MSC Therapy for Asthma

Overseen By Anne Fitzpatrick, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Corticosteroids, Macrolides, Anticonvulsants, others

Disqualifiers: Chronic lung disease, Smoking, Diabetes, others

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

Compensation: Varies

Number of Visits: 14

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with moderate-to-severe asthma that began in childhood. Researchers are studying two types of stem cell-based therapies to assess their safety and determine the optimal dose. Participants will receive an infusion of interferon gamma-primed mesenchymal stromal cells, which are special cells that can help reduce inflammation. The trial seeks individuals with persistent asthma symptoms and allergies, such as hay fever or allergic reactions. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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

The trial requires that you stop using oral or injectable corticosteroids and certain other medications that interact with corticosteroids at least two weeks before the screening visit. Nasal corticosteroids can be used during the trial, and you should not start new asthma therapies until 7 days after the γMSC infusion.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that certain cells, called mesenchymal stromal cells (MSCs), might help treat diseases related to the immune system. These cells can reduce inflammation and repair the immune system. In animal studies, MSCs have been safe and did not cause serious side effects.

When prepared with a protein called interferon-gamma, which aids the immune system, MSCs might work even better. However, this specific treatment has not been extensively tested in people yet. Since this trial is in its early stages, the main goal is to ensure the treatment's safety. While past research is promising, this trial is crucial to assess the safety of these cells for children with severe asthma.

Participation in this study will help researchers learn more about the treatment's safety. This trial is an important step in determining if these special cells can be a safe option for treating asthma in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using interferon gamma-primed mesenchymal stromal cells (γMSCs) for asthma because this approach is quite different from current treatments like inhaled corticosteroids and bronchodilators. Unlike these standard options, which primarily focus on reducing inflammation or relaxing airway muscles, γMSCs have the potential to modify the body's immune response. By using interferon gamma to prime the cells, the treatment may boost their ability to repair lung tissue and reduce chronic inflammation in a more targeted way. This novel mechanism of action could offer a new avenue for managing asthma, especially for patients who don't respond well to existing medications.

What evidence suggests that this treatment might be an effective treatment for asthma?

Research suggests that a special type of cell, called γMSCs, might help treat asthma by reducing airway inflammation and correcting immune system issues. Lab studies have shown promise for these cells, as they were tested in controlled environments before human trials. In this trial, participants will receive an infusion of γMSCs at either a low or high dose. Researchers believe γMSCs help the body reduce inflammation, a major problem in asthma, and aid in repairing damaged tissues by encouraging healthy cell growth. While more research is needed to confirm these benefits in people, early results are encouraging. ^{2 3 4 5 6}

Who Is on the Research Team?

Edwin Horwitz, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-30 with moderate-to-severe persistent asthma diagnosed in childhood and evidence of atopy. Participants must not have other chronic lung diseases, be on new biologic asthma therapies, or have used oral/injectable corticosteroids within two weeks prior to screening. Women must use birth control if applicable.

Inclusion Criteria

My asthma started when I was a child.

I have moderate-to-severe asthma.

I have been diagnosed with asthma by a doctor.

Exclusion Criteria

I have been on a stable allergy shot regimen for at least 3 months.

I haven't taken drugs like carbamazepine or erythromycin in the last two weeks.

I have a history of eye issues or conditions worsened by steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single intravenous infusion of γMSCs at either 2x10^6 cells/kg or 5x10^6 cells/kg

1 day

1 visit (in-person)

Observation

Participants are observed for adverse reactions and safety assessments post-infusion

7 to 30 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including lung function tests and analysis of inflammatory markers

1 year

Up to 12 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Interferon gamma-primed mesenchymal stromal cells (MSCs)

Trial Overview The study tests the safety and optimal dose of two types of mesenchymal stromal cells (MSCs) treatments: one derived from cord tissue (cMSCs), another primed with interferon gamma from bone marrow (γMSCs). It's a Phase I trial with children receiving escalating doses to assess tolerance.

How Is the Trial Designed?

Group I: Infusion of γMSCs Experimental Treatment 3 Interventions

Escalating doses Dose escalation design with two dose levels. The low dose level involves a single intravenous infusion of γMSCs at 2x106 cells/kg. The high dose level involves a single intravenous infusion of γMSCs at 5x106 cells/kg.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

Ossium Health, Inc.

Industry Sponsor

Trials

11

Recruited

200+

Published Research Related to This Trial

Interferon (IFN)-alpha significantly reduced eosinophil recruitment and improved airway hyperresponsiveness in a guinea pig model of asthma, suggesting its potential efficacy in treating severe asthma.

IFN-alpha modulates the expression of adhesion molecules, specifically inhibiting ICAM-1 on endothelial cells, which may help control chronic airway inflammation in asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-alpha inhibits airway eosinophilia and hyperresponsiveness in an animal asthma model [corrected]. Kikkawa, Y., Sugiyama, K., Obara, K., et al.[2021]

Inhaled IFN-λ significantly reduces Th2 and Th17 inflammation in the lungs of asthmatic mice, suggesting its potential as a therapeutic option for controlling allergic asthma.

The treatment not only improved lung histopathology and normalized lung resistance but also increased IL-10 secretion, indicating a regulatory effect on inflammation even after asthma has developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled delivery of recombinant interferon-lambda restores allergic inflammation after development of asthma by controlling Th2- and Th17-cell-mediated immune responses. Won, J., Jo, A., Gil, CH., et al.[2023]

In a study of 2793 adults with severe asthma, long-term maintenance systemic corticosteroid (mSCS) therapy was linked to a high prevalence of adverse effects, including adrenal insufficiency, pneumonia, and type 2 diabetes.

Patients using mSCS for 2 years or more faced even greater risks, such as osteoporosis and coronary artery disease, highlighting the need for healthcare professionals to consider mSCS-sparing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Use of Maintenance Systemic Corticosteroids is Associated with Multiple Adverse Conditions in a Large, Real-World Cohort of US Adults with Severe Asthma. Lugogo, N., Chipps, BE., Panettieri, RA., et al.[2022]

In a study involving asthmatic mice, treatment with recombinant IFN-λ2/3 significantly reduced Th2-related cytokines (TSLP and IL-33) and improved lung inflammation, suggesting its potential as a therapeutic intervention for asthma.

The administration of IFN-λ2/3 not only normalized lung resistance but also correlated with increased expression of IFN-stimulated genes, indicating a mechanism by which IFN-λs can modulate immune responses in allergic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled delivery of Interferon-lambda restricts epithelial-derived Th2 inflammation in allergic asthma. Won, J., Gil, CH., Jo, A., et al.[2020]

Mucosal IFN-gamma gene transfer in a mouse model of allergic asthma significantly increases IFN-gamma expression in the lungs, which is crucial for combating airway inflammation.

This gene transfer method effectively reduces both eosinophilia and airway hyperreactivity caused by allergens and Th2 cells, indicating its potential as a novel therapy for allergic asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal IFN-gamma gene transfer inhibits pulmonary allergic responses in mice. Li, XM., Chopra, RK., Chou, TY., et al.[2008]

Low doses of exogenous interferon (IFN)-γ significantly reduced airway inflammation in an asthma model by decreasing inflammatory cell infiltration and Th2 cytokine production, as shown in a study with 42 mice.

The mechanism involves enhancing Fas/FasL-induced apoptosis in CD4(+) T cells, indicating that low doses of IFN-γ can effectively modulate immune responses in asthma without disrupting the Th1/Th2 balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low doses of exogenous interferon-γ attenuated airway inflammation through enhancing Fas/FasL-induced CD4+ T cell apoptosis in a mouse asthma model. Yao, Y., Lu, S., Li, H., et al.[2021]

In a double-blind study involving 30 patients with bronchial asthma, 20 injections of recombinant IFN-gamma significantly reduced skin wheal area, indicating potential anti-allergic effects.

However, IFN-gamma did not have any impact on allergic bronchoconstriction, suggesting that while it may help with skin reactions, it does not alleviate breathing difficulties associated with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of recombinant gamma interferon on allergic skin reaction and bronchoconstriction]. Scholz, D., Brandt-Höfflin, K., Hahn, HL.[2011]

Human mesenchymal stem cells (hMSCs), specifically from adipose and bone marrow sources, can effectively reduce airway hyperresponsiveness and inflammation in a mouse model of allergic asthma, indicating their potential as a therapeutic option.

However, administering hMSCs twice during the sensitization and challenge phases worsened inflammation and increased TH2 cytokine levels, suggesting that a single treatment is safer and more effective for managing asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma. Hur, J., Kang, JY., Kim, YK., et al.[2021]

Therapeutic administration of bone marrow-derived mesenchymal stromal cells (BM-MSCs) reduced eosinophil and B cell influx in the lungs of mice with house dust mite-induced asthma, indicating an anti-inflammatory effect, but did not improve lung function or airway remodeling.

While BM-MSCs can increase Treg cell numbers in unprimed lymphocytes, they do not promote Treg expansion in allergen-primed lymphocytes, suggesting that their efficacy may be limited in established inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic administration of bone marrow-derived mesenchymal stromal cells reduces airway inflammation without up-regulating Tregs in experimental asthma. Kitoko, JZ., de Castro, LL., Nascimento, AP., et al.[2019]

Transferring bone marrow-derived mesenchymal stem cells (BMDMSCs) into rats with severe asthma significantly reduced airway inflammation and remodeling, as evidenced by decreased inflammatory cell counts and collagen deposition in lung tissue.

BMDMSC treatment also normalized the airway response to methacholine, indicating improved lung function and suggesting a potential therapeutic approach for managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell transfer suppresses airway remodeling in a toluene diisocyanate-induced murine asthma model. Lee, SH., Jang, AS., Kwon, JH., et al.[2022]

Mesenchymal stem cells (MSCs) can enhance the proliferation of lymphocytes in allergic rhinitis (AR) patients, contrasting with their suppressive effects in allergic asthma, indicating that MSCs' immune functions may vary by disease type.

The study found that MSCs act as antigen-presenting cells in AR, leading to increased inflammatory cytokine production, which suggests that the inflammatory environment influences MSC behavior and highlights the need for careful consideration in therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pollen-induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis. Desai, MB., Gavrilova, T., Liu, J., et al.[2020]

In a mouse model of asthma, mesenchymal stem cells (MSCs) were found to suppress asthma symptoms by targeting lung myeloid dendritic cells (DCs), which play a key role in allergic responses.

MSCs reduced the maturation and migration of lung DCs, leading to a decreased Th2 immune response, suggesting that MSCs could be a promising therapeutic option for treating asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function. Zeng, SL., Wang, LH., Li, P., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10278440/

Mesenchymal Stem/Stromal Cells in Asthma Therapy Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical ...

2. withpower.com withpower.com/trial/phase-1-asthma-8-2021-2e277

MSC Therapy for Asthma · Info for Participants What data supports the effectiveness of the treatment Interferon gamma-primed mesenchymal stromal cells (MSCs) for asthma? Research shows that low doses of ...

3. mdpi.com mdpi.com/2227-9059/12/6/1369

Therapeutic Efficacy of Interferon-Gamma and Hypoxia ... Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9737548/

Interferon-Gamma Primed Human Clonal Mesenchymal ... We demonstrate that MSC sheets produced with IFN-γ priming upregulate expression of immunosuppressive factors indoleamine 2,3-dioxygenase (IDO-1), interleukin- ...

5. ctv.veeva.com ctv.veeva.com/study/mechanisms-of-interferon-gamma-primed-mesenchymal-stromal-cells-mscs-for-moderate-to-severe-persis

Mechanisms of Interferon Gamma-primed Mesenchymal ... This study will determine whether one form of MSCs called "interferon gamma-primed MSCs or γMSCs" are safe for patients with moderate-to-severe ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05035862

NCT05035862 | Mechanisms of Interferon Gamma-primed ... The primary objectives are to determine the safety and toxicity of allogeneic cord tissue derived MSCs and allogeneic interferon-γ primed bone marrow derived ...