting the balance between pro- and anti-inflammatory B cell responses.
Dimethyl fumarate as a first- vs second-line therapy in MS: Focus on B cells. [2022]To elucidate the immunomodulatory effects of dimethyl fumarate (DMF) on B cells in patients with relapsing MS receiving DMF as a "1st-line" vs "2nd-line" therapy.
Interferon-β treatment normalises the inhibitory effect of serum from multiple sclerosis patients on oligodendrocyte progenitor proliferation. [2010]Interferon-beta (IFN-β) is an established therapy for relapsing-remitting multiple sclerosis (MS). However, the mode of action and the effect on oligodendrocytes are not yet clear. In this study, we examined the influence of an IFN-β therapy on the proliferation and differentiation of primary oligodendrocyte precursor cells (OPC) in mixed glial cultures. Mixed glial cultures were incubated for 5 days in medium supplemented with 10% of sera from healthy controls, untreated MS patients and IFN-β treated MS patients. Proliferation and differentiation of OPC were determined by immunocytochemistry. Proliferation of OPC was significantly inhibited by sera from untreated MS patients compared to healthy controls, while this effect was almost completely reversed by serum from IFN-β treated MS patients. No effect on OPC differentiation was observed. A prospective and longitudinal analysis of a second cohort of MS patients treated with IFN-β showed that the reversal of inhibition of OPC proliferation was evident after 12 months of treatment but not during the first 6 months. Thus, our results suggest that IFN-β treatment has the capacity to revert the inhibitory effect of serum from MS patients on OPC proliferation. It is currently not clear what this means for regenerative processes.
A retrospective analysis of changes in lymphocyte levels in patients with multiple sclerosis during and after Tecfidera® treatment. [2022]There are currently no best practice recommendations for lymphocyte subset monitoring for patients with multiple sclerosis (pwMS) on disease-modifying therapies including Tecfidera® (dimethyl fumarate, DMF). However, there have been several cases of pwMS on DMF without severe lymphopenia who had high CD4:CD8 T cell ratios and went on to develop progressive multifocal leukoencephalopathy.
Single-Cell Transcriptome Profiling Unravels Distinct Peripheral Blood Immune Cell Signatures of RRMS and MOG Antibody-Associated Disease. [2022]Relapsing-remitting multiple sclerosis (RRMS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) are inflammatory demyelinating diseases of the central nervous system (CNS). Due to the shared clinical manifestations, detection of disease-specific serum antibody of the two diseases is currently considered as the gold standard for the diagnosis; however, the serum antibody levels are unpredictable during different stages of the two diseases. Herein, peripheral blood single-cell transcriptome was used to unveil distinct immune cell signatures of the two diseases, with the aim to provide predictive discrimination. Single-cell RNA sequencing (scRNA-seq) was conducted on the peripheral blood from three subjects, i.e., one patient with RRMS, one patient with MOGAD, and one patient with healthy control. The results showed that the CD19+ CXCR4+ naive B cell subsets were significantly expanded in both RRMS and MOGAD, which was verified by flow cytometry. More importantly, RRMS single-cell transcriptomic was characterized by increased naive CD8+ T cells and cytotoxic memory-like Natural Killer (NK) cells, together with decreased inflammatory monocytes, whereas MOGAD exhibited increased inflammatory monocytes and cytotoxic CD8 effector T cells, coupled with decreased plasma cells and memory B cells. Collectively, our findings indicate that the two diseases exhibit distinct immune cell signatures, which allows for highly predictive discrimination of the two diseases and paves a novel avenue for diagnosis and therapy of neuroinflammatory diseases.