Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Brooke Krivickas¹, Erica Scirocco¹, Elisa Giacomelli¹, Saloni Sharma¹, Molly Benson¹, Mackenzie Keegan¹, Jennifer Kulesa-Kelley¹, Lori B Chibnik¹, Gabriella Casagrande¹, Lindsay Heyd¹, Marianne Chase¹, Kristin Drake¹, Silpa Mohapatra¹, Jennifer Linn Hagar¹, Meredith Gibbons Hasenoehrl¹, Derek Dagostino¹, Alexander V Sherman¹, Alex Leite¹, Hong Yu¹, Jesse Rosenthal¹, Timothy Miller², Alexandra McCaffrey¹, Kelly Gwathmey³, Eduardo Locatelli⁴, Elham Bayat⁵, Daragh Heitzman⁶, Eufrosina Young⁷, Namita A Goyal⁸, Jackie Whitesell⁹, Kevin Felice¹⁰, Hristelina Ilieva¹¹, Andrea Swenson¹², David Walk¹³, Gustavo Alameda¹⁴, Laura Foster¹⁵, Courtney E McIlduff¹⁶, Alison Walsh¹⁷, Lindsay Zilliox¹⁸, Senda Ajroud-Driss¹⁹, Cynthia Bodkin²⁰, Jonathan Katz²¹, Shafeeq Ladha²², Michael Rivner²³, Laura Rosow²⁴, Paul Twydell²⁵, Warren Wasiewski²⁶, Suma Babu¹, James D Berry¹, Sabrina Paganoni^{1

27}

Affiliations

¹ Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Washington University School of Medicine, St. Louis, Missouri, USA.
³ Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ Nova Southeastern University, Davie, Florida, USA.
⁵ George Washington University, Washington, DC, USA.
⁶ Texas Neurology, Dallas, Texas, USA.
⁷ Upstate Medical University, Syracuse, New York, USA.
⁸ University of California Irvine, Orange, California, USA.
⁹ Saint Alphonsus, Boise, Idaho, USA.
¹⁰ Hospital for Special Care, New Britain, Connecticut, USA.
¹¹ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹² University of Iowa, Iowa City, Iowa, USA.
¹³ University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ Holy Cross Hospital, Fort Lauderdale, Florida, USA.
¹⁵ University of Colorado Anschutz, Aurora, Colorado, USA.
¹⁶ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁷ Lehigh Valley Health Network, Allentown, Pennsylvania, USA.
¹⁸ University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹⁹ Northwestern University, Chicago, Illinois, USA.
²⁰ Indiana University, Indianapolis, Indiana, USA.
²¹ California Pacific Medical Center, San Francisco, California, USA.
²² Barrow Neurological Institute, Phoenix, Arizona, USA.
²³ Augusta University, Augusta, Georgia, USA.
²⁴ University of California San Francisco, San Francisco, California, USA.
²⁵ Spectrum Health, Grand Rapids, Michigan, USA.
²⁶ Seelos Therapeutics, New York, New York, USA.
²⁷ Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40857020
PMCID: PMC12428506
DOI: 10.1002/mus.70011

Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Brooke Krivickas et al. Muscle Nerve. 2025.

. 2025 Aug 26:10.1002/mus.70011.

doi: 10.1002/mus.70011. Online ahead of print.

Authors

Affiliations

¹ Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Washington University School of Medicine, St. Louis, Missouri, USA.
³ Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ Nova Southeastern University, Davie, Florida, USA.
⁵ George Washington University, Washington, DC, USA.
⁶ Texas Neurology, Dallas, Texas, USA.
⁷ Upstate Medical University, Syracuse, New York, USA.
⁸ University of California Irvine, Orange, California, USA.
⁹ Saint Alphonsus, Boise, Idaho, USA.
¹⁰ Hospital for Special Care, New Britain, Connecticut, USA.
¹¹ Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹² University of Iowa, Iowa City, Iowa, USA.
¹³ University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ Holy Cross Hospital, Fort Lauderdale, Florida, USA.
¹⁵ University of Colorado Anschutz, Aurora, Colorado, USA.
¹⁶ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁷ Lehigh Valley Health Network, Allentown, Pennsylvania, USA.
¹⁸ University of Maryland School of Medicine, Baltimore, Maryland, USA.
¹⁹ Northwestern University, Chicago, Illinois, USA.
²⁰ Indiana University, Indianapolis, Indiana, USA.
²¹ California Pacific Medical Center, San Francisco, California, USA.
²² Barrow Neurological Institute, Phoenix, Arizona, USA.
²³ Augusta University, Augusta, Georgia, USA.
²⁴ University of California San Francisco, San Francisco, California, USA.
²⁵ Spectrum Health, Grand Rapids, Michigan, USA.
²⁶ Seelos Therapeutics, New York, New York, USA.
²⁷ Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 40857020
PMCID: PMC12428506
DOI: 10.1002/mus.70011

Abstract

Introduction/aims: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

Methods: Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.

Results: Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).

Discussion: This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.

Trial registration: ClinicalTrials.gov: NCT05597436.

Keywords: amyotrophic lateral sclerosis; expanded access; investigational product; motor neuron disease; trehalose.

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Conflict of interest statement

Disclosure of Conflicts of Interest

The remaining authors declare no potential conflicts of interest.

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References

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Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

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Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

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