Scholars@Duke
Xiaoyan Li

Xiaoyan Li

Assistant Professor of Neurology
Neurology, Neuromuscular Disease

Selected Publications

ALSUntangled #81: Pyridostigmine (mestinon®).

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · November 6, 2025 Pyridostigmine (Mestinon®, Bausch Health, Canada Inc.) increases acetylcholine availability at the neuromuscular junction, enhancing transmission. Preclinical studies suggest that neuromuscular junction dysfunction develops early in ALS, and pyridostigmine ... Full text Link to item Cite

Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the HEALEY ALS Platform Trial.

Journal Article Muscle Nerve · August 2025 INTRODUCTION/AIMS: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. METHODS: Platform-level procedures for reg ... Full text Link to item Cite

Safety and efficacy of trehalose in amyotrophic lateral sclerosis (HEALEY ALS Platform Trial): an adaptive, phase 2/3, double-blind, randomised, placebo-controlled trial.

Journal Article Lancet Neurol · June 2025 BACKGROUND: Trehalose is a disaccharide that activates autophagy pathways in animal models of neurodegenerative diseases, with the potential to catalyse clearance of toxic, misfolded proteins in motor neurons and slow disease progression in amyotrophic lat ... Full text Link to item Cite

ALSUntangled #79: alpha-lipoic acid.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · May 24, 2025 Alpha-lipoic acid (ALA) is a naturally occurring fatty acid. It serves as an essential cofactor for enzymatic reactions in mitochondrial energy production, is a potent antioxidant and has anti-inflammatory effects, which are plausible mechanisms in slowing ... Full text Link to item Cite

CNM-Au8 in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.

Journal Article JAMA · February 17, 2025 IMPORTANCE: Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD+, resulting in an increa ... Full text Link to item Cite

Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial.

Journal Article JAMA · February 17, 2025 IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention. OBJECTIVE: To determine the effects of pridopidine, a σ1-receptor agonist, in ALS. DESIGN, SETTINGS, AND PARTICIPANTS: Prido ... Full text Link to item Cite

Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Journal Article JAMA Netw Open · February 3, 2025 IMPORTANCE: The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. OBJECTIVE: To determine the effects of zilucoplan, ... Full text Link to item Cite

ALSUntangled #76: Wahls protocol.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · February 2025 The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods co ... Full text Link to item Cite

Access for ALL in ALS: A large‐scale, inclusive, collaborative consortium to unlock the molecular and genetic mechanisms of amyotrophic lateral sclerosis

Journal Article Muscle & Nerve · December 2024 AbstractRecent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persis ... Full text Cite

The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis.

Journal Article Ann Neurol · November 6, 2024 There are no dramatically effective pharmacological treatments for most patients with amyotrophic lateral sclerosis, a complex disease with multiple underlying mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, microbiome a ... Full text Link to item Cite

ALSUntangled #74: Withania Somnifera (Ashwagandha).

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · November 2024 ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progressio ... Full text Link to item Cite

ALSUntangled #75: Portable neuromodulation stimulator therapy.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · August 2024 Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients ... Full text Link to item Cite

Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis.

Journal Article Expert Opin Emerg Drugs · June 2024 INTRODUCTION: Amyotrophic Lateral Sclerosis is a rapidly progressive motor neuron disorder causing severe disability and premature death. Owing to the advances in uncovering ALS pathophysiology, efficient clinical trial design and research advocacy program ... Full text Link to item Cite

ALSUntangled #72: Insulin.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · May 2024 ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited ... Full text Link to item Cite

ALSUntangled #73: Lion's Mane.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · May 2024 Lion's Mane (Hericium erinaceus) has historically been used as traditional medicine in Asia and Europe for its potential benefits in fighting infection and cancer. It has gained interest in the neurodegenerative disease field because of its mechanisms of a ... Full text Link to item Cite

ALSUntangled #71: Nuedexta.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · February 2024 Nuedexta is a combination of dextromethorphan hydrobromide and quinidine sulfate and was approved by the Food and Drug Administration (FDA) in 2010 to treat pseudobulbar affect (PBA). There have since been anecdotal case reports of bulbar function improvem ... Full text Link to item Cite

Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis.

Journal Article Ann Neurol · September 2023 Platform trials allow efficient evaluation of multiple interventions for a specific disease. The HEALEY ALS Platform Trial is testing multiple investigational products in parallel and sequentially in persons with amyotrophic lateral sclerosis (ALS) with th ... Full text Link to item Cite

ALSUntangled #67: rituximab.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · August 2023 ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progr ... Full text Link to item Cite

ALSUntangled #70: caffeine.

Journal Article Amyotroph Lateral Scler Frontotemporal Degener · June 8, 2023 ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here, we review caffeine which has plausible mechanisms for slowing ALS progression. However, pre-clinical studies are contradictory, and ... Full text Link to item Cite

Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis.

Journal Article J Clin Neuromuscul Dis · June 1, 2023 OBJECTIVE: Clenbuterol, a beta-agonist, has plausible mechanisms for treating amyotrophic lateral sclerosis (ALS). In this highly inclusive open-label trial (NCT04245709), we aimed to study the safety and efficacy of clenbuterol in patients with ALS. METHO ... Full text Link to item Cite

An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis.

Journal Article Expert Rev Neurother · January 2023 INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative motor neuron disease. Despite the overwhelming need for effective therapeutics for ALS, riluzole and edaravone were the only two FDA-approved disease-modify ... Full text Link to item Cite

Results from a Widely-Inclusive, Historically-Controlled, Virtual Pilot Trial of Theracurmin

Conference Proceedings of the 21st Annual Meeting of the NortheastALS Consortium · November 1, 2022 Background: Curcumin is a polyphenol naturally found in turmericand curry powder. It could theoretically slow ALS progression viaeffects on neuroinflammation, oxidative stress, protein aggregationand the gut microbiome. In a cell model of ALS, curcumin tre ... Full text Cite

Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development.

Journal Article Ann Neurol · February 2022 Current therapeutic development in amyotrophic lateral sclerosis (ALS) relies on individual randomized clinical trials to test a specific investigational product in a single patient population. This approach has intrinsic limitations, including cost, time, ... Full text Link to item Cite

Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex.

Journal Article Elife · February 5, 2016 Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in deve ... Full text Link to item Cite

MEK Is a Key Regulator of Gliogenesis in the Developing Brain.

Journal Article Neuron · September 20, 2012 We have defined functions of MEK in regulating gliogenesis in developing cerebral cortex using loss- and gain-of-function mouse genetics. Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and ... Full text Link to item Cite

Specific functions for ERK/MAPK signaling during PNS development.

Journal Article Neuron · January 13, 2011 We have established functions of the stimulus-dependent MAPKs, ERK1/2 and ERK5, in DRG, motor neuron, and Schwann cell development. Surprisingly, many aspects of early DRG and motor neuron development were found to be ERK1/2 independent, and Erk5 deletion ... Full text Link to item Cite

Signaling Endosomes Trigger Synapse Assembly

Journal Article Neuron · August 1, 2010 In this issue of Neuron, Sharma et al. report that target-derived NGF exerts long-distance control of postsynaptic assembly. A major advance is the discovery that TrkA signaling endosomes are retrogradely transported to neuronal dendrites and directly trig ... Full text Cite

Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector.

Journal Article PLoS One · 2009 BACKGROUND: Regulator of G-protein signaling (RGS) proteins have been well-described as accelerators of Galpha-mediated GTP hydrolysis ("GTPase-accelerating proteins" or GAPs). However, RGS proteins with complex domain architectures are now known to regula ... Full text Link to item Cite

Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development.

Journal Article Proc Natl Acad Sci U S A · November 4, 2008 Disrupted ERK1/2 (MAPK3/MAPK1) MAPK signaling has been associated with several developmental syndromes in humans; however, mutations in ERK1 or ERK2 have not been described. We demonstrate haplo-insufficient ERK2 expression in patients with a novel approxi ... Full text Link to item Cite

Diverse effects of Stat1 on the regulation of hsp90α gene under heat shock

Journal Article Journal of Cellular Biochemistry · November 2007 AbstractStat1 has been known as a regulator of gene expression and a mediator of IFNγ signaling in mammalian cells, while its effect in a heat shock response remains unclear. We used RNAi knockdown, point mutations, ChIP an ... Full text Cite

Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo.

Journal Article Nat Neurosci · May 2007 To define the role of the Raf serine/threonine kinases in nervous system development, we conditionally targeted B-Raf and C-Raf, two of the three known mammalian Raf homologs, using a mouse line expressing Cre recombinase driven by a nestin promoter. Targe ... Full text Link to item Cite

Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation.

Journal Article EMBO J · April 18, 2007 Regulator of G-protein signaling (RGS) proteins accelerate GTP hydrolysis by heterotrimeric G-protein alpha subunits and thus inhibit signaling by many G protein-coupled receptors. Several RGS proteins have a multidomain architecture that adds further comp ... Full text Link to item Cite

Use high-dimensional immune profiling to study peripheral immune system and ALS progression

Conference Proceedings of the 22nd Annual Meeting of the Northeast ALS Consortium Full text Cite

A Retrospective Analysis of ALS Clusters Near Algae Blooms in North Carolina

Conference Objective To examine clinical differences between individuals with amyotrophic lateral sclerosis (ALS) who live near and far from harmful algal blooms (HABs) in North Carolina. Background While 10% of ALS cases are associated with genetic mutations, the r ... Cite

Use high-dimensional immune profiling to study peripheral immune system and ALS progression

Conference Neurology Title Use High-dimensional Immune Profiling to Study Peripheral Immune System and ALS Progression Topic Neuromuscular and Clinical Neurophysiology (EMG) Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM) Poster/Presentation Number 11-006 Objective ... Cite

Vanishing “Trident Sign” in Recurrent Sarcoid Myelitis Treated with Rituximab

Conference Title Vanishing “Trident Sign” in Recurrent Sarcoid Myelitis Treated with Rituximab Topic Multiple Sclerosis Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM) Poster/Presentation Number 15-064 Objective To highlight the diagnostic significance of ... Cite