Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder for which treatment consists mainly of palliative care. Two drugs are currently widely available in the US for treatment, Riluzole and Edaravone, which can mildly attenuate motor decline and slightly prolong survival. Stem cells are currently being explored as treatment possibilities because of their ability to differentiate to healthy motor neurons and astrocytes especially, which are thought to be a major source of the neuronal damage by engaging in a positive feedback loop of neuroinflammation. Various stem cell types are also known to secrete neurotrophic factors which can promote healthy astrocyte function and mediate axonal regeneration and repair. This leads to two broad classifications of stem cell therapies: Replacement and Nonreplacement. Replacement therapies tend to use neural stem cells to supplant the host’s diseased astrocytes and create a healthy environment. Motor replacement is less feasible due to the distance they need to grow to reach the neuromuscular junction and difficulties of integration. Non-replacement therapies tend to use bone marrow mesenchymal stromal cells and tend to focus on immunomodulation to reduce damage to the motor neurons. Results from animal trials and phase I/II clinical trials show that both types of treatment using stem cells such as neural stem cells, bone marrow mesenchymal stem cells, dental pulp, and adipose derived stem cells can reduce neuroinflammation and motor neuron degradation, attenuate motor decline, and in many cases prolong survival. Future studies should look to the application of combined replacement and non-replacement strategies using both neural stem cells and mesenchymal stem cells to achieve an even greater level of neuroprotection.

Keywords

ALS, neural stem cells, embryonic stem cells, mesenchymal stromal cells, neuroinflammation