Does TUDCA treat ALS (amyotrophic lateral sclerosis)?

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TUDCA has been investigated as a potential treatment for amyotrophic lateral sclerosis (ALS, also known as motor neuron disease or Lou Gehrig's disease). While TUDCA appears safe and showed potential in earlier studies, robust evidence from large randomized controlled trials does not support its efficacy in treating ALS. Further research is needed to clarify its role, if any, in managing the disease. An overview of the current evidence is provided below.

A preliminary study in 2015 suggested that TUDCA might slow disease progression, as measured by improvements in the ALS Functional Rating Scale-Revised (ALSFRS-R).[1] These findings led to the off-label prescription of TUDCA in Italy's Emilia Romagna Region for ALS patients,[2] and a retrospective analysis of the ALS registry in that region of Italy suggested that TUDCA, at dosages up to 1,000 mg/day, might improve survival in patients with ALS compared to patients receiving standard care.[3] However, despite these promising early results, the large-scale Phase 3 randomized controlled trial TUDCA-ALS found no significant benefit of TUDCA in reducing ALS progression.[4][5][6][7]

Similarly, early preliminary studies of a combination therapy for ALS showed promise.[8][9][10] The drug used in these studies was called Relyvrio, or AMX0035, and contains sodium phenylbutyrate and taurursodiol (taurursodiol is another name for TUDCA). However, the PHOENIX study, a large-scale Phase 3 trial, found no significant benefit of Relyvrio in reducing ALS progression.[11][12] Subsequently, Relyvrio was withdrawn from the US and Canadian markets in 2024.[13]

References
1.^Elia AE, Lalli S, Monsurrò MR, Sagnelli A, Taiello AC, Reggiori B, La Bella V, Tedeschi G, Albanese ATauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.Eur J Neurol.(2016 Jan)
2.^Mandrioli J, Biguzzi S, Guidi C, Venturini E, Sette E, Terlizzi E, Ravasio A, Casmiro M, Salvi F, Liguori R, Rizzi R, Pietrini V, Chierici E, Santangelo M, Granieri E, Mussuto V, Borghi A, Rinaldi R, Fini N, Georgoulopoulou E, De Pasqua S, Vinceti M, Bonvicini F, Errals Group, Ferro S, D'Alessandro REpidemiology of amyotrophic lateral sclerosis in Emilia Romagna Region (Italy): A population based study.Amyotroph Lateral Scler Frontotemporal Degener.(2014 Jun)
3.^Zucchi E, Musazzi UM, Fedele G, Martinelli I, Gianferrari G, Simonini C, Fini N, Ghezzi A, Caputo M, Sette E, Vacchiano V, Zinno L, Anceschi P, Canali E, Vinceti M, Ferro S, Mandrioli J, ERRALS study groupEffect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study.EClinicalMedicine.(2023 Nov)
5.^Albanese A, Ludolph AC, McDermott CJ, Corcia P, Van Damme P, Van den Berg LH, Hardiman O, Rinaldi G, Vanacore N, Dickie B, TUDCA-ALS Study GroupTauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis: The TUDCA-ALS trial protocol.Front Neurol.(2022)
6.^Lombardo FL, Spila Alegiani S, Mayer F, Cipriani M, Lo Giudice M, Ludolph AC, McDermott CJ, Corcia P, Van Damme P, Van den Berg LH, Hardiman O, Nicolini G, Vanacore N, Dickie B, Albanese A, Puopolo M, TUDCA-ALS Study GroupA randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial.Trials.(2023 Dec 5)
8.^Paganoni S, Macklin EA, Hendrix S, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson T, Jackson CE, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha S, Miller TM, Scelsa SN, Vu TH, Fournier CN, Glass JD, Johnson KM, Swenson A, Goyal NA, Pattee GL, Andres PL, Babu S, Chase M, Dagostino D, Dickson SP, Ellison N, Hall M, Hendrix K, Kittle G, McGovern M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Walker J, Yu H, Chan J, Wittes J, Cohen J, Klee J, Leslie K, Tanzi RE, Gilbert W, Yeramian PD, Schoenfeld D, Cudkowicz METrial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.N Engl J Med.(2020 Sep 3)
9.^Paganoni S, Hendrix S, Dickson SP, Knowlton N, Macklin EA, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson CE, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha S, Miller TM, Scelsa SN, Vu TH, Fournier CN, Glass JD, Johnson KM, Swenson A, Goyal NA, Pattee GL, Andres PL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, McGovern M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, St Pierre ME, Tustison E, Vigneswaran P, Walker J, Yu H, Chan J, Wittes J, Yu ZF, Cohen J, Klee J, Leslie K, Tanzi RE, Gilbert W, Yeramian PD, Schoenfeld D, Cudkowicz MELong-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.Muscle Nerve.(2021 Jan)
10.^Paganoni S, Hendrix S, Dickson SP, Knowlton N, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson C, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha SS, Miller TM, Scelsa SN, Vu TH, Fournier C, Johnson KM, Swenson A, Goyal N, Pattee GL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Yu H, Cohen J, Klee J, Tanzi R, Gilbert W, Yeramian P, Cudkowicz MEffect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial.J Neurol Neurosurg Psychiatry.(2022 May 16)