Abstract

Autism is a complex neurodevelopmental disorder with a worldwide prevalence of 1 in 88. With greater understanding of mechanism of action of cellular therapy it is now possible to address the pathogenesis of autism. Recent findings of cellular therapy offering immunomodulatory, angigogenetic and paracrine effects make it a lucrative option for treatment of autism. We administered a 33 year old adult patient of autism intrathecally, with autologous bone marrow mononuclear cells (BMMNCs), twice with an interval of six months. On follow up at 3, 6 and 9 months post first intervention, he was re-evaluated clinically and no major or minor side effects were observed. At 6 and 9 months objective outcome measures of Indian Scale for Assessment of Autism (ISAA) and Clinical Global Impression (CGI) were used and they showed significant improvement. At the end of 9 months, on ISAA, the score improved from 94 to 64. The CGI showed improvement by change in severity of illness from 3 (Mildly ill) to 1 (Borderline mentally ill). Global improvement on CGI was scored 2 (much improved) with an efficacy index of 5 (moderate therapeutic effect). PET CT scan was repeated at 6 months which showed a balancing effect in the metabolism of affected areas. The changes observed on the PET CT scan correlated with clinical improvements. MRI remained same at 6 months thereby, indicating that PET CT scan may serve as a better monitoring tool for effects of cellular therapy. In this case study, we hypothesize that cellular therapy has repaired the neural connections and achieved balance in the excitatory and inhibitory neuronal cells by various mechanisms of neuroprotection, neuromodulation and neurorestoration. Cell therapy holds great potential and randomized controlled trials may be conducted to study their long term effects in treating autism. Read more...

Abstract

 Autism is a clinically and etiologically heterogeneous disorder characterized by deficits in social interaction, communication, behavior and cognitive skills. The etiological basis of autism still remains poorly understood despite several attempts to decipher its neuropathology from different perspectives. Presently available treatment modalities address only limited autism-associated symptoms and are at best palliative. In this report, we present the case of a 7 year old boy with autism treated with intrathecal administration of autologous bone marrow derived mononuclear cells (BMMNCs). On regular follow ups conducted at 3 and 6 months post-treatment, clinically significant behavioral, social, communication and cognitive improvements were reported. These findings were well supported by objective improvements on the Indian Scale of Assessment of Autism (ISAA), Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) and Pediatric Functional Independence Measure (WeeFIM). The ISAA score improved from 131 to 112, CARS improved significantly from 40.5 (severely autistic) to 32 (mild to moderate autism), along with an improved WeeFIM score from 31 to 36. Severity of illness on CGI (CGI I) changed from 4 (moderately ill) to 3 (mildly ill). Global improvement on CGI (CGI II) was measured at a score of 2 (much improved), along with an efficacy index (CGI III) of 5 showing moderate therapeutic effect. No adverse events were reported throughout the course of the treatment. Through this case report, we demonstrate that treatment with autologous BMMNCs is safe, feasible and has the potential to ameliorate autism.

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Abstract

Autism, the most severe form of autism spectrum disorder (ASD), is a complex neurodevelopmental disorder, characterized by language developmental delay, social skills impairment, communication problems, and restricted, repetitive, and stereotyped patterns of behavior. There is no cure for Autism; hence therapies and behavioral interventions are designed to remedy specific symptoms. We used autologous bone marrow derived mononuclear cells intrathecally in a 14 yr old boy with severe autism to improve the quality of life. At six months, follow up after therapy the general impression on clinical assessment showed mild autism. It is exciting to see symptomatic improvement with shift on Childhood Autism Rating Scale (CARS) from 42.5 (Severely Autistic) to 23.5 (Non Autistic), which was also visualized as enhanced PET scan brain function. All these improvements have led to improved quality of life of the patient as well as the family. Several incurable neurological disorders have shown benefits with cellular therapy thus, autism should be explored as an indication and nuclear imaging can be used to study its effects. Read more...

Abstract

Cellular therapy has been viewed as a novel therapeutic modality for many neurological disorders. Autologous Bone Marrow Mononuclear Cells (BMMNCs) used in many studies, have a safe and ethical profile. These cells have been studied in great depth and have shown angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. These peculiar mechanisms may serve to be beneficial in autism. Recently, hypoperfusion and immune alteration are identified as major underlying pathogenetic mechanisms in autism. We present a case of autism with comorbid mental retardation; treated with intrathecal administration of autologous BMMNCs. Results were documented objectively on Indian Scale for Assessment of Autism (ISAA) and Positron Emission Tomography Computed Tomography (PET CT) scan. On regular follow up assessment of the patient over 18 months, there was significant clinical improvement in social relationship, communication and behavior. On outcome measure, ISAA score improved from 111 (Moderate autism) to 73 (Mild Autism). PET CT scans comparison of pre and post therapy showed balancing effect on brain metabolism. This case provides a great insight into the clinical effects of autologous BMMNCs in autism. Though a case study, the improvements guide us to plan future studies to explore different options of cellular therapy in autism. Read more...

Abstract

Autism is a pervasive developmental disorder affecting socialization, communication and behavior. Neuropathology of autism spectrum disorders is poorly understood and may involve impaired connectivity in the brain, selectively affecting parts of the brain forming circuits supporting social behavior. The currently available treatment options do not address the core neuropathology of autism. Hence, it is important to develop a treatment modality for autism at the earliest. Cell therapy is recently emerging as a potential treatment option for autism. We hypothesize that it may assist in the repair of the disrupted neuronal circuit. The neural repair may take place not only by cellular restoration but also by paracrine and immunomodulatory effects. Cellular therapy has shown promising results for various other neurological disorders. We administered autologous bone marrow mononuclear cells, intrathecally in an 11 year old boy diagnosed with autism. He was assessed for a follow up period of eight months wherein his autistic features had reduced. This was objectively supported by improvement in scores of CARS (31 to 25), ISAA (130 to 98), CGI-I (6 to 5) and FIM (104 to 110). This case study may hint towards exploring cell therapy as a potential treatment alternative for autism, in addition to standard approach. A longer period of follow up along with functional imaging may further help us understand the repair of the impaired neuronal circuit at cellular level. Read more...

Abstract

Cell therapy offers a promising premise in alleviating complex neurological disorders. Autologous bone marrow mononuclear cells (BMMNCs) have been used in many studies and have been documented to have a safe and ethical profile. These cells have shown angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. Precisely, these may serve to address a disorder at a neurophysiological level and thus, hold gratifying results in autism. The literature suggests hypoperfusion and immune alteration as major underlying pathogenetic mechanisms in autism. Herewith, we present a case of autism treated with intrathecal administration of autologous BMMNCs. Results were documented objectively on Indian Scale for Assessment of Autism (ISAA), Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scores and positron emission tomography computerized tomography (PET-CT) scan. On regular follow-up assessment of the patient at 3 mo, at 6 mo (pre 2nd dose) and at 9 mo (i.e., 3 mo post 2nd dose), significant clinical improvement was noted in social relationship, communication and behavior. On the outcome measure, his ISAA score improved from 132 (moderate autism) to 103 (mild autism). On comparison of the PET-CT scan, changes in metabolism correlated with the clinical improvements. On the CGI scores, he showed improvement in all the three domains, with a decrease in the severity of illness and with partial remission of symptoms. This case provides a useful insight into the clinical effects of autologous BMMNCs in autism and guides us to plan future studies and offers a promising premise in alleviating complex neurological disorders.  Read more...

Abstract

Adults with autism spectrum disorder (ASD) experience significant impairments in social interaction, poor planning, decision making, timing and motor skills which impact on their daily activities of living and ability to access the health care services. Early research on ASD primarily focused on children with service provision for adults is still in its infancy. The current treatment for adults with ASD is complex, considering the diverse etiology and characteristics. In this study, a 25-year-old male diagnosed with ASD at the age of 7 years underwent intrathecal autologous bone marrow derived mononuclear cells (BMMNCs) administration, followed by neurorehabilitation. Following six months of cell therapy, the patient showed improvement in concentration, attention, command following, sitting tolerance, social interactions, eye contact, and memory. His Childhood Autism Rating Scale (CARS), Indian Scale of Assessment of Autism (ISAA), Functional Independence Measure (FIM) scores improved from 36 to 34, 87 to 78, and 65 to 78, respectively. As compared to pre-intervention, brain F-FDG PET/CT scan showed improvement in supramarginal gyrus, thalamus, basal ganglia, medial temporal cortex and cerebellum. This study suggests the efficacy of autologous BMMNCs in addressing the core 18 neurodeficits of adult ASD, and thereby improving the quality of life.  Read more...

Abstract

AAutism is a very complex neurodevelopmental disorder. Different researchers have tried understanding the basic pathophysiology of autism. It is understood now, that the neural hypoperfusion and immune dysregulation are the two key pathologies associated with Autism. There is reduced blood flow to certain specific areas of the brain (mesial temporal and cerebellum), which in turn could be the cause of reduced functioning in these areas. This coupled with an overall imbalance in the activity of the brain, is possibly responsible for the manifestations associated with autism. Based on the above understanding, many scientists all over the world, such as, Ichim et al from USA and Siniscalco from Italy (in various scientific reviews and publications) have strongly emphasized the potential of stem cells for the treatment of autism. These proposals are in view of the fact that stem cells have strong angiogenic potential which could facilitate counteractive processes of improving perfusion and balancing inflammation by immune regulation which would exhibit beneficial clinical effects in patients with autism.  Read more...

Abstract

2‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography‐computed tomography scan was performed on 45 children with autism to study the baseline pattern and age‐related developmental changes in the brain metabolism. Median standardized uptake values (SUVs) were compared with published healthy control data. Results showed that, in contrary to control data, the median SUVs in children with autism decrease linearly with increase in age. As compared to controls, autism children below 5 years showed greater metabolism and older children showed lower metabolism. In autism group, comparison of absolute SUVs within different regions of the brain revealed relatively lower metabolism in amygdala, hippocampus, parahippocampal gyrus, caudate nucleus, cerebellum, mesial temporal lobe, thalamus, superior and middle temporal pole, and higher metabolic uptake in calcarine fissure and Heschl’s gyrus. These results help in understanding the baseline metabolism and developmental changes of brain among different age groups in autism. Read more...

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder affecting communication, behavior and socialization. The exact etiology is unknown, but combination of genetic, environmental, and immunological f actors is likely to be responsible for ASD. Autologous bone marrow mononuclear cells (BMMNCs) have been studied in great detail and have a safe, feasible and ethical profile. In this study, we present the case of a 4 year old boy with ASD who underwent intrathecal administration of autologous BMMNCs. After 8 months follow up, significant social, behavioral and communication improvements were observed. A comparative PET CT scan performed before and 8 months after the intervention revealed improvement in metabolism of frontal lobe, parietal lobe, medial temporal lobe (bilateral hippocampi and amygdale), bilateral cerebellar hemispheres when compared to previous brain scan. The score on Indian Scale for Assessment of Autism (ISAA) reduced from 114 (moderate aut ism) to 99 (mild autism), Indian Scale for Assessment of Autism (CARS) score improved from 35.9 to 28.5, Wee Functional Independence Measures (WeeFIM) score improved from 51 to 56. Severity of illness score on Clinical Global Impression CGI reduced from 4 (moderately ill) to 3 (mildly ill), Global improvement on (CGI) scale graded him with a score of 2 (much improved) and efficacy index on CGI showed moderate therapeutic effect. Read more...

Abstract

Autism is a complex neurodevelopmental disorder defined by a triad of deficits including impaired social interaction, communication and behaviour. With greater understanding of mechanism of action of cellular therapy it is now possible to address the pathology of autism. Here is a case of a six and a half year old boy with autism who was administered autologous bone marrow mononuclear cells (BMMNCs) intrathecally followed by an intensive rehabilitation program. On follow up at 3 months and 7 months post intervention, he showed significant symptomatic improvements with no major side effects. At the end of 7 months, ISAA score improved from 98 to 81. The Wee FIM showed improvement 80 to 89.1. CARS score reduced from 28.5 (mild to moderate autism) to 23.5 (mild autism). PET CT scan of the brain performed pre intervention and seven months post showed a balancing effect in the metabolism of affected areas. It also showed reduction in hypermetabolism of the frontal, parietal and temporal lobe bilaterally and increase in metabolism of the previously hypometabolic bilateral cerebelli. The changes observed on the PET CT scan of the brain correlated with clinical improvements. We hypothesize that cellular therapy holds great potential as a treatment modality for autism in combination with standard rehabilitation therapy. Randomized controlled trials are warranted to study their long term effects in treating autism. Read more...

Abstract

PET- CT scan has been recently utilized to detect functional abnormalities in the brain. In autism, the MRI of brain is normal hence, functional neuroimaging techniques such as Positron Emission Tomography - Computer Tomography scan of the brain should be explored. Autism is a complex neurodevelopmental disorder affecting communication, behavior and socialization. Currently, available therapeutic approaches are aimed at symptomatic changes and do not target the core pathology in the brain of autism. Cell therapy has recently emerged as a promising treatment modality for autism. However, the effects of cell therapy need to be monitored by objective imaging. In this study, we present the case of a 6 year old boy with autism treated with intrathecal administration of autologous bone marrow mononuclear cells and monitored with Positron Emission Tomography - Computer Tomography scan. On regular follow up at 3 and 6 months, significant social, behavioral and communication improvements were observed. On outcome measures, the Indian Scale for Assessment of Autism score pre intervention improved from 113 to 97, Functional Independence Measure improved significantly from 42 to 50 and Childhood Autism Rating Scale improved from 42.5 to 35.5. The severity of illness on Clinical Global Impression scale showed a change from a score of 5 (markedly ill) to 4 (moderately ill). Global improvement graded on the CGI scale was 2 (much improved). The efficacy index on Childhood Autism Rating Scale showed moderate therapeutic effect (score 5). Interestingly, Positron Emission Tomography - Computer Tomography comparisons at 6 months revealed improved metabolism of the previously hypometabolic areas of the brain which correlated well with clinical improvements. No adverse events were reported. Read more...