A Trial of Tocilizumab in ALS Subjects

Inclusion Criteria: * Participants with ALS (El Escorial criteria: possible, laboratory-supported probable, probable or definite) * Capable of providing informed consent and complying with trial procedures. * High inflammatory profile of PBMC gene expression * Upright SVC ≥40% of predicted value for gender, height and age at Screening and in the opinion of the investigator is able to comply with and complete the trial. * Women must not be able to become pregnant for the duration of the study. * Negative tuberculosis blood or skin test at Screening * Not taking riluzole, or on a stable dosage for at least 30 days prior to Screening. * Subjects medically able to undergo lumbar puncture (LP) * Subjects must agree not to take live attenuated vaccines 30 days before Screening, throughout the duration of the trial and for 60 days following the subject's last dose of study drug * Geographic accessibility to the study site Additional MRI-PET Inclusion Criteria (MGH only): * High or mixed affinity to bind TSPO protein (Ala/Ala or Ala/Thr) (see section 7.1) * Upper Motor Neuron Burden (UMNB) Scale Score ≥25 (out of 45) at the Screening Visit. * Able to safely undergo MRI-PET scans based on the opinion of the site investigator. Exclusion Criteria: * Prior use of Tocilizumab, cell-depleting therapies, alkylating agents, total lymphoid irradiation * Stem cell therapies * Dependence on mechanical ventilation as defined as being unable to lay supine without it, unable to sleep without it, or continuous daytime use * Presence of tracheostomy at Screening * Exposure to any anti-inflammatory agent currently under investigation for the treatment of patients with ALS (off label use or investigational) within 30 days prior to the Screening Visit (examples include NP001 and Lunasin). Medications that do not have an anti-inflammatory mechanism, such as mexiletine or retigabine are allowed if on stable dose for 30 days prior to Screening visit * Treatment with a prohibited medication within 30 days of the Screening Visit * Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of Screening * Presence of diaphragm pacing system at Screening. * Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation * History of or active diverticulitis, diverticulosis requiring antibiotic treatment, peptic ulcer disease, or gastrointestinal (GI) tract perforation, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations * Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections. * History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies * Presence of any of the following clinical conditions: bleeding diathesis, or any other clinical condition that would, in the opinion of the investigator, place the patient at increased risk during LP. Drug abuse or alcoholism within the past 12 months. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease, including current or prior malignancy. Rheumatic autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis. Evidence of active malignant disease, malignancies diagnosed within the previous 5 years, or breast cancer diagnosed within the previous 5 years. Human immunodeficiency virus infection or other immunodeficient state.Uncontrolled hypertension defined as systolic blood pressure \> 170 or diastolic blood pressure \> 110. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the Screening Visit * Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening * Screening alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin \> than 1.5 times the upper limit of normal (ULN), serum creatinine \> 1.6 mg/dL in female patients and \> 1.9 mg/dL in male patients (patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rate (GFR) are \>30), hemoglobin \< 85 g/L, white blood cells \< 3.0 x 109/L, absolute neutrophil count of \<2000/mm3, absolute lymphocyte count \< 0.5 x 109/L, platelet concentration of \<100,000/mm3, positive Hepatitis B surface antigen (HBsAg) * Pregnant women or women currently breastfeeding * No history of chicken pox infection or no history of varicella zoster vaccination * Any reason in the opinion of the investigator that the patient may not be able to comply with study procedures, complete the study or is unsuitable for immunosuppressive therapy. Additional MR-PET Exclusion Criteria (MGH only): * Any contraindication to undergo MRI studies such as * History of a cardiac pacemaker or pacemaker wires * Metallic particles in the body * Vascular clips in the head * Prosthetic heart valves * Claustrophobia * Radiation exposure that exceeds the site's current guidelines * Current use of tobacco products including cigarettes, e-cigarettes, cigars, snuff and chewing tobacco, or nicotine replacement products such as gum, or patch * Taking any other anti-inflammatory or immune modulating medications except for over the counter NSAIDs * Unwilling or unable to discontinue benzodiazepine usage (other than Lorazepam, Clonazepam, or Zolpidem) for one day prior to scanning