MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A

Hemed-Shaked, Maayan; Cowman, Mary K.; Kim, Jin Ryoun; Huang, Xiayun; Chau, Edward; Ovadia, Haim; Amar, Keren Or; Eshkar-Sebban, Lora; Melamed, Michal L.; Lev, Libat Bar; Kedar, Eli; Armengol, Jordi; Alemany, J.; Beyth, Shaul; Okon, E; Kanduc, Darja; Elgavish, Sharona; Wallach-Dayan, Shulamit B.; Cohen, Shai; Naor, David

doi:10.1016/j.jaut.2021.102713

Cited by 8 publications

(15 citation statements)

References 53 publications

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“…Nevertheless, the treatment decreased the BLI in the therapeutic approach and increased reparation markers ( Vegfa and Tgfb1 ) in the preventive design. In this trial, there was also a decrease in plasmatic levels of SAA, as expected due to the targeting action of MTADV [ 44 ]. Similarly, in another study, MTADV showed contradictory results by reducing some inflammatory markers, such as SAA, while it increased IFN-γ in TNBS mice [ 44 ].…”

Section: Discussionsupporting

confidence: 54%

“…This method was further validated by relating the BLI to the quantification of inflammatory molecular signatures in both intestinal mucosa and systemic blood. Widely used macroscopic evaluations, a bioluminescent approach, and molecular assessments allowed us to establish the variability between and within the in vivo models in the drug testing of two different treatments, one being dexamethasone, a widely used treatment in IBD, and the other being MTADV, an experimental treatment and an inhibitor of SAA [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Response Variability to Drug Testing in Two Models of Chemically Induced Colitis

Suau

Garcia

Bernal

et al. 2023

IJMS

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The lack of knowledge regarding the pathogenesis of IBD is a challenge for the development of more effective and safer therapies. Although in vivo preclinical approaches are critical for drug testing, none of the existing models accurately reproduce human IBD. Factors that influence the intra-individual response to drugs have barely been described. With this in mind, our aim was to compare the anti-inflammatory efficacy of a new molecule (MTADV) to that of corticosteroids in TNBS and DSS-induced colitis mice of both sexes in order to clarify further the response mechanism involved and the variability between sexes. The drugs were administered preventively and therapeutically, and real-time bioluminescence was performed for the in vivo time-course colitis monitoring. Morphometric data were also collected, and colonic cytokines and acute plasma phase proteins were analyzed by qRT-PCR and ELISA, respectively—bioluminescence images correlated with inflammatory markers. In the TNBS model, dexamethasone worked better in females, while MTADV improved inflammation in males. In DSS-colitis, both therapies worked similarly. Based on the molecular profiles, interaction networks were constructed to pinpoint the drivers of therapeutic response that were highly dependent on the sex. In conclusion, our results suggest the importance of considering sex in IBD preclinical drug screening.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Response Variability to Drug Testing in Two Models of Chemically Induced Colitis

Suau

Garcia

Bernal

et al. 2023

IJMS

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“…Pentapeptide sharing between SARS-CoV-2 proteins and human immunodeficiency–related proteins was analyzed using pentapeptide as a sequence probe because a peptide grouping formed by five aa residues defines a minimal immune determinant underlying the specific interaction of an antigen with B-cell receptor (BCR) and T-cell receptor (TCR). 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 The results are displayed in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…To prove/disprove the cross-reactivity paradigm, the present study comparatively analyzed the entire SARS-CoV-2 proteome and human proteins involved in immunodeficiencies searching for common amino acid (aa) sequences. Using the pentapeptide as the basic measurement unit of antigenicity and immunogenicity, 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 sequence analyses revealed peptide commonalities that are susceptible of generating cross-reactions, thus feasibly explaining the immunosuppression associated with SARS-CoV-2 passive/active infection and its increase following repeated anti-SARS-CoV-2 vaccinations.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2-Induced Immunosuppression: A Molecular Mimicry Syndrome

Kanduc

2022

Glob Med Genet

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Background Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died following SARS-CoV-2 infection. This raises the question of the causes of the virus-induced immune immunosuppression. Searching for molecular link(s) between SARS-CoV-2 immunization and the decay of the adaptive immune responses, SARS-CoV-2 proteome was analyzed for molecular mimicry with human proteins related to immunodeficiency. The aim was to verify the possibility of cross-reactions capable of destroying the adaptive immune response triggered by SARS-CoV-2. Materials and Methods Human immunodeficiency–related proteins were collected from UniProt database and analyzed for sharing of minimal immune determinants with the SARS-CoV-2 proteome. Results Molecular mimicry and consequent potential cross-reactivity exist between SARS-CoV-2 proteome and human immunoregulatory proteins such as nuclear factor kappa B (NFKB), and variable diversity joining V(D)J recombination-activating gene (RAG). Conclusion The data (1) support molecular mimicry and the associated potential cross-reactivity as a mechanism that can underlie self-reactivity against proteins involved in B- and T-cells activation/development, and (2) suggest that the extent of the immunosuppression is dictated by the extent of the immune responses themselves. The higher the titer of the immune responses triggered by SARS-CoV-2 immunization, the more severe can be the cross-reactions against the human immunodeficiency–related proteins, the more severe the immunosuppression. Hence, SARS-CoV-2-induced immunosuppression can be defined as a molecular mimicry syndrome. Clinically, the data imply that booster doses of SARS-CoV-2 vaccines may have opposite results to those expected.

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“…It does not demonstrate anti-inflammatory activity in rats, which is consistent with the absence of SAA in this species. ( 73 , 74 ). A phase I study of Amilo-5MER was recently completed in healthy young and elderly adult volunteers (Poster Presentation at Pharmacology 2022).…”

Section: Hypothesis: Saa As a Target For Treatment Of Inflammatory Co...mentioning

confidence: 99%

Serum amyloid A—A potential therapeutic target for hyper-inflammatory syndrome associated with COVID-19

et al. 2023

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Serum amyloid-A (SAA) is associated with inflammatory disorders such as rheumatoid arthritis, Familial Mediterranean Fever, sarcoidosis, and vasculitis. There is accumulating evidence that SAA is a reliable biomarker for these autoinflammatory and rheumatic diseases and may contribute to their pathophysiology. Hyperinflammatory syndrome associated with COVID-19 is a complex interaction between infection and autoimmunity and elevation of SAA is strongly correlated with severity of the inflammation. In this review we highlight the involvement of SAA in these different inflammatory conditions, consider its potential role and discuss whether it could be a potential target for treatment of the hyperinflammatory state of COVID-19 with many potential advantages and fewer adverse effects. Additional studies linking SAA to the pathophysiology of COVID-19 hyper-inflammation and autoimmunity are needed to establish the causal relationship and the therapeutic potential of inhibitors of SAA activity.

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MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A

Cited by 8 publications

References 53 publications

Response Variability to Drug Testing in Two Models of Chemically Induced Colitis

Response Variability to Drug Testing in Two Models of Chemically Induced Colitis

SARS-CoV-2-Induced Immunosuppression: A Molecular Mimicry Syndrome

Serum amyloid A—A potential therapeutic target for hyper-inflammatory syndrome associated with COVID-19

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