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| Name | Class |
|---|---|
| Hadassah Medical Organization | OTHER |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MSC-NTF cells IM | Experimental | Intramuscular administration in early stage patients |
|
| MSC-NTF cells IT | Experimental | Intrathecal administration in progressive stage patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MSC-NTF cells transplantation (IM) | Biological | 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dimitrios Karussis, MD, PhD | Hadassah Medical Organization | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hadassah Medical Organization | Jerusalem | 91120 | Israel |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26751635 | Derived | Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321. |
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| MSC-NTF cells transplantation (IT) | Biological | 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. |
|
| 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 |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D009410 | Nerve Degeneration |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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