Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

Ozlem Altay; Muhammad Arif; Xiangyu Li; Hong Yang; Mehtap Aydın; Gizem Alkurt; Woonghee Kim; Dogukan Akyol; Cheng Zhang; Gizem Dinler-Doganay; Hasan Turkez; Saeed Shoaie; Jens Nielsen; Jan Borén; Oktay Olmuscelik; Levent Doganay; Mathias Uhlén; Adil Mardinoglu

doi:10.1002/advs.202101222

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

Ozlem Altay
, Muhammad Arif
, Xiangyu Li
, Hong Yang
, Mehtap Aydın
, Gizem Alkurt
, Woonghee Kim
, Dogukan Akyol
, Cheng Zhang
, Gizem Dinler-Doganay
, Hasan Turkez
, Saeed Shoaie
, Jens Nielsen
, Jan Borén
, Oktay Olmuscelik
, Levent Doganay
, Mathias Uhlén
, Adil Mardinoglu^*

^*Bu çalışma için yazışmadan sorumlu yazar

Mol.Biyoloji ve Genetik Bölümü

KTH Royal Institute of Technology
University of Health Sciences
Zhengzhou University
Ataturk University
King's College London
Chalmers University of Technology
Sahlgrenska University Hospital
Istanbul Medipol University

Araştırma çıktısı: Dergi yayını › Makale › Hakem

69 Atıf (Scopus)

Özet

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD⁺) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

Orijinal dil	İngilizce
Makale numarası	2101222
Dergi	Advanced Science
Hacim	8
Basın numarası	17
DOI'lar	https://doi.org/10.1002/advs.202101222
Yayın durumu	Yayınlandı - 8 Eyl 2021

Bibliyografik not

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Finansman

O.A., M.A., and X.L. contributed equally to this work. This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation. The authors would like to thank the Plasma Profiling Facility team at SciLifeLab in Stockholm for generating the Olink data, Metabolon Inc. (Durham, USA) for generating the metabolomics data, and ChromaDex Inc. (Irvine, CA, USA) for providing NR. A.M. and H.Y. acknowledge support from the PoLiMeR Innovative Training Network (Marie Skłodowska-Curie Grant Agreement No. 812616) which has received funding from the European Union's Horizon 2020 research and innovation programme. O.A., M.A., and X.L. contributed equally to this work. This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation. The authors would like to thank the Plasma Profiling Facility team at SciLifeLab in Stockholm for generating the Olink data, Metabolon Inc. (Durham, USA) for generating the metabolomics data, and ChromaDex Inc. (Irvine, CA, USA) for providing NR. A.M. and H.Y. acknowledge support from the PoLiMeR Innovative Training Network (Marie Skłodowska‐Curie Grant Agreement No. 812616) which has received funding from the European Union's Horizon 2020 research and innovation programme.

Finansörler	Finansör numarası
ChromaDex Inc.
Metabolon Inc.
Plasma Profiling Facility team at SciLifeLab
PoLiMeR Innovative Training Network
ScandiBio Therapeutics
H2020 Marie Skłodowska-Curie Actions	812616
Knut och Alice Wallenbergs Stiftelse
Horizon 2020

BM SKH

Bu sonuç, aşağıdaki Sürdürülebilir Kalkınma Hedefine/Hedeflerine katkıda bulunur

SKH 3 Sağlık ve Kaliteli Yaşam

Belgeye Erişim

10.1002/advs.202101222

Diğer Dosyalar ve Linkler

Link to publication in Scopus

Alıntı Yap

Altay, O., Arif, M., Li, X., Yang, H., Aydın, M., Alkurt, G., Kim, W., Akyol, D., Zhang, C., Dinler-Doganay, G., Turkez, H., Shoaie, S., Nielsen, J., Borén, J., Olmuscelik, O., Doganay, L., Uhlén, M., & Mardinoglu, A. (2021). Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19. Advanced Science, 8(17), Makale 2101222. https://doi.org/10.1002/advs.202101222

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title = "Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19",

abstract = "COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.",

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author = "Ozlem Altay and Muhammad Arif and Xiangyu Li and Hong Yang and Mehtap Aydın and Gizem Alkurt and Woonghee Kim and Dogukan Akyol and Cheng Zhang and Gizem Dinler-Doganay and Hasan Turkez and Saeed Shoaie and Jens Nielsen and Jan Bor{\'e}n and Oktay Olmuscelik and Levent Doganay and Mathias Uhl{\'e}n and Adil Mardinoglu",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",

year = "2021",

month = sep,

day = "8",

doi = "10.1002/advs.202101222",

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Altay, O, Arif, M, Li, X, Yang, H, Aydın, M, Alkurt, G, Kim, W, Akyol, D, Zhang, C, Dinler-Doganay, G, Turkez, H, Shoaie, S, Nielsen, J, Borén, J, Olmuscelik, O, Doganay, L, Uhlén, M & Mardinoglu, A 2021, 'Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19', Advanced Science, hac. 8, no. 17, 2101222. https://doi.org/10.1002/advs.202101222

TY - JOUR

T1 - Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

AU - Altay, Ozlem

AU - Arif, Muhammad

AU - Li, Xiangyu

AU - Yang, Hong

AU - Aydın, Mehtap

AU - Alkurt, Gizem

AU - Kim, Woonghee

AU - Akyol, Dogukan

AU - Zhang, Cheng

AU - Dinler-Doganay, Gizem

AU - Turkez, Hasan

AU - Shoaie, Saeed

AU - Nielsen, Jens

AU - Borén, Jan

AU - Olmuscelik, Oktay

AU - Doganay, Levent

AU - Uhlén, Mathias

AU - Mardinoglu, Adil

PY - 2021/9/8

Y1 - 2021/9/8

N2 - COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

AB - COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

KW - COVID-19

KW - combined metabolic activators

KW - metabolomics

KW - omics data

KW - proteomics

UR - https://www.scopus.com/pages/publications/85108981325

U2 - 10.1002/advs.202101222

DO - 10.1002/advs.202101222

M3 - Article

C2 - 34180141

AN - SCOPUS:85108981325

SN - 2198-3844

VL - 8

JO - Advanced Science

JF - Advanced Science

IS - 17

M1 - 2101222

ER -

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

Özet

Bibliyografik not

Finansman

BM SKH

Belgeye Erişim

Diğer Dosyalar ve Linkler

Parmak izi

Alıntı Yap