Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review

Rajabinejad, Misagh; Ranjbar, Sedigheh; Hezarkhani, Leila Afshar; Salari, Farhad; Karaji, Ali Gorgin; Rezaiemanesh, Alireza

doi:10.1002/jcp.29401

Cited by 26 publications

(24 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Disease progression is associated with conversion to a neurotoxic inflammatory response dominated by type 1 microglia (M1) and dysfunctional Tregs, which can no longer suppress Th1 and Th17 lymphocytes, as well as increased levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, interferon [IFN]‐γ and tumour necrosis factor α) 11,12 . A correlation between Tregs and the rate of disease progression has been previously established in ALS and was associated with neuroprotective and neurodegenerative effects in ALS mouse models and some clinical trials, 16,18 although other clinical trials have not reported a clinic benefit despite an increase in percentage of Tregs 19 . Importantly, the loss of Tregs’ suppressive ability in patients with ALS was reported to be transient, and the ability was regained when they were expanded in a different environment 17,20 .…”

Section: Introductionmentioning

confidence: 99%

“…Dimethyl fumarate, an FDA‐approved medication used for the treatment of relapsing‐remitting multiple sclerosis, 22,23 has been shown to alter immune response towards more anti‐inflammatory subsets. Specifically, dimethyl fumarate increased the number of anti‐inflammatory CCR3 + Th2 and Treg cells, shifting the pro‐ to anti‐inflammatory ratio (Th2/Th1Th17 and Treg/Th1Th17), with a simultaneous reduction in pro‐inflammatory T cells (CD4 + IFN‐γ; CD8 + IFN‐γ), thus highlighting its potential as a neuroprotective agent 17–19 . As such, the objective of this phase 2, randomised, placebo‐controlled, multicentric, double‐blind study was to assess the efficacy and safety of dimethyl fumarate in patients with ALS.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Vucic

Henderson

Mathers

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective Neuroinflammation is an important pathogenic mechanism in amyotrophic lateral sclerosis (ALS), with regulatory T cells (Tregs) mediating a slower rate of disease progression. Dimethyl fumarate enhances Treg levels and suppresses pro‐inflammatory T cells. The present study assessed the safety and efficacy of dimethyl fumarate in ALS. Methods Phase‐2, double‐blind, placebo‐controlled randomised clinical trial recruited participants from May 1, 2018 to September 25, 2019, across six Australian sites. Participants were randomised (2:1 ratio) to dimethyl fumarate (480 mg/day) or matching placebo, completing visits at screening, baseline, weeks 12, 24 and 36. The primary efficacy endpoint was a change in Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised (ALSFRS‐R) at week 36. Secondary outcome measures included survival, neurophysiological index (NI), respiratory function, urinary neurotrophin‐receptor p75 and quality of life. Results A total of 107 participants were randomised to dimethyl fumarate (n = 72) or placebo (n = 35). ALSFRS‐R score was not significantly different at week 36 (−1.12 [−3.75 to 1.52, p = 0.41]). Dimethyl fumarate was associated with a reduced NI decline week 36 (differences in the least‐squares mean: (0.84 [−0.51 to 2.22, p = 0.22]). There were no significant differences in other secondary outcome measures. Safety profiles were comparable between groups. Interpretation Dimethyl fumarate, in combination with riluzole, was safe and well‐tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Vucic

Henderson

Mathers

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…MDSCs limit immunological responses in a variety of ways, including by suppressing effector T cells and inducing Tregs (Nagaraj et al 2013;Rajabinejad et al 2020;Rajabinejad et al 2019;Kong et al 2013). Many factors work together as a complex network to ensure the expansion, activation, and survival of MDSCs.…”

Section: Introductionmentioning

confidence: 99%

Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies

Parizi

Abdolhosseini

et al. 2021

Inflammopharmacol

View full text Add to dashboard Cite

The most fatal malignancy of the central nervous system (CNS) is glioblastoma. Brain cancer is a 'cold' tumor because of fewer immunoregulatory cells and more immunosuppressive cells. Due to the cold nature of brain cancers, conventional treatments which are used to manage glioma patients show little effectiveness. Glioma patients even showed resistance to immune checkpoint blockade (ICB) and no significant efficacy. It has been shown that myeloid-derived suppressor cells (MDSCs) account for approximately 30-50% of the tumor mass in glioma. This study aimed to review MDSC function in brain cancer, as well as possible treatments and related challenges. In brain cancer and glioma, several differences in the context of MDSCs have been reported, including disagreements about the MDSC subtype that has the most inhibitory function in the brain, or inhibitory function of regulatory B cells (Bregs). There are also serious challenges in treating glioma patients. In addition to the cold nature of glioma, there are reports of an increase in MDSCs following conventional chemotherapy treatments. As a result, targeting MDSCs in combination with other therapies, such as ICB, is essential, and recent studies with the combination therapy approach have shown promising therapeutic effects in brain cancer.

show abstract

“…Nutritional restriction, hypoxia, abnormal organelles, exogenous toxins/chemicals, and oxidative stress are all known to promote autophagy. Autophagy may thus have a role in a variety of pathophysiological conditions, including malignancy (Barbosa et al, 2019; Rajabinejad et al, 2020). There are currently two theories about the function of autophagy in cancers.…”

Section: Introductionmentioning

confidence: 99%

The roles, controversies, and combination therapies of autophagy in lung cancer

Wang

Zhou

Yang

2021

Cell Biology International

View full text Add to dashboard Cite

Lung cancer is one of the leading causes of death among men and women worldwide. The disease initially has a silent phenotype, which leads to the progression of the disease and ultimately the lack of proper response to routine treatments. Autophagy, known as an intracellular “recycle bin” for the degradation of defective proteins and molecules, is one of the mechanisms that has been considered in the context of cancer in recent years. This study aims to provide a comprehensive review of published articles on autophagy in the context of lung cancer to have a complete view of the role of autophagy in lung cancer and its possible treatments. PubMed, Scopus, and Google Scholar were searched until June 15 to find related articles. No specific search filters or restrictions were applied. The results were entered into reference management software for aggregation and management. The full text of all articles was screened and studied. In conclusion, studies on the exact function of autophagy in lung cancer are contradictory, but what can be concluded from a review of literature on lung cancer is that targeting autophagy combined with traditional routine therapies such as chemotherapy, especially in advanced stages of lung cancer, can be an effective anticancer approach.

show abstract

Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review

Cited by 26 publications

References 33 publications

Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Myeloid-derived suppressor cells (MDSCs) in brain cancer: challenges and therapeutic strategies

The roles, controversies, and combination therapies of autophagy in lung cancer

Contact Info

Product

Resources

About