SOD1 Kinetics Measurements in ALS Patients

Study Purpose:

Washington University in St. Louis is seeking participants with ALS for a study to determine the half-life of the protein SOD1 in the cerebral spinal fluid. Mutations in the SOD1 gene are known to cause some forms of familial ALS. Researchers are developing a treatment to reduce the level of SOD1 in familial ALS, but need to know more about how long SOD1 stays in the body ("half-life") to help determine if the new treatment is effective.


Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS, Healthy Volunteer

Study Type:

Observational Study

Study Category:


Study Status:



Not Applicable

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

Timothy Miller, MD, PhD, Washington University (St. Louis) ID (11 digit #):


Neals Affiliated?


Coordinating Center Contact Information

Washington University in St. Louis
Neuromuscular Clinical Studies Line / .(JavaScript must be enabled to view this email address) / 314-362-6159
.(JavaScript must be enabled to view this email address) 660 S Euclid Ave.
St. Louis , Missouri 63110 United States

Full Study Summary:

Background: Novel targeted therapeutic strategies are being developed for genetic subsets of ALS, such as those caused by dominantly inherited mutations in the superoxide dismutase 1 gene (SOD1). Investigators have developed an antisense oligonucleotide (ASO) inhibitor of SOD1 biosynthesis for ALS patients who carry mutations in SOD1. This ASO is now ready for clinical trial ( #NCT02623699). The initial success of the ASO will depend on showing a pharmacodynamics result on SOD1 in participants, and thus a key challenge in applying this targeted therapy involves rigorous examination of pharmacodynamics markers.

The Investigator's previous data suggest that SOD1 in the cerebral spinal fluid (CSF) will be an excellent pharmacodynamics marker for an SOD1-focused therapeutic approach. However, one of the central missing components in understanding SOD1 as a marker is SOD1 CSF half-life data. The half-life of this protein will aid in clinical trial planning since half-life influences the amount of SOD1 protein reduction by ASO and thus dictates the optimal timing of drug administration and CSF collection for pharmacodynamics measures.


  • Enroll a total of 86 ALS participants
  • Determine the kinetics for total SOD1 protein, as well as the wild type and mutant protein separately
  • Determine this in patients with known SOD1 mutation as well as sporadic ALS patients Eligibility
  • Adults over age 18
  • fALS with confirmed genetic testing showing a mutation in the SOD1 gene; asymptomatic SOD1 gene carriers and sporadic ALS patients.

Measures: The key outcome of this study is to determine the half-life of the SOD1 protein in symptomatic and asymptomatic ALS patients which will provide critical information to inform future therapeutic studies in ALS. For ALS patients, The Investigators will also perform Slow Vital Capacity testing and the ALSFRS-R at the screening visit and at each lumbar puncture visit.

Measures: Participants will have up to 7 in-person visits over 4 months. The study involves labeling or marking SOD1 with a special type of leucine. Leucine is an essential amino acid that is found in the foods we eat. This method involves an overnight stay for a 16 hour intravenous infusion of labeled leucine along with a collection blood and urine followed by 5 lumbar punctures scheduled over the period of 4 months.

At each subsequent visit, subjects will undergo a blood draw, urine collection, lumbar puncture, a questionnaire (ALS Functional Rating Scale) which measures motor function, and a breathing test to determine Slow Vital Capacity (SVC) measurements.

Analysis: In addition to determining the half-life of the SOD1 protein in ALS patients, the Investigators will also analyze the kinetics of wild type SOD1 protein separately from mutant SOD1 protein to determine differences in half life. The Investigators will also compare CSF Tau half-life between ALS patients and controls as a disease specificity control. The Investigators hope to correlate this data with clinical measures which may reveal other important hypotheses regarding SOD1 kinetic rates and disease manifestations.

Study Sponsor:

Washington University School of Medicine

Participant Duration:

1 overnight stay for leucine infusion. 4-5 lumbar punctures performed over a period of 3-4 months at Washington University. Each lumbar puncture visit takes approximately three hours.

Estimated Enrollment:


Estimated Study Start Date:


Estimated Study Completion Date:


Posting Last Modified Date:


Date Study Added to

  • Eligibility Criteria


    Female, Male

    Minimum Age:


    Maximum Age:


    Time since Symptom Onset:


    Time since Diagnosis:


    Can participants use Riluzole?


  • Site Contact Information

    Massachusetts General Hospital
    165 Cambridge Street
    Boston, Massachusetts 20114
    United States

    Washington University
    Saint Louis, Missouri 63110
    United States