Clinical trial NCT02228915: Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis
Official title: Analysis of Post-Translational Modifications of a Critical Protein Implicated in Amyotrophic Lateral Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ALS
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2014-08-29
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: SALS patients SOD1 associated FALS patients Healthy control

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.

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

Eligibility criteria: Inclusion Criteria:

* SALS patients
* SOD1 associated FALS patients
* Healthy control

Exclusion Criteria: none

Primary outcomes:
measure: Post-translational modifications (PTMs) of Cu/Zn superoxide dismutase 1
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Neurology ALS clinic
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Chafic Karam, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC
name: Nikolay V Dokholyan, PhD
role: PRINCIPAL_INVESTIGATOR
References: