Phase I clinical trial of safety of L-serine for ALS patients

  title={Phase I clinical trial of safety of L-serine for ALS patients},
  author={Todd D. Levine and Robert G. Miller and Walter G Bradley and D. Moore and David S. Saperstein and Lynne E Flynn and Jonathan S. Katz and Dallas A. Forshew and James S Metcalf and Sandra Anne Banack and Paul Alan Cox},
  journal={Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration},
  pages={107 - 111}
Abstract We performed a randomized, double-blind phase I clinical trial for six months on the effects of oral L-serine in patients with ALS. The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18–85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%. Patients were randomly assigned to four different oral twice-daily dose regimens (0.5, 2.5, 7.5, or 15 g/dose). Blood, urine and CSF samples, ALS Functional Rating… 
Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial
This trial will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS.
Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of l-Serine
Abstractβ-N-Methylamino-l-alanine (BMAA) has been linked to Guam ALS/PDC and shown to produce neurodegeneration in vitro and in vivo (Drosophila, mice, rats, primates). BMAA misincorporation into
Mechanisms of l-Serine-Mediated Neuroprotection Include Selective Activation of Lysosomal Cathepsins B and L
Activation of autophagic-lysosomal proteolysis may contribute to the neuroprotective effect of l -serine, which has been reported in cell culture and human clinical trials.
Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C
It is concluded that oral supplementation of L-serine decreases 1-deoxySL in HSAN1C without major global effects on metabolism, and L-Serine is therefore a potential treatment for HSAN 1C.
l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
ABSTRACT Background Multisite pain, including low-back and knee pain, is a major health issue that greatly decreases quality of life. Objectives This study analyzed the effects of l-serine, which
Informing Pharmacokinetic Models With Physiological Data: Oral Population Modeling of L-Serine in Humans
A key contribution is that the model was able to use human physiological data from the literature to inform the PK model and to set reasonable bounds on parameters, and to improve model conditioning.
Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults
A clinical, no-observed-adverse-effect-level (NOAEL) of phenylalanine and serine supplementation in healthy adult males was determined to be 12 g/day.
Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects
Using the allometric scaling approach, this study suggested an optimal fixed-dose regimen with five weight ranges in pediatrics for the upcoming phase 2 trial of AST-001 in healthy subjects.
Amyotrophic Lateral Sclerosis (ALS): The Application of Integrative and Functional Medical Nutrition Therapy (IFMNT)
This chapter explores the metabolic and nutritional consequences of ALS and reviews dietary and supplement approaches that might optimize ALS management or potentially support reversal through personalized nutritional assessment and the application of IFMNT.


Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial
The ALSFRSr predicts survival time in an ALS clinic population
In an ALS clinic population, the total Amyotrophic Lateral Sclerosis Functional Rating Scale–revised score at baseline is a strong predictor of death or tracheostomy independently of forced vital capacity and after adjustment for age at baseline, sex, and symptom duration.
Detection of BMAA in the human central nervous system
Use of respiratory function tests to predict survival in amyotrophic lateral sclerosis
  • F. Baumann, R. Henderson, P. Mccombe
  • Medicine
    Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
  • 2010
It is shown that measurements of FVC in the supine position are worth including in the assessment of respiratory function in ALS, and a normal supine FVC was highly predictive for two-year survival and had superior sensitivity over seated FVC.
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1.
Observations support the hypothesis that an altered substrate selectivity of the mutant SPT is key to the pathophysiology of HSAN1 and raise the prospect of l-serine supplementation as a first treatment option for this disorder.
Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s disease
Objective –  The aim of this study was to screen for and quantify the neurotoxic amino acid β‐N‐methylamino‐l‐alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer’s disease (AD),
Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases?
Methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, are described, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems.
Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain
It is found that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.
Cerebral uptake and protein incorporation of cyanobacterial toxin &bgr;-N-methylamino-L-alanine
The time-dependent association of [14C]-L-BMAA in the protein-bound fraction suggests that BMAA may be trapped in new proteins by protein synthesis-dependent processes.
The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function