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:

* - Age:18-65
* both gender
* duration of disease\<2 years
* FVC\>40% ALS-FRS\>26

Exclusion Criteria:

* - neurological and psychiatric concomitant disease
* concomitant systemic disease
* treatment with corticosteroid,Ig,immunosuppressive during 12 months.
B: Inclusion Criteria:

* Age:18-65
* both gender
* duration of disease\<2 years
* FVC\>40% ALS-FRS\>26

Exclusion Criteria:

* neurological and psychiatric concomitant disease
* concomitant systemic disease
* treatment with corticosteroid,Ig,immunosuppressive during 12 months.
C: Inclusion Criteria:

* Patients whose conditions are defined as "definite ALS"or "probable ALS"diagnostic criteria El Escorial and revised Airlie House.
* Patients who can eat a meal, excrete, or move with oneself alone, and do not need assistance in everyday life.
* Patients of less than 2 years after the onset of ALS.
* Patients whose progress of the condition during 12 weeks before administration meet other requirements.

Exclusion Criteria:

* Patients with such complications as Parkinson's disease, schizophrenia, dementia, renal failure, or other severe complication, and patients who have the anamnesis of hypersensitivity to edaravone.
* Pregnant, lactating, and probably pregnant patients, and patients who want to become pregnant, and patients who can not agree to contraception.
* Patients who have participated in other trials within 12 weeks before consent, or who are participating in other clinical trials at present.
* In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.
D: 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

Answer: D