Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.

Study Overview
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Brief Summary
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The study will evaluate the safety, tolerability and therapeutic effects (preliminary efficacy) of injection of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a possible treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early and progressive disease stages.

Detailed Description
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This study is a single center trial to be conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. All patients enrolled will have a documented history of ALS disease prior to study enrolment. Patients diagnosed as early stage ALS disease with duration of less than 6 months and patients diagnosed with progressive stage ALS disease with duration of 6-12 months. Overall, 24 patients will be recruited and allocated based on their ALS disease severity to 2 treatment groups: Group A - 12 patients of early ALS disease stage and Group B - 12 patients of progressive ALS disease. Eligible patients will be enrolled into the study and will be observed for every 2 weeks during a run in period of 3 months for determination of the progression rate of the disease. During the run in period after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last run in period visit, patients of both study groups will undergo the treatment and MSC-NTF will be transplanted by IM or IT injection to the early and progressive ALS patients respectively. After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months.

Official Title
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A Phase I/II, Open Label Study to Evaluate Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: MSC-NTF cells transplantation (IM)
* Biological: MSC-NTF cells transplantation (IT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: El Escorial criteria for definite or probable ALS Either men or non pregnant women between 20-75 years of age. Patient is mentally intact and psychologically stable For early stage ALS- Patients will be with ALS-FRS-R scale of at least 30 and disease duration of less than 2 years.Or, for progressive stage ALS- Patients will be with an ALS-FRS-R scale of 15-30 and disease duration of less than 2 years For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC Participant understands the nature of the procedure and provides written informed consent prior to any study procedure. Exclusion Criteria: Positive test for HBV, HCV, HIV and Mycoplasma. High protein in the CSF. Lymphocytosis in the CSF. Positive for anti-GM1 antibodies. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies. The patient is a respiratory dependent. Renal failure, impaired hepatic function Patients suffering from significant cardiac disease, malignant diseases or any other disease that may risk the patient or interfere with the ability to interpret the results Active infections. Participation in another clinical trial within 1 month prior to start of this study. Subject unwilling or unable to comply with the requirements of the protocol. Patient has not been treated previously with any cellular therapy.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC-NTF cells IM<br>Intramuscular administration in early stage patients | Biological: MSC-NTF cells transplantation (IM)<br>* In early ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia, intramuscularly into patients' clinically unaffected (or only mildly affected) upper arm biceps and triceps muscles according to a pre-designed grid. Intramuscular injections will be by a 26 gauge needle to a 1.5cm depth (ensuring that injection is into muscle and not adipose tissue). The patients will be injected at 24 sites with a total of 24 million cells<br>|
| Experimental: MSC-NTF cells IT<br>Intrathecal administration in progressive stage patients | Biological: MSC-NTF cells transplantation (IT)<br>* In progressive ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia intrathecally(via a standard lumbar puncture)with a total of 60 million cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) | Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) by multiple intramuscular injections (IM) at 24 separate sites on the biceps and triceps muscles to patients with ALS at the early disease stage | 6 months | 
| Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) | Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF),to patients with ALS at the progressive disease stage. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS) |  | 6 months | 
| Changes in muscle strength grading (MVIC) by muscle chart |  | 6 months | 
| Changes in forced vital capacity (FVC %) (In the progressive disease stage group only). |  | 6 months | 
| Changes in muscle bulk estimated by MRI of the upper and lower extremities |  | 6 months | 
| Changes in upper and lower extremities circumference (cm) |  | 6 months | 
| Changes in EMG parameters |  | 6 months | 
| Need and time to tracheotomy or permanent assisted ventilation |  | 6 months | 
| Overall survival, calculating time to death |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Mesenchymal Stromal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells