Stem Cell Therapy for Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease of cortical, brainstem and spinal motor neurons that leads to skeletal muscle weakness and atrophy, with death typically resulting from respiratory failure 2 to 4 years after disease diagnosis. Changes in executive function are common and occur in up to 50% of individuals and up to 15% of persons with ALS manifest frontotemporal dementia due to neuronal dysfunction in the prefrontal and temporal cortex. The incidence of ALS ranges from 1 to 4 cases per 100,000 although some subpopulations exhibit above average incidence. The disease exhibits clinical and pathophysiologic heterogeneity; both familial and sporadic cases occur. The development of targeted therapies for ALS, however, has been hindered by the fact that the mechanisms responsible for disease onset and progression largely remain unknown.

A curative treatment for ALS, able to block disease progression, has not been developed yet. Nowadays, only 2 drugs are approved by the FDA for ALS treatment: riluzole and edaravone. Riluzole is a glutamate antagonist whose mechanism of action is not fully clear, but interfere with intracellular event after the activation of excitatory amino acid receptors. Interestingly, it is able to extend the survival of ALS patients. Edaravone was recently approved by FDA and acts as an antioxidant. It is thought to be a free radical scavenger and may exert its action reducing oxidative stress in motor neurons and glial cells.

The initial symptoms of ALS can be quite varied in different people. One person may have trouble grasping a pen or lifting a coffee cup, while another person may experience a change in vocal pitch when speaking. The rate which ALS progresses can be quite variable from one person to another. Symptoms can begin in the muscles that control speech and swallowing or in the hands, arms, legs or feet. Not all people with ALS experience the same symptoms or the same sequence or pattern of progression. However, progressive muscle weakness and paralysis are universally experienced. When the breathing muscles become affected, ultimately, people with the disease will need permanent ventilatory support to assist with breathing. Since ALS attacks only motor neurons, the sense of sight, touch, hearing, taste and smell are not affected.

ALS is difficult disease to diagnose. There is no one test or procedure to ultimately establish the diagnosis of ALS. It is through a clinical examination and series of diagnostic tests, often ruling out other diseases that mimic ALS, that a diagnosis can be established. A comprehensive diagnostic workup includes: Electrodiagnostic tests including electromyography (EMG) and nerve conduction velocity (NCV), Blood and urine studies including high resolution serum protein electrophoresis, spinal tap, X-rays, MRI, Myelogram of cervical spine, muscle and/or nerve biopsy etc.

In the context of developing new therapeutic strategies, stem cell therapy is reaching promising results in the treatment of different neurodegenerative disorders. The assumption of this approach is that stem cells, which are able to differentiate into neuronal cells, may replace the degenerated neurons. Moreover, stem cells are able to release different growth factors that may create a microenvironment that promotes neuroprotection. In this regard, different types of stem cells may be used, with mesenchymal stem cells (MSCs) representing a most suitable type. Indeed, MSCs are multipotent, self- renewal stem cells, characterized by an easy accessibility and expandability and all these properties make MSCs a good source of stem cells for cell therapy and regenerative medicine. In addition, being adult stem cells, MSCs do not face the ethical concerns linked to the use of embryonic stem cells.

Breakthroughs in basic research, bioengineering, instrument technology and medical expertise could help in bringing much needed therapeutic options to person with ALS.