Please select the eligibility criteria that correspond to the clinical trial below.
Title: Explorative Trial to Investigate the Safety and Clinical Effects of Autologous Mesenchymal Bone Marrow Stem Cells (MSC) Following Their Intrathecal and Intravenous Administration in Severe Cases of Multiple Sclerosis (MS)
Brief Summary: Although, effective immunotherapies for MS exist which downregulate the anti-myelin reactivity and reduce the rate of relapses of the disease, there is no effective means today to stop the progression of disability and induce remyelination. Neuronal stem cells were shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells were tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions. Adult bone marrow derived stromal cells (MSC) were shown to induce similar (to neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE). MSCs offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, MSCs carry a safer profile and are less prone to malignant transformation.

Our initial clinical experience with 10 patients with ALS and 10 with multiple sclerosis show that intravenous and intrathecal administration of MSCs is feasible and safe.

In this study we propose an explorative protocol with the injection of MSCs (both intrathecally and intravenously) in patients with MS, in an effort to prevent further neurodegeneration through neuroprotective mechanisms and induce neuroregeneration and restoration of neuronal function.

The primary endpoint will be to further evaluate the safety and feasibility of the treatment with MSC infusions, in MS patients. Additionally, the migration ability of the transplanted cells will be evaluated by tagging MSCs with the superparamagnetic iron oxide particle (Feridex) for detection by MRI. Clinically the patients will be followed by monthly evaluations of the MS functional rating scale (EDSS) scale. The MRI, will be also used to evaluate changes in the total volume of lesions in the brain and the degree of atrophy.

Significance: This project may provide information for possible therapeutic uses of this type of bone marrow adult stem cells in MS but may also serve as a pilot platform and pave the path for future applications of various types of stem cells in neurodegerative diseases, in general.


Options:
A: Inclusion Criteria:

1. El Escorial criteria for definite or probable ALS
2. Either men or non pregnant women between 20-75 years of age.
3. Patient is mentally intact and psychologically stable
4. 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
5. For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC
6. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

1. Positive test for HBV, HCV, HIV and Mycoplasma.
2. High protein in the CSF.
3. Lymphocytosis in the CSF.
4. Positive for anti-GM1 antibodies.
5. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
6. The patient is a respiratory dependent.
7. Renal failure, impaired hepatic function
8. 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
9. Active infections.
10. Participation in another clinical trial within 1 month prior to start of this study.
11. Subject unwilling or unable to comply with the requirements of the protocol.
12. Patient has not been treated previously with any cellular therapy.
B: Inclusion Criteria:

1. Consenting patients fulfilling the Poser's clinical criteria for definite MS
2. Age: 35-65, males and females
3. Duration of disease: \>5 years
4. Failure to the currently available -registered- for MS immunomodulatory treatments (ie interferons, Copaxone, immunosuppression): the lack of response to (at least two) of these treatments will be determined/defined by either an increase (deterioration) of at least one degree in the EDSS score during the last year or the appearance of at least two major relapses of MS during the same period of time (under treatment).

Exclusion criteria

1. Patients who were treated with cytotoxic medications (cyclophosphamide, Mitoxanthrobne etc) during the last 3 months prior to the inclusion
2. Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results
3. Patients with active infections
4. Patients with severe cognitive decline or inability to understand and sign the informed consent
C: Inclusion Criteria:

* Diagnose established following the World Federation of Neurology criteria
* More than 6 and less than 36 months of evolution of the disease
* Medullar onset of the disease
* More than 20 and less than 65 years old
* Forced Vital Capacity equal or superior to 50%
* Total time of oxygen saturation \<90% inferior to 2% of the sleeping time
* Signed informed consent

Exclusion Criteria:

* Neurological or psychiatric concomitant disease
* Need of parenteral or enteral nutrition through percutaneous endoscopic gastrostomy or nasogastric tube
* Concomitant systemic disease
* Treatment with corticosteroids, immunoglobulins or immunosuppressors during the last 12 months
* Inclusion in other clinical trials
* Unability to understand the informed consent
D: Inclusion Criteria:

1. Patient must fulfill El Escorial criteria (APPENDIX 2) for definite or probable ALS (sporadic and not familial)
2. Participants, either men or non pregnant women are between 20 and 75 years of age.
3. The patient is mentally intact and psychologically stable
4. Patients will be with an ALS-FRS-R scale (APPENDIX 3) of at least 30 and disease duration of less than 2 years.
5. Patient has sufficiently bulky muscles.
6. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

1. Patient has a positive test for HBV, HCV or HIV.
2. Patient has high protein in the CSF (Protein \> 70 mg/ml).
3. Patient has lymphocytosis in the CSF (lymphocytes \> 5/ml).
4. Patient is positive for anti-GM1 antibodies.
5. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
6. The patient is a respiratory dependent patient.
7. Patients with renal failure (Cr \> 2 mg/dl).
8. Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit).
9. Patients suffering from significant cardiac disease, malignant disease or any other disease that may risk the patient or interfere with the ability to interpret the results
10. Patient with active infections.
11. Participation in another clinical trial within 1 month prior to start of this study.
12. Patient has not been treated previously with any cellular therapy.
13. Subject unwilling or unable to comply with the requirements of the protocol.

Answer: B