Regulatory T Cells for ALS
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Novabio Therapeutics
Must be taking: Riluzole, Edaravone
Must not be taking: Antipsychotics, Antiepileptics, Antiarrhythmics
Disqualifiers: Uncontrolled infection, Hypertension, Cardiology, others
No Placebo Group
Trial Summary
What is the purpose of this trial?An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection (NP001 cell injection) in patients with Neurodegenerative diseases (ALS, MSA, AD).
Do I need to stop taking my current medications for this trial?
The trial does not specify if you need to stop taking your current medications, but it mentions that patients with ALS can continue treatment with riluzole and/or edaravone. It also excludes those currently using certain medications like antipsychotics and some antiarrhythmic drugs.
What data supports the effectiveness of the treatment Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection) for ALS?
Research shows that using regulatory T cells (a type of immune cell) in ALS patients can be safe and may help stabilize the disease. These cells have been shown to increase in number and improve their function, which might slow down the progression of ALS.
12345Is the treatment with regulatory T cells safe for humans?
Studies show that treatments using regulatory T cells, including NP001, are generally safe and well tolerated in humans, including those with ALS. These treatments have been tested in early-stage trials and have shown no major safety concerns.
12346How is the treatment using Autologous Human Polyclonal Regulatory T Cells Injection different from other ALS treatments?
This treatment is unique because it uses the patient's own regulatory T cells, which are expanded and reintroduced to help modulate the immune system and potentially slow disease progression, unlike traditional ALS treatments that do not focus on immune regulation.
12345Eligibility Criteria
This trial is for individuals with neurodegenerative diseases like ALS, Alzheimer's, and Multiple System Atrophy. Participants must have a confirmed diagnosis and be in stable condition to receive T cell injections.Inclusion Criteria
Specific laboratory values within normal ranges
I can walk by myself, expected to live 3+ years, and think clearly.
I am 65 or older with Alzheimer's, on stable medication, and can consent.
+7 more
Exclusion Criteria
I have had a pulmonary embolism in the last 6 months.
I am currently taking certain medications.
Seropositive for HIV, hepatitis B, or hepatitis C
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Apheresis and Manufacturing
Apheresis procedure to collect cells for manufacturing the investigational product, NP001 cell injection
2-4 weeks
Treatment
Participants receive NP001 cell injection intrathecally on Days 1, 29, and 57
8 weeks
3 visits (in-person)
Follow-up
Participants are monitored for safety and efficacy parameters
10 months
Participant Groups
The study tests the safety and potential benefits of injecting patients' own regulatory T cells (NP001 cell injection) to treat various neurodegenerative conditions.
1Treatment groups
Experimental Treatment
Group I: Autologous Human Polyclonal Regulatory T Cells Injection (NP001 Cell Injection)Experimental Treatment1 Intervention
Regulatory T cell therapy, intrathecal injection
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ascension Via Christi ClinicWichita, KS
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Who Is Running the Clinical Trial?
Novabio TherapeuticsLead Sponsor
The First Affiliated Hospital of Zhengzhou UniversityCollaborator
References
Expanded autologous regulatory T-lymphocyte infusions in ALS: A phase I, first-in-human study. [2022]To determine whether autologous infusions of expanded regulatory T lymphoctyes (Tregs) into patients with amyotrophic lateral sclerosis (ALS) are safe and tolerable during early and later stages of disease.
Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis. [2022]In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results.
A robust, good manufacturing practice-compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy. [2022]Regulatory T cells (Tregs) play a fundamental role in the maintenance of self-tolerance and immune homeostasis. Defects in Treg function and/or frequencies have been reported in multiple disease models. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Compelling evidence supports a neuroprotective role for Tregs in this disease. Indeed, rapid progression in ALS patients is associated with decreased FoxP3 expression and Treg frequencies. Thus, we propose that strategies to restore Treg number and function may slow disease progression in ALS. In this study, we developed a robust, Good Manufacturing Practice (GMP)-compliant procedure to enrich and expand Tregs from ALS patients. Tregs isolated from these patients were phenotypically similar to those from healthy individuals but were impaired in their ability to suppress T-cell effector function. In vitro expansion of Tregs for 4 weeks in the presence of GMP-grade anti-CD3/CD28 beads, interleukin (IL)-2 and rapamcyin resulted in a 25- to 200-fold increase in their number and restored their immunoregulatory activity. Collectively, our data facilitate and support the implementation of clinical trials of adoptive therapy with ex vivo expanded and highly suppressive Tregs in patients with ALS.
Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation. [2023]Amyotrophic lateral sclerosis (ALS) is a fatal disease associated with motor neuron degeneration, accumulation of aggregated misfolded proteins and neuroinflammation in motor regions of the central nervous system (CNS). Clinical trials using regulatory T cells (Tregs) are ongoing because of Tregs' immunomodulatory function, ability to traffic to the CNS, high numbers correlating with slower disease in ALS and disease-modifying activity in ALS mouse models. In the current study, a chimeric antigen receptor (CAR) was developed and characterized in human Tregs to enhance their immunomodulatory activity when in contact with an ALS protein aggregate.
CD4+ regulatory T cells are spared from deletion by antilymphocyte serum, a polyclonal anti-T cell antibody. [2019]Broad T cell depletion has been used as an integral part of treatment in transplantation and autoimmune diseases. Following depletion, residual T cells undergo homeostatic proliferation and convert to memory-like T cells. In this study, we investigated the effect of T cell depletion by antilymphocyte serum (ALS), a polyclonal anti-T cell Ab, on CD4(+) regulatory T cells. After ALS treatment, CD4(+)CD25(+) T cells underwent proliferation and expressed a memory T cell marker, CD44. One week after ALS treatment, both CD25(+) and CD25(-) T cells exhibited increased suppression of alloresponses in vitro, which waned thereafter to the levels mediated by naive CD25(+) and CD25(-) T cells. By real-time PCR analyses, ALS treatment of CD4-deficient mice adoptively transferred with Thy1.2(+)CD4(+)CD25(+)Foxp3(+) and Thy1.1(+)CD4(+)CD25(-)Foxp3(-) T cells resulted in the appearance of Thy1.2(+)CD4(+)CD25(-)Foxp3(+) and Thy1.1(+)CD4(+)CD25(+)Foxp3(+) T cells, suggesting the conversion between CD25(+) and CD25(-) T cells. Naive CD25(+) T cells expressed a higher level of intracellular Bcl-x(L) than CD25(-) T cells. Up-regulation of the Bcl-x(L) molecule during ALS-induced homeostatic expansion further promoted survival of CD25(+) and, to a lessor degree, CD25(-) cells. These results indicate that CD25(+) T cells are spared from ALS-mediated deletion, with some CD25(+) T cells converting to CD25(-) T cells, and continue to exhibit regulatory activity. The concomitant presence of T cell deletion and continuous regulatory T cell activity may underlie the therapeutic effect of ALS, particularly in treatment of autoimmune diseases.
NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study. [2021]This is a phase I, placebo-controlled, single ascending dose safety and tolerability study of NP001 in patients with ALS. NP001 is a novel regulator of inflammatory macrophages and monocytes. As ALS progression is thought to be related to neuroinflammation, an additional objective of the study was to assess the effects of NP001 administration on monocyte activation markers. Thirty-two ALS patients were enrolled and received either placebo (eight) or one of four (six at each dose) ascending single i.v. doses (0.2, 0.8, 1.6 and 3.2 mg/kg NP001). Patients were monitored for safety, and blood monocyte immune activation markers CD16 and HLA-DR were assessed pre- and 24 h post-dosing. Changes from baseline were calculated. Results showed that NP001 was generally safe and well tolerated. Importantly, a single dose of NP001 caused a dose-dependent reduction in expression of monocyte CD16, a marker of monocyte activation/inflammation. Additionally, monocyte HLA-DR expression was also decreased in those patients with elevated values at baseline. In conclusion, these data indicate that NP001 has an acute effect on inflammatory monocytes in ALS patient blood. The potential for modulation of inflammation in the context of ALS disease progression will require further study with long-term follow-up.