Mesenchymal Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease which affects the motor neurons of the brain and spinal cord and progresses to paralysis of all muscles (including respiratory and swallowing muscles), and a fatal outcome within a median period of 2-3 years. There is now no available treatment which can halt the progression of the disease. Stem cells treatment may provide a novel approach for neuroprotection. There are several types of stem cells sharing the common feature of self-renewal and transdifferentiation to other cell types. Adult stem cells can be isolated from different body tissues. One of the richest sources for adult stem cells is the bone marrow which contains hematopoietic stem cells (HSC) and the mesenchymal stem cells (MSC). MSCs, in addition to nourishing the HSC, have additional properties: they have a self renewal capacity and may differentiate along the mesenchymal lineage into bone, fat and cartilage cells. They may also transdifferentiate and produce in vitro, cells of the neuronal lineage. MSC may represent the most suitable stem cells type for future uses in clinical practice, since they can be obtained from every adult (including the patients themselves), cultured and expanded easily to large quantities and carry very low risk for malignant transformation. Transplantation of MSCs in animal models of Parkinson's disease, ALS and MS, were shown to induce significant recovery of the affected nerves. Specifically for ALS, transplanted NTF-MSCs into the cerebral ventricular and into the leg muscles improved the motor performance of the mice, delayed the onset of the disease and increased longevity.

The main goal of our study is to evaluate the safety and efficacy of treatment with MSCs in patients with ALS. We will use MSCs obtained from patients themselves, modified to produce growth factors (MSC-NTF) and inject them either in the affected muscles or in the cerebrospinal fluid. A total of 24 ALS patients with definite diagnosis of ALS will be included. The patients will be divided into two treatment groups:

The first group consisting of 12 patients with early ALS will receive intramuscular injections with MSC-NTF cells at multiple muscle sites. The rationale for this type of treatment in this early stage group is that there is still not significant muscle atrophy and the neurotrophic factors produced by the inoculated stem cells can act locally on the end plates and nerve terminals or be transported retrogradely by the still surviving lower motor axons to the nerve cell bodies within the anterior horns of the spinal cord, to prevent further neuronal damage.

The second group, also of 12 patients who have a more progressive disease, will receive an intrathecal injection of MSC-NTF cells in order to induce the production of neurotrophic factors in the CSF and affect the motor neurons at the levels of spinal cord or anterior roots. There is also a possibility that the cells will migrate from the CSF into spinal cord parenchyma and exert their protective effects directly on motor neuron cell bodies. We have initial data indicating stabilization of the progression of ALS, in patients treated with intrathecal injections of MSC.

The overall goal of our study is to evaluate the safety and possible efficacy of autologous MSC-NTF in ALS. Our major hypothesis is that the use of stem cells may increase the survival or induce the renewal of the affected degenerative motor neurons in ALS and therefore may slow the progression of symptoms or improve the neurological disability.