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Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis (SOD1)

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ClinicalTrials.gov Identifier: NCT02228915
Recruitment Status : Completed
First Posted : August 29, 2014
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
The purpose of this research study is to discover and quantitate the differences in post-translational modifications found in the Cu, Zn superoxide dismutase (SOD1) of patients with amyotrophic lateral sclerosis (ALS) as compared to healthy individuals. SOD1 is a known genetic cause of ALS. With certain mutations, SOD1 gains a toxic function which leads to motor neuron death.

Condition or disease
ALS

Detailed Description:
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which mutations in human Cu, Zn Superoxide Dismutase (SOD1) have been identified as a cause of familial ALS (FALS) cases.1-2 It has been shown that mutant SOD1 develops a novel toxic function through experiments demonstrating that many disease mutants maintain enzymatic activity, SOD1-null mice do not exhibit ALS symptoms, and co-expressed wild type protein does not rescue the disease-state.7-11 The majority of cases, however, are not caused directly by mutations of SOD1, instead being caused by a poorly understood interplay of several genes as well as environmental factors, which is often referred to as sporadic ALS (SALS).3 It has been found that FALS and SALS share similar pathology. 4-6 The hSOD1 protein aggregates characteristic of FALS have also been found in SALS patients, furthering the evidence that hSOD1 has an important role in the etiology of ALS in sporadic ALS patients.16-19 The exact mechanism of SOD1-associated toxicity has not yet been elucidated though many disease mutants have been shown to destabilize the SOD1 dimer. In this study we aim to compare the levels of SOD1 post-tra slational modifications in ALS patients to levels in healthy donors and to determine if there are distinct patterns of protein glutathionylation or phosphorylation. Our overall goal is to elucidate a direct mechanism of toxicity in SALS as well as identify potentially critical triggers

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Study Type : Observational
Actual Enrollment : 21 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis
Actual Study Start Date : August 2014
Actual Primary Completion Date : October 14, 2018
Actual Study Completion Date : October 16, 2018





Primary Outcome Measures :
  1. Post-translational modifications (PTMs) of Cu/Zn superoxide dismutase 1 [ Time Frame: 6 months ]

Biospecimen Retention:   Samples With DNA
A portion of this sample will be stored for future use in study of ALS and how the critical protien affects the disease progression long term. This sample will be stored de-identified; therefore will not be linked to any identifying informaton about the subject. Sample will be stored at the UNC biophysics and Biochemistry lab indefinitely


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
SALS patients SOD1 associated FALS patients Healthy control
Criteria

Inclusion Criteria:

  • SALS patients
  • SOD1 associated FALS patients
  • Healthy control

Exclusion Criteria: none


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02228915


Locations
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United States, North Carolina
UNC Neurology ALS clinic
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
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Principal Investigator: Chafic Karam, MD University of North Carolina, Chapel Hill
Principal Investigator: Nikolay V Dokholyan, PhD UNC

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02228915     History of Changes
Other Study ID Numbers: 14-1780
First Posted: August 29, 2014    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases