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Autism spectrum disorders (ASD)

Stem Cell Treatment For Cerebral Palsy

Autism Stem Cell Treatment for Autism spectrum disorders (ASD):

Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by impairments or delays in social interaction, communication and language along with repetitive behavior. A report by the Surgeon General, states that autism has roots in both structural brain abnormalities and genetic predispositions. They are called spectrum disorders because of the wide range of severity of symptoms. The prevalence of autism has increased radically over the few decades for reasons not yet known. It is seen three to four times more in boys than girls. 

ASD is associated with known genetic causes in 10-15% of cases. The exact etiology and pathophysiology of autism remains poorly understood. The numerous biochemical abnormalities detected in autism are oxidative stress; endoplasmic reticulum stress; mitochondrial dysfunction; decreased methylation; underproduction of glutathione; intestinal dysbiosis and toxic metal burden. The environmental factors like organophosphates and heavy metals are also attributed to the origin of the disease. Brain hypoperfusion and immune dysfunctions have been postulated as the two main underlying pathologies in autism. The degree of hypoperfusion is proportional to the severity of the symptoms of autism. The extent of hypoxia was shown to be inversely correlated to Intelligent Quotient (IQ). 

A range of findings have suggested autism as a disorder of growth of the neural systems and connections, likely to be responsible for the under development of functions such as communication, behavior and socialization. Utah and Chris Frith (2010) proposed a social brain hypothesis to explain theory of mind deficits in ASD. The social brain concept tries to localize the complex social perception to superior temporal sulcus (STS), amygdala, orbital frontal cortex (OFC), and fusiform gyrus (FFG). The key roles implicated are STS region in analysis of perception, FFG in face detection and recognition, OFC in social reinforcement and reward processes, the amygdala in analysis and regulation of emotions. These areas form neural interconnections to establish a pathway from perception to action.  

Autism, similar to other neurodevelopmental disorders, is incurable and requires chronic management. Currently, the only treatment options available for autism are behavioral, nutritional and medical intervention. These interventions facilitate development and learning, promoting socialization, self awareness, reducing maladaptive behaviors and educating and supporting families. 

Unmet medical needs 

Like other complex neurodevelopmental disorders, ASD is thought to be the final common pathway of multiple etiological and neuropathological mechanisms, thus, complicating the search for autism-specific biological markers. As there are no definitive biological markers, diagnosis relies on the recognition of an array of behavioral symptoms that vary from case to case, heterogeneous and overlap with other childhood neuropsychiatric disorders. The treatment available does not address the core pathology of autism but only manages the symptoms and associated medical conditions.  

Autism Stem Cell Treatment

Stem cell therapy is emerging as one of the treatment strategies for autism. It has the therapeutic potential to repair the damaged neural tissue at molecular, structural and functional level. They are known to address the underlying core neuropathology of autism viz. Hypoperfusion and immune dysregulation via neuroprotection, neuromodulation and neurorestoration. Hypoperfusion results in hypoxia. Reversal of hypoxia may lead to self repair and neural proliferation, which is observed in many animal models of cerebral ischemia. In cerebral ischemia animal models, bone marrow stem cells have shown to repair the ischemia-damaged neural networks and restore the lost neuronal connections. Hence, stem cells may be used to stimulate angiogenesis and lead to reperfusion. These cells also secrete several biomolecules with anti-inflammatory properties through paracrine effect. This tries to maintain equilibrium in the immune system alterations and activate endogenous repair mechanisms in autism. Thus, stem cells are capable of suppressing the pathological immune responses as well as stimulating neovascularisation. Cell therapy may also prove useful for the treatment of T cell defect associated with autism. 

Not many preclinical and clinical trials have been conducted till date to study the benefits of stem cell therapy in autism. It is very challenging to study the effect of any intervention on animal models of autism due to lack of characteristic social interaction and language deficits found in autism. There are some case reports and case series which are recently published and have shown beneficial effects of cellular therapy. 

Sharma et al published the first clinical study which was an open label proof of concept study in 32 patients of autism. The results of their trial demonstrated the safety and efficacy of stem cell therapy for autism. They administered autologous bone marrow mononuclear cells intrathecally. These patients showed improved neurological functions which were recorded on objective scales such as ISAA and CGI and also the improvement in brain metabolism was observed in PET CT scans of few patients.

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