Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis (SOD1)
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| ClinicalTrials.gov Identifier: NCT02228915 |
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Recruitment Status :
Completed
First Posted : August 29, 2014
Last Update Posted : October 17, 2018
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Sponsor:
University of North Carolina, Chapel Hill
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
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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 |
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| ALS |
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
| 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 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Amyotrophic lateral sclerosis
Juvenile primary lateral sclerosis
MedlinePlus related topics:
Amyotrophic Lateral Sclerosis
Primary Outcome Measures :
- 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
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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
| 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
| Principal Investigator: | Chafic Karam, MD | University of North Carolina, Chapel Hill | |
| Principal Investigator: | Nikolay V Dokholyan, PhD | UNC |
| Responsible Party: | University of North Carolina, Chapel Hill |
| ClinicalTrials.gov Identifier: | NCT02228915 |
| 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 |