Clinical trial: Safety, Tolerability, and Activity Study of ISIS SOD1Rx to Treat Familial Amyotrophic Lateral Sclerosis (ALS) Caused by SOD1 Gene Mutations (NCT01041222)

Eligibility criteria:
Inclusion Criteria:

          -  Clinical signs of weakness attributed to ALS.

          -  Familial ALS with a documented SOD1 gene mutation.

          -  Age 18 years or older.

          -  Capable of providing informed consent and willing to comply with trial procedures and
             time commitments.

          -  Vital capacity (VC) at least 50% predicted value for gender, height and age at
             screening and not using invasive respiratory support.

          -  If taking riluzole, patients must be on stable dosage for at least 30 days prior to
             starting the study and expect to remain at that dosage until the end of the study.

          -  Medically able to undergo temporary insertion of intrathecal catheter.

          -  Normal test results for coagulation parameters.

        Exclusion Criteria:

          -  Treatment with another investigational drug for ALS (e.g. pyrimethamine, ceftriaxone,
             lithium, tamoxifen, arimoclomol, high dose creatine, biological agent, or device
             within 1-month of Screening or 5 half-lives of study agent, whichever is longer. No
             prior treatment with siRNA, cell transplant, or gene therapy is allowed.

          -  Dosing in ISIS 333611-CS1 in a previous dose cohort within 60 days of screening.

          -  Presence of any of the following clinical conditions:

               1. Drug abuse or alcoholism within one year of the Screening visit.

               2. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic function, or
                  active infectious disease.

               3. Documented history of HIV infection.

               4. Unstable psychiatric illness defined as psychosis or untreated major depression
                  within 90 days of the Screening Visit.

          -  Any condition that may impact intrathecal infusion including:

               1. History of structural spinal disease including tumors and hyperplasia.

               2. Presence of an implanted shunt for the drainage of CSF or an implanted CNS
                  catheter.

               3. Clinically significant abnormalities in hematology or clinical chemistry
                  parameters as assessed by the Site Investigator during the Screening visit.

               4. Ongoing medical condition that according to the Site Investigator would interfere
                  with the conduct and assessments of the study. Examples are medical disability
                  (e.g., severe degenerative arthritis, compromised nutritional state, peripheral
                  neuropathy) that would interfere with the assessment of safety and efficacy of
                  study material or device performance, or would compromise the ability of the
                  patient to undergo study procedures.

               5. ALT or AST >/= 3 x ULN, unless discussed with and approved by the Medical
                  Monitor.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): 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 description (patient's own words): 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.

Does the patient match the trial criteria? Entailment