Clinical trial: Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis (NCT01730716)

Eligibility criteria:
Inclusion Criteria:

          1. Have the ability to understand the requirements of the study, provide written informed
             consent, understand and provide written authorization for the use and disclosure of
             Protected Health Information (PHI) [per Health Insurance Portability and
             Accountability Act (HIPAA) Privacy Ruling] and comply with the study procedures.

          2. Subjects with sporadic or familial ALS, meeting the definition of laboratory-supported
             probable, probable or definite ALS according to the World Federation of Neurology El
             Escorial Criteria (Appendix A). At the time of enrollment subjects should be within 24
             months of symptom onset.

          3. Age 18 years or older.

          4. Females must have a negative serum pregnancy test and practice an acceptable method of
             contraception or be of non-childbearing potential (post-menopausal for at least 2
             years or surgically sterile [hysterectomy, oophorectomy or surgical sterilization]).

          5. Geographic accessibility to the study center and the ability to travel to the clinic
             for study visits.

          6. Presence of a willing and able caregiver.

          7. Medically able to undergo lumbar and/or cervical laminectomy or laminoplasty as
             determined by the site Principal Investigator and neurosurgeon.

          8. Medically able to tolerate the immunosuppression regimen consisting of basiliximab,
             tacrolimus, mycophenolate mofetil, prednisone and methylprednisolone as determined by
             the site PI.

          9. Agrees to the visit schedule as outlined in the informed consent.

         10. Not taking riluzole (Rilutek®) or on a stable dose for ≥ 30 days.

         11. Vital capacity ≥ 60% of predicted normal for age, height and gender measured in the
             seated position and ≥50% in supine position during the 7 days prior to surgery.

         12. Ambulatory subjects with extremity weakness and/or spasticity due to ALS. Patients
             undergoing lumbar surgery must have demonstrable weakness or spasticity in one or both
             lower extremities. Patients undergoing cervical surgery must have demonstrable
             weakness or spasticity in one or both upper extremities, with at least antigravity
             strength. Subjects must have normal neck extensor and flexor strength.

        Exclusion Criteria:

          1. Etiology of paraplegia or weakness is due to causes other than ALS.

          2. A positive result on the Panel Reactive Antibody (PRA) test, with the presence of
             specific HLA antibodies matching the HLA DNA profile of the donor cells.

          3. Any known immunodeficiency syndrome.

          4. Receipt of any investigational drug, device or biologic within 30 days of surgery.

          5. Any concomitant medical disease or condition limiting the safety to participate:

               1. Coagulopathy

               2. Active uncontrolled infection

               3. Hypotension requiring vasopressor therapy

               4. Previous spinal surgery that the neurosurgeon deems to be an obstacle to the
                  planned transplantation

               5. Skin breakdown over the site of surgery

               6. Malignancy (except for non-melanoma skin cancer)

               7. Spinal stenosis severe enough to preclude surgery (as determined by the
                  neurosurgeon)

               8. Pre-existing kyphosis by preoperative MRI or X-ray

               9. Less than 5/5 grade in neck extension and strength test at the time of surgery.

          6. Creatinine >1.5, liver function tests (SGOT/SGPT, Bilirubin, Alk Phos) > 2x upper
             limit of normal, hematocrit/hemoglobin < 30/10, total WBC < 4000, uncontrolled
             hypertension (systolic > 180 or diastolic > 100) or uncontrolled diabetes (defined as
             hemoglobin A1C >8), evidence of GI bleeding by hemoccult test, tuberculosis (TB test:
             PPD), serologic evidence of current infection with a hepatitis virus or human
             immunodeficiency virus (HIV).

          7. Presence of any of the following conditions:

               1. Current drug abuse or alcoholism

               2. Unstable medical conditions

               3. Unstable psychiatric illness including psychosis and untreated major depression
                  within 90 days of screening

          8. Any condition or ALS disease phenotype that the site PI feels may interfere with
             participation in the study or in the interpretation of study endpoints.

          9. Any condition that the neurosurgeon feels may pose complications for the surgery.

         10. Known hypersensitivity to basiliximab, tacrolimus, mycophenolate mofetil, prednisone
             or methylprednisolone.

         11. Inability to provide informed consent as determined by the site PI.

         12. Inadequate family or caregiver support as determined by the site PI.
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