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

Study Purpose:

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.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS, Healthy Volunteer, Healthy Volunteer with a Family History of ALS

Study Type:

Observational Study

Study Category:

Diseases, Study Type, Study Status, Phase, Gender

Study Status:

Active, currently recruiting

Phase:

Not Applicable

Study Chair(s)/Principal Investigator(s):

Chafic Karam, MD University of North Carolina, Chapel Hill
Nikolay V Dokholyan, PhD University of North Carolina

Clinicaltrials.gov ID (11 digit #):

NCT02228915

Neals Affiliated?

No

Coordinating Center Contact Information

UNC Neurology ALS Clinic
Manisha Chopra / .(JavaScript must be enabled to view this email address) / 919-843-7857
.(JavaScript must be enabled to view this email address) Chapel Hill, North Carolina 27599 United States

Full Study Summary:

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 Sponsor:

University of North Carolina, Chapel Hill

Participant Duration:

Estimated Enrollment:

30

Estimated Study Start Date:

07/31/2014

Estimated Study Completion Date:

07/31/2016

Posting Last Modified Date:

11/02/2016

Date Study Added to alsconsortium.org:

08/19/2015
  • More Information
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Study Population
    SALS patients SOD1 associated FALS patients Healthy control
    Criteria

    Inclusion Criteria:
    -SALS patients
    -SOD1 associated FALS patients
    -Healthy control

    Exclusion Criteria: none

  • Site Contact Information

    UNC Neurology ALS Clinic
    Manisha Chopra / .(JavaScript must be enabled to view this email address) / 919-843-7857
    Chapel Hill, North Carolina 27599
    United States