Patient case (clinical description): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient's own account: I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Clinical trial: iPSC-based Drug Repurposing for ALS Medicine (iDReAM) Study

Eligibility criteria:
Inclusion criteria:

          1. Evidence of a personally signed and dated informed consent document indicating that
             the patient has been informed of all pertinent aspects of the study. To be additionaly
             signed by a delegate signer if the subject is unable to handwrite.

          2. Patients aged ≥20 years and <80 years at the time of informed consent

          3. Patients with positive already-reported SOD1 gene mutation and progressive muscle
             weakness; sporadic ALS patients who are categorized as either "Definite ALS" or
             "Probable ALS" or "Probable-laboratory supported ALS" in the Updated Awaji Criteria
             for the diagnosis of ALS

          4. Patients at Grade 1 or 2 in the Japan ALS Severity Scale of the grant-in-aid program
             for chronic diseases from the Japanese Ministry of Health, Labour and Welfare;
             patients with positive SOD1 mutation of Grade 1, 2 or 3

          5. Patients with ALS that occurred within 2 years at the time of the first registration;
             patients with positive SOD1 mutation within 5 years after disease onset

          6. Patients who can visit hospital regularly as outpatients

          7. Patients with change in total ALSFRS-R score during the observation period are -1 to
             -3 points

          8. Urine pregnancy test (for females of childbearing potential) negative at screening

             Female patients of nonchildbearing potential must meet at least 1 of the following
             criteria:

               1. Achieved postmenopausal status, defined as follows: cessation of regular menses
                  for at least 12 consecutive months with no alternative pathological or
                  physiological cause; status may be confirmed with a serum follicle stimulating
                  hormone (FSH) level confirming the postmenopausal state;

               2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

               3. Have medically confirmed ovarian failure. All other female patients (including
                  female patients with tubal ligations) are considered to be of childbearing
                  potential.

             Male and female patients of childbearing potential must agree to use one highly
             effective method of contraception as outlined in this protocol, throughout the study
             and for at least 28 days after the last dose of investigational product.

          9. Patients with appropriate renal function as defined as follows at the time of the
             first and second registrations

             a. Serum creatinine ≤1.5 × upper limit of normal (ULN) or estimated creatinine
             clearance ≥60 mL/min as calculated using the method standard for the institution.

         10. Patients with appropriate hepatic function as defined as follows at the time of the
             first and second registrations b. Total serum bilirubin ≤1.5 × ULN unless the patient
             has documented Gilbert syndrome; c. AST and ALT ≤2.5 × ULN

         11. Able to take oral tablets

         12. Patients whose acute effect of previous treatment has recovered to the baseline or
             CTCAE v.4.03 ≤ Grade 1 at the time of the first and second registrations

         13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
             and other study procedures

        Exclusion criteria:

          1. Patients with tracheostomy

          2. Patients who have used non-invasive ventilation due to ALS symptoms

          3. Patients whose %FVCs are less than 70% at the time of first and second registrations

          4. Patients who have nerve conduction study findings of demyelination such as conduction
             block

          5. Patients who are taking edaravone; patients who started riluzole or edaravone after
             start of the observation period; patients who changed the dosage of riluzole after
             start of the observation period

          6. Patients with bulbar type ALS with dysphagia and dysarthria

          7. Patients with cognitive impairment

          8. Pregnant female patients; breastfeeding female patients; fertile male and female
             patients of childbearing potential who are unwilling or unable to use 1 highly
             effective methods of contraception as outlined in this protocol for the duration of
             the study and for at least 28 days after the last dose of investigational product

          9. History of clinically significant or uncontrolled cardiac disease including:

               -  History of, or active, congestive heart failure;

               -  Uncontrolled angina or hypertension within 3 months prior to registration;

               -  Myocardial infarction within 12 months prior to registration;

               -  Clinically significant ventricular arrhythmia (such as ventricular tachycardia,
                  ventricular fibrillation, or Torsades de pointes);

               -  Diagnosed or suspected congenital or acquired prolonged QT interval history or
                  prolonged QTc (QTcF should not exceed 500 msec);

               -  Unexplained syncope

         10. Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the
             QT interval

         11. Patient who is taking the following medicines during study drugs administration.

             a Combination of warfarin or other anticoagulation. Combination of therapeutic
             anticoagulant therapy with low molecular weight heparin is acceptable b Src or c-Abl
             inhibitors c Other treatments for cancer d Drugs known to prolong the QT interval or
             predispose to Torsades de Pointe e Current or anticipated use of a strong or moderate
             CYP3A inhibitor and inducer f Drugs affecting gastric pH such as Proton pump
             inhibitors (e.g., lansoprazole)

         12. History of malignancy within 5 years prior to registration with the exception of basal
             cell carcinoma or cervical carcinoma in situ or Stage 1 or 2 cancer that is considered
             adequately treated and currently in complete remission for at least 12 months

         13. Patients who were enrolled in other clinical study within 12 weeks before the first
             registration, or are expected to be enrolled in other clinical study using a study
             drug during this study

         14. Known prior or suspected severe hypersensitivity to study drugs or any component in
             their formulations

         15. Patients with active, uncontrolled bacterial, fungal, or viral infection, including
             hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus
             (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

         16. Recent or ongoing clinically significant GI disorder (eg, Crohn's disease, ulcerative
             colitis, or prior total or partial gastrectomy).

         17. Patients with chronic obstructive pulmonary disease

         18. Major surgery or radiotherapy within 14 days prior to registration at the time of the
             first registration

         19. Patient who fulfills the conditions:

               1. Neutrophil count (ANC) <1,500/mm3 or white blood cell <3,000/mm3 at the time of
                  the first and second registration

               2. Hemoglobin <9.0 g/dL at the time of the first and second registrations

               3. Platelet count <100,000/L at the time of the first and second registrations

         20. Other acute or chronic medical or psychiatric condition including recent (within the
             past year) or active suicidal ideation or behavior or laboratory abnormality that may
             increase the risk associated with study participation or investigational product
             administration or may interfere with the interpretation of study results and, in the
             judgment of the investigator, would make the participant inappropriate for entry into
             this study

         21. Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, or
             Pfizer employees, including their family members, directly involved in the conduct of
             the study
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 20 Years old.
Subject must be at most 79 Years

Eligibility (NLI label): Entailment