Furthermore a theoretical framework exists suggesting that cells injected directly into the subarachnoid space can be a safe approach. Current clinical trials are based on two main administration strategies: the systemic and local approaches Stem cell delivery into the spinal cord and the placement into the frontal motor cortex have been described and reported as safe methods After introducing stem cells into the subarachnoid space of the spinal cord, these cells can be transported by cerebrospinal fluid (CSF) and delivered more accurately to the injured areas than is expected by using the systemic route. Several adult stem cells are available including mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) derived from several sources, including BM, adipose tissue and umbilical cord blood.Ĭlinical studies using stem cells in humans have been described in Huntington’s disease, Parkinson’s disease, spinal cord injury, stroke, and Batten’s disease. These cells can be more easily isolated from the peripheral blood or bone marrow (BM), and they remain the main source of stem cells capable of differentiation into several types, such as osteoblasts, chondrocytes, endothelial cells, glia, neurons, and skeletal and cardiac myocytes. Adult stem cells are found within many tissues of the body. A variety of cell sources have been considered for cell therapy, adult and embryonic stem cells can differentiate into several specialized lineages. Stem cell infusion could be a potential therapeutic strategy, based not only on cell replacement but also on the modification of the extracellular motor neuronal environment, through trophic and neuroprotective effects. Stem cell therapy is considered another method for treating neurodegenerative disorders, including ALS. However, this drug only slightly delays disease progression. Riluzole is the only medication approved by the FDA. There is no effective therapy for ALS patients. According to different series, mean survival of ALS patients ranges from 15.7 months to 47 months after presentation. Motor phenotypes are highly heterogeneous and are defined by: 1) the body region of onset 2) the relative mix of UMN and LMN involvement and 3) the rate of progression. Clinical features are attributable to the superimposition of motor deficits occurring in the upper motor neuron (UMN) and lower motor neuron (LMN). Key wordsĪmyotrophic lateral sclerosis (ALS), safety, stem cells, bone marrow, hematopoietic stem cell transplantationĪbbreviations: ALS: Amyotrophic lateral sclerosis ALSFRS-r: Amyotrophic lateral sclerosis functional rating scale revised BM: Bone marrow CBC: Complete blood cell count CSF: Cerebrospinal fluid CTCAE: Common terminology criteria for adverse events FVC: Forced vital capacity IT: Intrathecal LMN: Lower motor neuron MMSE: Mini mental state examination MN: Motor neuron MNC: Mononuclear cells MRI: Magnetic resonance imaging OD: onset to diagnosis OI: Onset to inclusion UMN: Upper motor neuron IntroductionĪmyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by rapid deterioration and selective death of motor neurons (MNs) in the cerebral cortex, brain stem, and spinal cord. Further studies with a greater number of patients are necessary to define the usefulness of intrathecal stem cell therapy in ALS patients. Four patients died, mortality was associated to scores lower than 30 points at inclusion.ĭiscussion: Intrathecal stem cell injection is safe, and well tolerated in ALS patients. Mean ALSFRS-R at inclusion and six months was 33 and 32, respectively. Interval between onset and stem cell injection was 23.8 months. Results: Eight females and 7 males were included (mean 47.6 years). Then, CD34+ stem cells (150 ml) were bone marrow obtained and intrathechally injected. They received subcutaneous filgrastim (600 mg) for 3 days. ALS functional rating scale revised (ALSFRS-R) was performed. Methods: Fifteen ALS patients were enrolled. Safety and feasibility of intrathecal autologous stem cell injections in ALS patients is described. Introduction: There is no effective therapy for amyotrophic lateral sclerosis (ALS).
0 Comments
Leave a Reply. |