Motor Neuron Diseases (MND) are marked by the deterioration of motor neurons or nerve cells that connect the brain and the rest of the body. Amyotrophic lateral sclerosis (ALS) is the most prevalent manifestation of MND. It impacts both upper and lower motor neurons, which impair involuntary or autonomic functions. It progressively weakens the muscles and compromises limb movement, speech, swallowing ability, bladder or bowel control, and lung function. Decline in lung function is often the cause of mortality in ALS.
ALS medications emphasize slowing the progression of symptoms rather than treating the pathways behind the disorder. The improvement in overall survival with the current treatment modalities is modest at best. Moreover, their intake is also associated with adverse effects. Stem cell treatment for ALS addresses these limitations by targeting the mechanisms of the disorder and improving functions instead of merely delaying its progression.
Mechanisms Behind ALS
Scientists have been exploring the pathways behind the development and progression of ALS. Although their understanding is still incomplete, research has proved the disorder to arise from genetic and environmental factors, termed familial and sporadic, respectively. The impact of genetic mutations reflects in the pathological pathways in cells, including DNA repair, protein misfolding, protein aggregation, mitochondrial dysfunction, etc. It leads to significant cell damage, which eventually results in wasting of muscles linked to these neurons. Cell damage also triggers inflammation, activating and recruiting immune cells, aggravating the condition.
Over 40 genes contribute to ALS, with FUS, SOD1, C9orf72, and TDP43 the most prominent among them. Environmental exposures also correlate to risk of disease development and short survival period. The complex interplay between environment and genetic mutations requires ALS Treatment Options which can act on the dysfunctional cellular pathways and prevent neural damage.
Stem Cell Treatment for ALS
The therapeutic use of stem cells have been bolstered by their amazing capacity to restore damaged tissue. Their use for ALS is encouraged by the favorable results they have had in a variety of neurological illnesses. They can develop into nerve cells that are able to operate. Research has demonstrated that stem cells for MND in animal models have the following effects:
- These cells increase the expression of factors such as NGF, BDNF, GDNF, VEGF, IGF1, and NT3, which protect neural cells from damage.
- They also overexpress signaling pathways like pAkt, PGC-1α, p-CREB, etc., enhancing nerve cell survival.
- Stem cells augment the levels of anti-inflammatory mediators such as TGF1, IL10, IL13, etc., while reducing the pro-inflammatory cytokines.
Through these pathways, stem cells modify the microenvironment and eliminate the detrimental factors to prolong cell survival. In animals, stem cells have mitigated neural loss, muscle weakness, and immune system activation. It resulted in improved motor functions and prolonged survival.
Clinical Evidence
The positive outcomes in animals have promoted the evaluation of stem cells in clinical trials. Since 2003, clinical studies on mesenchymal stem cells (MSCs) have been conducted.
A 2006 study by Mazzini et al. reported improvements in lung function and performance of daily activities in 5 out of 9 patients after administering stem cells.
Barzewska et al. administered MSCs in 67 patients. The trial showed a 70% decrease in the risk of death and a two-fold increase in survival of the MSC-treated group.
Analysis of blood samples of patients after the treatment revealed that stem cells decreased immune system activation and elevated the quantity of regulatory T lymphocytes, which modulated the immune response in ALS.
Is Stem Cell Treatment Safe?
The adverse effects of stem cell therapy have been a primary concern for many. Therefore, several clinical trials have focused on assessing the safety of stem cell treatment in ALS. The first clinical trial that analyzed the adverse effects of stem cells in ALS was in the year 2003 and demonstrated that the therapy is well-tolerated in all patients. The author, Mazzini et al., again performed a long-term safety study spanning 9 years. The 19 patients of the study received MSCs and showed no indications of tumor formation or any other complications in the follow-up period of the study. Many other clinical trials have documented similar results. Such reports imply that MSC treatment is potentially safe and has no negative impact.
How close are we?
The analysis of the application of regenerative medicine for ALS has been gaining momentum, considering its short survival period. After years of research, many companies are on the verge of finalizing the stem cell-based products for ALS.
CorestemChemon, a biotechnology company in South Korea, has developed NeuroNata-R- an MSC-based product for ALS treatment. South Korea, the USA, and Europe have designated it as an orphan drug. In addition to offering regulatory help, the designation expedites the medication review process. Clinical trials for the product are now in phase three. According to the trial’s preliminary findings, clearance is anticipated by the end of 2026.
NurOwn, another MSC-based product created by BrainStorm Cell Therapeutics, has been approved for Phase 3b of the clinical trial. It has shown significant delay in rate of disease progression and improvements in functional score with 90% ALS patients surviving for five to seven years survival in 90% people.
These therapeutics are sparking hope that Stem Cell Treatment for ALS is not only effective but also safe. Soon, they will be approved for use in hospital settings.
MND Cure Research
To improve the potential of stem cells for treating MND or ALS, scientists are devising new strategies. One of them is the genetic engineering of stem cells to produce more neuroprotective factors. Such engineered MSCs together with mononuclear cells prolonged survival in mice. Umbilical cord MSCs genetically modified to produce GDNF, NCAM and VEGF mitigated symptoms and increased life span in animals. Another study by Wang et al. genetically edited neurons derived from umbilical cord MSCs to secrete BDNF. These neurons prolonged survival and enhanced motor neuron performance in animals.
Conclusion
The progressive nature of ALS, accompanied by the absence of a cure, leads to a shorter life span of patients and diminished quality of life. The dysfunction of multiple cellular pathways and involvement of diverse biological processes demand a therapy that can act in a holistic manner. Stem cell therapy has shown potential in ALS. It not only delays the progression of the disease but also improves the functional scores of patients.
The trials have proved the safety and effectiveness of stem cell therapy for ALS. These efforts are finally culminating in the phase 3 trials of two MSC-based products for ALS. They are in their last phase of testing and will soon be included in the mainstream treatment. Advancells have been tapping the potential of Regenerative Medicine for ALS by delivering MSCs for therapies. The team at Advancells meticulously tests each product through high-throughput assays to provide only the premium-quality cells.
FAQ’s
Q- How is stem cell therapy for ALS better than the current treatment options?
Present treatment modalities only act on one specific cellular pathway to delay the progression, whereas stem cells target all the dysfunctional mechanisms to improve function and prolong survival.
Q- How many sessions of stem cell therapy for ALS are required?
Clinical trials have varied in the number of sessions and stem cell dose. Additionally, the administration of stem cells also depends on individual factors such as comorbidities, disease severity, etc. Therefore, the final number of sessions can only be defined based on the patient’s details.
Q- Which stem cells are used for ALS treatment?
Different stem cell types have been evaluated for their effects on ALS. MSCs have gained preference over other cell types and shown substantial improvements in ALS patients. Two MSC-based products are close to receiving approval for ALS treatment.
Q- Is stem cell therapy safe?
Several clinical trials have estimated the effectiveness and safety of the stem cell treatment for ALS. The effectiveness of the therapy differed with several variables in the studies, including the cell dose, administration route, source of cells, etc. However, each study reported that the therapy did not cause any complications.
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