ALS treatment using umbilical cord stem cells
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration of motor neurons in the brain and spinal cord. The condition progresses slowly, starting with muscle weakness in the limbs and ending in paralysis and death, mainly because of respiratory failure. The disease is a significant burden for society. ALS affects approximately 1 to 4 individuals per 100,000 people [1,2]. Mortality usually occurs within 3 to 5 years from the appearance of the first symptoms. About 50% of patients die within 30 months of symptom onset, 20% of patients survive five years, and up to 10% survive ten years from symptom onset [3,4]. Even though researchers have discovered many causes of the disease (glutamate excitotoxicity, glial cell dysfunction, dysmyelination, immune/inflammatory responses), finding an effective therapy to treat ALS remains a significant challenge.
Only two ALS adjuvants, riluzole and edaravone, have been approved by the US Food and Drug Administration (FDA), and those two drugs only modestly improve survival and disease progression [5]. Researchers have launched several early-phase clinical trials to evaluate the potential of stem cells in treating ALS. Fundamental advances from early-phase clinical trials of stem cell therapy for ALS are identifying promising pathways and key challenges in applying stem cell therapy for ALS.
Stem cell therapy has recently become a focus of both preclinical and clinical research in ALS. Stem cells have multifunctional characteristics that allow them to target multiple pathogenic mechanisms in ALS, which is why they have recently become a focus of both preclinical and clinical research. However, researchers have not yet fully explained their underlying mechanisms. There are no treatments that can cure or reverse this disease. There is a need for therapies that can slow down the disease’s progress, cure, or reverse ALS. Stem cells may solve, maintain, and nourish diseased motor neurons.
Stem cell (MSC) therapy in the treatment of ALS
ALS is a fatal disease that has a significant impact on patients and caregivers, so finding an effective treatment for ALS is essential [6,7]. Clinical trials with stem cell therapy in humans are still in the early stages of development. Researchers must ensure that they conduct well-controlled clinical trials to determine the optimal treatment intervals, the ideal cell type, cell dose, and location and method of stem cell infusion.
Cell therapy focuses on replacing degenerative motor neurons. However, this is also a significant challenge because of the complexity of the pathology and the anatomical distribution of degenerative sites. I have made research hypotheses that using MSCs for infusion may exert a beneficial role by releasing neurotrophic factors, immunomodulatory, anti-inflammatory, anti-apoptotic activity, tissue repair, and regeneration [8]. In addition, MSCs have an important property called ‘homing’ – the ability to migrate into the injury site and then secrete bioactive factors to regulate immune and trophic functions at the site [9,10].
Researchers tested a variety of injection methods, including spinal infusion, intravenous injection, and intramuscular injection. Transplanted human MSCs have shown positive results in delaying the onset and progression of ALS through the production of neurotrophic factors and reduction of neuroinflammation [11, 12]. Phase 1 and 2 clinical trials using these cells showed promising results in slowing the rate of disease progression [13], and a phase 3 clinical trial with a larger sample size of patients is underway (ClinicalTrials.gov: NCT03280056). Two other trials registered on ClinicalTrials.gov for Phase 1 and 2 clinical trials are currently evaluating the efficacy of using autologous adipose MSCs in patients with ALS in Spain (NCT02290886) and the United States (NCT03268603). The primary outcome of both studies was to assess safety by measuring the number of adverse or serious events.
Safety of umbilical cord stem cell infusion in ALS therapy.
MSCs have been promising in the treatment of ALS. They infused patients with doses to confirm the safety of umbilical cord stem cell infusion in ALS therapy (ClinicalTrials.gov: NCT02881476). No significant adverse events occurred. Patients with ALS showed good tolerance to intrathecal injection of umbilical cord stem cells, as shown by this outcome. This study confirms the safety of injecting umbilical cord stem cells into patients with ALS. There were no serious adverse events recorded in the study.
Conclusion
Among treatments for ALS currently being researched, stem cell therapy shows many pros. These cells possess the ability to provide pleiotropic immunomodulatory and protective effects on host cells simultaneously. In humans, although still in research, initial clinical trials of stem cell therapy for ALS have made great strides in determining safety. The important thing now is to determine the effectiveness of treatment and determine the most effective source of stem cells, cell dosage, location, and safe infusion method. However, to ensure safety when transmitting stem cells, we still need the advancement of science and technology.
Innovative imaging techniques and stem cell delivery methods will minimize patient risks by determining the optimal location with minimal disruption to surrounding tissues. Such technological advances will lead to fewer side effects and provide a more accurate interpretation of treatment effectiveness. In addition, it is still necessary to diagnose ALS early to get the best results of stem cell therapy.
Reference
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