Richard Bedlack
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View article: Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression
Peripheral immune patterns enable robust cross-platform prediction of ALS onset and progression Open
Amyotrophic lateral sclerosis (ALS) progression rates vary dramatically between patients, yet the basis of this heterogeneity remains elusive, with no prognostic biomarkers existing to guide clinical decisions or stratify patients for ther…
View article: ALSUntangled #75: Portable neuromodulation stimulator therapy
ALSUntangled #75: Portable neuromodulation stimulator therapy Open
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 i…
View article: The gut microbiota modulates the rate of ALS progression
The gut microbiota modulates the rate of ALS progression Open
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that can progress at varying rates; however, the factors influencing progression rates in ALS patients remain unknown. In this study, we report distinct microbi…
View article: ALSUntangled #78: Zinc
ALSUntangled #78: Zinc Open
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). In this review, we assess the utilization of dietary zinc supplements for modulating ALS pathology and progression. Stud…
View article: Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis
Efficacy and Safety of Zilucoplan in Amyotrophic Lateral Sclerosis Open
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 …
View article: The Scientific and Therapeutic Rationale for Off‐Label Treatments in Amyotrophic Lateral Sclerosis
The Scientific and Therapeutic Rationale for Off‐Label Treatments in Amyotrophic Lateral Sclerosis Open
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 dysfunct…
View article: ALSUntangled #76: Wahls protocol
ALSUntangled #76: Wahls protocol Open
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 p…
View article: Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype
Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype Open
This study was registered with ClinicalTrials.gov (NCT03464903) on March 14, 2018. The first participant was enrolled on June 22, 2018.
View article: Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis
Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis Open
Introduction/Aims Expanded access (EA) is a Food and Drug Administration‐regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this rep…
View article: Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration
Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration Open
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies for ALS, particularl…
View article: Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis
Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis Open
The current pipeline is larger and more diverse than ever, with drugs targeting potential genetic and retroviral causes of ALS and drugs targeting a wide array of downstream pathways, including RNA metabolism, protein aggregation, integrat…
View article: ALSUntangled #74: Withania Somnifera (Ashwagandha)
ALSUntangled #74: Withania Somnifera (Ashwagandha) Open
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 slowi…
View article: TDP-43 pathology links innate and adaptive immunity in amyotrophic lateral sclerosis
TDP-43 pathology links innate and adaptive immunity in amyotrophic lateral sclerosis Open
Amyotrophic lateral sclerosis is the most common fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, Transactive Response DNA Binding protein (TDP-43). Despite the prevalence TDP-43 …
View article: ALSUntangled #71: Nuedexta
ALSUntangled #71: Nuedexta Open
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 …
View article: Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave
Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave Open
In patients with amyotrophic lateral sclerosis (ALS), disease symptoms and pathology typically spread in a predictable spatiotemporal pattern beginning at a focal site of onset and progressing along defined neuroanatomical tracts. Like oth…
View article: ALSUntangled #70: caffeine
ALSUntangled #70: caffeine Open
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 c…
View article: Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis
Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis Open
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 patient…
View article: Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model
Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model Open
We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor defic…
View article: ALSUntangled #68: ozone therapy
ALSUntangled #68: ozone therapy Open
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant…
View article: Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset
Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset Open
Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleo…
View article: ALSUntangled #66: antimycobacterial antibiotics.
ALSUntangled #66: antimycobacterial antibiotics. Open
Several infections have been associated with motor neuron diseases resembling ALS, including species of viruses, bacteria, and parasites. Mycobacterium avium subspecies paratuberculosis (MAP), most known for its probable etiologic associat…
View article: Study of “ALS reversals”: LifeTime environmental exposures (StARLiTE)
Study of “ALS reversals”: LifeTime environmental exposures (StARLiTE) Open
We previously reported on a series of patients diagnosed with ALS whom had an extraordinary course defined by substantial and sustained improvement in weakness and function. For this study, twenty-five of these "ALS Reversals" completed ex…
View article: Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset
Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset Open
Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleo…
View article: ALSUntangled #64: butyrates
ALSUntangled #64: butyrates Open
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review butyrate and its different chemical forms (butyrates). Butyrates have plausible mechanisms for slowing AL…
View article: Phase <scp>2B</scp> randomized controlled trial of <scp>NP001</scp> in amyotrophic lateral sclerosis: Pre‐specified and post hoc analyses
Phase <span>2B</span> randomized controlled trial of <span>NP001</span> in amyotrophic lateral sclerosis: Pre‐specified and post hoc analyses Open
Introduction/Aims ALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the pla…
View article: MN-166 (ibudilast) in Amyotrophic Lateral Sclerosis in a Phase IIb/III Study: COMBAT-ALS Study Design
MN-166 (ibudilast) in Amyotrophic Lateral Sclerosis in a Phase IIb/III Study: COMBAT-ALS Study Design Open
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective ac…