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Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) / ALS Stem Cell Treatment:

Amyotrophic Lateral Sclerosis (ALS) / ALS stem cell treatment

is a fatal neurodegenerative disease characterized by progressive degeneration of upper motor neurons in the cerebral cortex and lower motor neurons in medulla and anterior horn of spinal cord. It has a poor prognosis with life expectancy of 3 to 5 years since onset of the disease in western countries. The disease selectively affects motor neurons sparing the sensory system. The etiology of the disease poorly understood and several evidential theories fail to determine the exact cause. NeuroCyte Stem Cell Center provide best ALS Stem Cell Treatment in Bangalore, India.

Disease presentation is a mixture of both UMN and LMN signs and symptoms. It manifests as progressive muscle weakness which begins in either limbs or bulbar regions and slowly spreads to other regions. The eventual fatality due to the disease is caused by weakness of the respiratory muscles and respiratory insufficiency. Some of the other symptoms of the disease are cramps and fasciculations present in multiple regions of the body, emotional disturbances, dysarthria, dysphagia, fatigue and spasticity.

Reflexes may be exaggerated and Hoffmann’s sign may also be positive. There are various presentations of the disease and the prognosis of the diseases is worse with bulbar onset, old age, presence of LMN features, low forced vital capacity (FVC) and low scores on revised ALS- functional rating scale (ALSFRSr).

ALS presents with variable clinical features which may appear similar to many other UMN and LMN diseases and hence to better categorize these patients revised El-escorial criteria are used. According to these patients are categorized into definite ALS, probable ALS and possible ALS. Diagnosis of definite ALS is made upon presence of both UMN and LMN symptoms in more than one body regions and/or elemyographic evidence of anterior horn involvement. ALS significantly hampers the quality of life of patients due to increased dependence for performing activities of daily living as the disease progresses. If anyone is looking for getting best ALS Stem Cell Treatment then this would be the right place to consult for.

Currently, there is no cure for ALS. A multi disciplinary management is the best approach for ALS Stem Cell Treatment. This includes pharmacological intervention, rehabilitation, artificial ventilator support in the later stages of the disease, Percutaneous endoscopic gastrotomy (PEG) preventing dysphagia related complications, etc. 

Unmet medical needs 

Because of the rapid progression and unknown etiology, ALS remains undefeated. All the conventional treatments available manage the symptoms and associated conditions, failing to address the core pathology of ALS. 

Stem cell therapy for ALS 

Stem cell transplantation is an attractive management strategy for ALS. Various types of cells, routes of administration and different protocols of administration are being studies widely world over. The safety of autologous stem cell transplantation has been established. 

Marked progressive axonal degeneration of motor neurons in the spinal cord and motor cortex is noted in ALS. Multitude of mechanisms, have been thought to contribute. Non-neuronal glial cell and astrocyte involvement is also suggested in some studies. Up regulation of superoxide dismutase causes cascade of events and thereby oxidative stress. Whereas upregulation of glutamate cause excitotoxicity. Autoimmunity and widespread neuroinflammation are also stipulated contributors to the pathophysiology of ALS.

Replacement of degenerated motor neurons due to these causal factors is the ultimate goal of transplantation therapy but various factors influence the outcome of the transplanted cells. Survival of the cells in the host environment, their neurogenic potential, actual neurogenesis at the target site and formation of neuronal connections over long distances are some of the factors. As the transplantation science evolves these factors could be monitored to gain appropriate outcome but currently the aim of transplantation is to protect the existing motor neurons and attempt to bring out regeneration and repair in the damaged motor neurons.

Although stem cells have neurogenic potential their fate is dependent on various factors. They have a neurotrophic influence on the nervous system and can home onto the site of injury. They further demonstrate immomodulatory, anti-inflammatory and cytoprotective properties. The factors secreted by these cells bring about neoangiogenesis. These paracrine effects lead to neuroprotection and subsequent alteration in the disease course and progression. 

Animal Studies 

The pre-clinical animal studies have shown benefits in the motor function. Human clinical trials are currently being undertaken. Safety of allogenic cells is also being studied and for the use of manipulated allogenic cells strict laboratory guidelines and clinical protocols must be followed. 

Human studies 

Frontal motor cortex transplantation suggested significant increase in survival. However the procedure of administration is extremely complex and can be performed only by a skilled surgeon. 

Intra-spinal transplantation post laminectomy at the level of C1-C2 showed functional recovery of respiratory function, muscle strength and bulbar impairment. Another trial with spinal transplantation arrested the drop in the respiratory function and improvement on neurological scales. Intra-spinal administration also showed neurotrophic effect and preservation of existing neurons. 

Intrathecal transplantation was found to reduce the rate of progression of the disease and drop in the ALS-FRS scores. 

Due to lack of comparative studies between the routes of administration, the evidence for best route of administration remains scarce. 

A phase I safety trial conducted by Mazzini et al. 2010 showed that autologous mesenchymal stem cells are safe to use for the treatment of ALS. The cells were injected intraspinally at the thoracic level and motor function improvement was observed. 

Karussis et al. 2010 conducted a safety and efficacy trial with intrathecal and intravenous administration of autologous mesenchymal stem cells in 19 patients of ALS. These patients were followed up for 25 months. This trial reiterated the safety of autologous mesenchymal stem cells and also showed the immunomodulatory effects of MSCs in ALS. 

A long-term safety study with a follow up of over 9 years by Mazzini et al. 2012 showed that the treatment with autologous mesenchymal stem cells was safe.

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