Please select the outcome measures 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: Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) (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) (6 months)
B: Safety of one or multiple intrathecaland intravenous injections of autologous MSC in Multiple sclerosis (One year for the first phase; 4 years for the extension phase)
C: Forced vital capacity (Every 3 months)
D: Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) (At baseline and up to 6 month following treatment administration)

Answer: B