Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial

Michael Neumann; Hardik Kothare; Meredith Bartlett; Oliver Roesler; Christiane Suendermann-Oeft; Abhishek Hosamath; Lakshmi Arbatti; David Pautler; David Suendermann-Oeft; Diego Cadavid; Robert H. Scannevin; Ines Hoffmann; Anil Tarachandani; Tara Haley; Shane Raines; Philip Van Damme; Pentti Tienari; Eino Solje; Manu Jokela; Angela Genge; Colleen O’Connell; Ruben P.A.van Eijk; Leonard H.van den Berg; Vikram Ramanarayanan

doi:10.1038/s41598-026-48100-6

Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial

Michael Neumann^*
, Hardik Kothare
, Meredith Bartlett
, Oliver Roesler
, Christiane Suendermann-Oeft
, Abhishek Hosamath
, Lakshmi Arbatti
, David Pautler
, David Suendermann-Oeft
, Diego Cadavid
, Robert H. Scannevin
, Ines Hoffmann
, Anil Tarachandani
, Tara Haley
, Shane Raines
, Philip Van Damme
, Pentti Tienari
, Eino Solje
, Manu Jokela
, Angela Genge

Colleen O’Connell, Ruben P.A.van Eijk, Leonard H.van den Berg, Vikram Ramanarayanan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We report on the utility of speech-based digital endpoints measured during a Phase 1b study of VRG50635 in Amyotrophic Lateral Sclerosis (ALS). Fifty-four participants with ALS were enrolled and participated in an 8-week pretreatment run-in, followed by three 8-week dosing periods and an 8-week follow-up. They completed a speech assessment every two weeks in the clinic or at home. We observed moderate to high correlations between digital measures of speech timing and articulatory motor function, and the ALS Functional Rating Scale-Revised, slow vital capacity and plasma neurofilament light chain. Furthermore, speech measures can show functional decline before the ALSFRS-R does, while also capturing differences between participants with bulbar symptoms and those without. The results support the feasibility and utility of digital speech endpoints to study disease impact in ALS clinical trials.

Original language	English
Article number	20088
Journal	Scientific Reports
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41598-026-48100-6
Publication status	Published - 2026

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Neumann, M., Kothare, H., Bartlett, M., Roesler, O., Suendermann-Oeft, C., Hosamath, A., Arbatti, L., Pautler, D., Suendermann-Oeft, D., Cadavid, D., Scannevin, R. H., Hoffmann, I., Tarachandani, A., Haley, T., Raines, S., Damme, P. V., Tienari, P., Solje, E., Jokela, M., ... Ramanarayanan, V. (2026). Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial. Scientific Reports, 16(1), Article 20088. https://doi.org/10.1038/s41598-026-48100-6

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title = "Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial",

abstract = "We report on the utility of speech-based digital endpoints measured during a Phase 1b study of VRG50635 in Amyotrophic Lateral Sclerosis (ALS). Fifty-four participants with ALS were enrolled and participated in an 8-week pretreatment run-in, followed by three 8-week dosing periods and an 8-week follow-up. They completed a speech assessment every two weeks in the clinic or at home. We observed moderate to high correlations between digital measures of speech timing and articulatory motor function, and the ALS Functional Rating Scale-Revised, slow vital capacity and plasma neurofilament light chain. Furthermore, speech measures can show functional decline before the ALSFRS-R does, while also capturing differences between participants with bulbar symptoms and those without. The results support the feasibility and utility of digital speech endpoints to study disease impact in ALS clinical trials.",

author = "Michael Neumann and Hardik Kothare and Meredith Bartlett and Oliver Roesler and Christiane Suendermann-Oeft and Abhishek Hosamath and Lakshmi Arbatti and David Pautler and David Suendermann-Oeft and Diego Cadavid and Scannevin, \{Robert H.\} and Ines Hoffmann and Anil Tarachandani and Tara Haley and Shane Raines and Damme, \{Philip Van\} and Pentti Tienari and Eino Solje and Manu Jokela and Angela Genge and Colleen O{\textquoteright}Connell and Eijk, \{Ruben P.A.van\} and Berg, \{Leonard H.van den\} and Vikram Ramanarayanan",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

doi = "10.1038/s41598-026-48100-6",

language = "English",

volume = "16",

journal = "Scientific Reports",

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Neumann, M, Kothare, H, Bartlett, M, Roesler, O, Suendermann-Oeft, C, Hosamath, A, Arbatti, L, Pautler, D, Suendermann-Oeft, D, Cadavid, D, Scannevin, RH, Hoffmann, I, Tarachandani, A, Haley, T, Raines, S, Damme, PV, Tienari, P, Solje, E, Jokela, M, Genge, A, O’Connell, C, Eijk, RPAV, Berg, LHVD & Ramanarayanan, V 2026, 'Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial', Scientific Reports, vol. 16, no. 1, 20088. https://doi.org/10.1038/s41598-026-48100-6

TY - JOUR

T1 - Speech-based digital endpoints track ALS progression and align with standard clinical outcomes

T2 - evidence from the VRG50635 trial

AU - Neumann, Michael

AU - Kothare, Hardik

AU - Bartlett, Meredith

AU - Roesler, Oliver

AU - Suendermann-Oeft, Christiane

AU - Hosamath, Abhishek

AU - Arbatti, Lakshmi

AU - Pautler, David

AU - Suendermann-Oeft, David

AU - Cadavid, Diego

AU - Scannevin, Robert H.

AU - Hoffmann, Ines

AU - Tarachandani, Anil

AU - Haley, Tara

AU - Raines, Shane

AU - Damme, Philip Van

AU - Tienari, Pentti

AU - Solje, Eino

AU - Jokela, Manu

AU - Genge, Angela

AU - O’Connell, Colleen

AU - Eijk, Ruben P.A.van

AU - Berg, Leonard H.van den

AU - Ramanarayanan, Vikram

PY - 2026

Y1 - 2026

N2 - We report on the utility of speech-based digital endpoints measured during a Phase 1b study of VRG50635 in Amyotrophic Lateral Sclerosis (ALS). Fifty-four participants with ALS were enrolled and participated in an 8-week pretreatment run-in, followed by three 8-week dosing periods and an 8-week follow-up. They completed a speech assessment every two weeks in the clinic or at home. We observed moderate to high correlations between digital measures of speech timing and articulatory motor function, and the ALS Functional Rating Scale-Revised, slow vital capacity and plasma neurofilament light chain. Furthermore, speech measures can show functional decline before the ALSFRS-R does, while also capturing differences between participants with bulbar symptoms and those without. The results support the feasibility and utility of digital speech endpoints to study disease impact in ALS clinical trials.

AB - We report on the utility of speech-based digital endpoints measured during a Phase 1b study of VRG50635 in Amyotrophic Lateral Sclerosis (ALS). Fifty-four participants with ALS were enrolled and participated in an 8-week pretreatment run-in, followed by three 8-week dosing periods and an 8-week follow-up. They completed a speech assessment every two weeks in the clinic or at home. We observed moderate to high correlations between digital measures of speech timing and articulatory motor function, and the ALS Functional Rating Scale-Revised, slow vital capacity and plasma neurofilament light chain. Furthermore, speech measures can show functional decline before the ALSFRS-R does, while also capturing differences between participants with bulbar symptoms and those without. The results support the feasibility and utility of digital speech endpoints to study disease impact in ALS clinical trials.

UR - https://www.scopus.com/pages/publications/105043457610

U2 - 10.1038/s41598-026-48100-6

DO - 10.1038/s41598-026-48100-6

M3 - Article

AN - SCOPUS:105043457610

SN - 2045-2322

VL - 16

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 20088

ER -

Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial

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