Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

J Mandrioli; R D'Amico; E Zucchi; A Gessani; N Fini; A Fasano; C Caponnetto; A Chiò; E Dalla Bella; C Lunetta; L Mazzini; K Marinou; G Sorarù; S De Biasi; D Lo Tartaro; M Pinti; P Nichelli; R Vicini; C Cabona; A Calvo; C Moglia; U Manera; G Fuda; A Canosa; A Ilardi; G Lauria; Bella E Dalla; F Gerardi; A Scognamiglio; Fabiola DE MARCHI; G Mora; M Gizzi; A Cossarizza

doi:10.1097/MD.0000000000011119

Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

J Mandrioli, R D'Amico, E Zucchi, A Gessani, N Fini, A Fasano, C Caponnetto, A Chiò, E Dalla Bella, C Lunetta, L Mazzini, K Marinou, G Sorarù, S De Biasi, D Lo Tartaro, M Pinti, P Nichelli, R Vicini, C Cabona, A CalvoC Moglia, U Manera, G Fuda, A Canosa, A Ilardi, G Lauria, Bella E Dalla, F Gerardi, A Scognamiglio, Fabiola DE MARCHI, G Mora, M Gizzi, A Cossarizza

Dipartimento di Medicina Traslazionale

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients.

Lingua originale	Inglese
Rivista	MEDICINE
Volume	97
Numero di pubblicazione	24
DOI	https://doi.org/10.1097/MD.0000000000011119
Stato di pubblicazione	Pubblicato - 2018

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10.1097/MD.0000000000011119

https://hdl.handle.net/11579/147501

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Mandrioli, J., D'Amico, R., Zucchi, E., Gessani, A., Fini, N., Fasano, A., Caponnetto, C., Chiò, A., Dalla Bella, E., Lunetta, C., Mazzini, L., Marinou, K., Sorarù, G., De Biasi, S., Lo Tartaro, D., Pinti, M., Nichelli, P., Vicini, R., Cabona, C., ... Cossarizza, A. (2018). Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial). MEDICINE, 97(24). https://doi.org/10.1097/MD.0000000000011119

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title = "Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)",

abstract = "Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients.",

author = "J Mandrioli and R D'Amico and E Zucchi and A Gessani and N Fini and A Fasano and C Caponnetto and A Chi{\`o} and {Dalla Bella}, E and C Lunetta and L Mazzini and K Marinou and G Sorar{\`u} and {De Biasi}, S and {Lo Tartaro}, D and M Pinti and P Nichelli and R Vicini and C Cabona and A Calvo and C Moglia and U Manera and G Fuda and A Canosa and A Ilardi and G Lauria and Dalla, {Bella E} and F Gerardi and A Scognamiglio and {DE MARCHI}, Fabiola and G Mora and M Gizzi and A Cossarizza",

note = "Publisher Copyright: {\textcopyright} 2018 the Author(s). Published by Wolters Kluwer Health, Inc.",

year = "2018",

doi = "10.1097/MD.0000000000011119",

language = "English",

volume = "97",

journal = "MEDICINE",

issn = "1536-5964",

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Mandrioli, J, D'Amico, R, Zucchi, E, Gessani, A, Fini, N, Fasano, A, Caponnetto, C, Chiò, A, Dalla Bella, E, Lunetta, C, Mazzini, L, Marinou, K, Sorarù, G, De Biasi, S, Lo Tartaro, D, Pinti, M, Nichelli, P, Vicini, R, Cabona, C, Calvo, A, Moglia, C, Manera, U, Fuda, G, Canosa, A, Ilardi, A, Lauria, G, Dalla, BE, Gerardi, F, Scognamiglio, A, DE MARCHI, F, Mora, G, Gizzi, M & Cossarizza, A 2018, 'Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)', MEDICINE, vol. 97, n. 24. https://doi.org/10.1097/MD.0000000000011119

TY - JOUR

T1 - Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

AU - Mandrioli, J

AU - D'Amico, R

AU - Zucchi, E

AU - Gessani, A

AU - Fini, N

AU - Fasano, A

AU - Caponnetto, C

AU - Chiò, A

AU - Dalla Bella, E

AU - Lunetta, C

AU - Mazzini, L

AU - Marinou, K

AU - Sorarù, G

AU - De Biasi, S

AU - Lo Tartaro, D

AU - Pinti, M

AU - Nichelli, P

AU - Vicini, R

AU - Cabona, C

AU - Calvo, A

AU - Moglia, C

AU - Manera, U

AU - Fuda, G

AU - Canosa, A

AU - Ilardi, A

AU - Lauria, G

AU - Dalla, Bella E

AU - Gerardi, F

AU - Scognamiglio, A

AU - DE MARCHI, Fabiola

AU - Mora, G

AU - Gizzi, M

AU - Cossarizza, A

PY - 2018

Y1 - 2018

N2 - Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients.

AB - Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients.

UR - https://iris.uniupo.it/handle/11579/147501

U2 - 10.1097/MD.0000000000011119

DO - 10.1097/MD.0000000000011119

M3 - Article

SN - 1536-5964

VL - 97

JO - MEDICINE

JF - MEDICINE

IS - 24

ER -

Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial)

Abstract

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