Repeated Mesenchymal Stem Cell Injections in ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated
      intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS
      patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and
      ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment
      protocol includes four intrathecal injections of MSC, at intervals of 3 months between the
      injections.

      The primary endpoints are safety and tolerability. Several efficacy measures are assessed as
      secondary endpoints.
    

Detailed description: 
      An open-label, single-center clinical trial to evaluate the safety and efficacy of repeated
      intrathecal administrations of autologous bone marrow derived mesenchyme stem cells in ALS
      patients. The study includes 20 subjects (age: 20-70) with definite diagnosis of ALS and
      ALS-FRS-R score of at least 20 and disease-duration of less than 3 years. The treatment
      protocol includes four intrathecal injections of MSC, at intervals of 3 months between the
      injections. The primary endpoints are safety and tolerability. Several efficacy measures are
      assessed as secondary endpoints.

      Applications from patients are received in our centre. An independent selective committee set
      by hospital's administration examines anonymously, according to the predefined inclusion and
      exclusion criteria. After inclusion and screening visit, patients are followed up for a
      "run-in" period of 6 months before the first visit (visit 1), to evaluate the progression
      rate of their disease. and for six months following the last transplantation.

      One month after inclusion, patients undergo bone Marrow Aspiration (BMA) procedure and MSC
      cells are produced from the bone marrow aspirate. On the treatment visit, the patients are
      transplanted with an intrathecal (IT) injection of MSC (1 million cells per kg of body
      weight) and thereafter with additional injections every 3-6 months. After the MSC
      transplantation patients are examined on a bimonthly basis and evaluated for ALSFRSr scoring
      and forced vital capacity of the lungs (FVC) for a total follow up period of 3 months post
      last MSC-injection.

      To establish the progression rate of the disease the monthly changes in the functional ALS
      score: ALSFRSr will be calculated during the 6 months-"run in period" and for the whole
      duration of the study, ending at 3 months following the last injection of MSC stem cells. The
      progression rate (as evidenced by the monthly changes in ALSFRSr and FVC) during the study
      (calculated at last visit time point, 3 months after the last MSC-injection) will be compared
      to the progression rate during the "run-in" period.

      The follow up visits include observation for side effects, full neurological evaluation and
      muscle chart, ALS score and forced vital capacity (FVC) test. The safety is assessed
      following treatment with MSC, using measurements of the following variables: physical
      examination, vital signs (HR, BP, RR, body temperature), and clinical laboratory parameters:
      WBC with differential and platelet count, hemoglobin (Hb), hematocrit (Ht), blood chemistry
      for electrolytes, creatinine and liver enzymes.

      All selected patients undergo bone marrow aspiration under light general anaesthesia and an
      inoculum of crude bone marrow cells (150 ml) is obtained and two thirds of it kept frozen.
      One third is cultured under GCP conditions at the human cell cultures clean room facility of
      Hadassah HMO. The MSCs are obtained from the bone marrow of each patient and prepared using
      our previously described protocol with slight modification.

      One month later the patient is hospitalized and a lumbar puncture performed under standard
      conditions and local anaesthesia at the L4-5 lumbar level and 3 ml of CSF are removed and the
      cultured purified MSCs (1x106/kg of body weight) resuspended in 3 ml of normal saline are
      injected in the CSF, using a 20-gauge needle and 3-way cannula.
    

Intervention name(s): Mesenchymal stem cells (MSC)
Intervention type(s): Biological
Intervention description(s): Intrathecal injections of autologous bone marrow derived mesenchymal stem cells
Other intervention name(s): stem cells; Stromal cells
Intervention model: Single Group Assignment
Intervention model description: Single center open label study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ALS; Mesenchymal stem cells; ALSFRSr