Pediatric neurological disorders represent a major part of the disabilities worldwide. In over 10 decades of research to find a cure for these disorders, medical science has not been able to repair the underlying brain injury. This chapter focuses on recent advances in the application of stem cells as a therapeutic tool for some of the common neurodevelopmental disorders (cerebral palsy, autism, intellectual disability and muscular dystrophy). The mechanism of action of stem cells in each disorder has been explained. A review of clinical data has been described giving a clear understanding of current status of stem cell therapy in these disorders. Various factors influencing the outcome of stem cell therapy such as different types of cells, different routes of administration and dosage and frequency of transplantation have also been discussed. Our experience of treating these disorders is exhibited in the form of our published data. Use of novel monitoring tools such as MRI MSK and PET-CT scan brain to track the changes occurring at cellular level after stem cell therapy are described. We also highlight the importance of a multidisciplinary approach of combining rehabilitation with stem cell therapy.
BackgroundThe underlying pathophysiology in intellectual disability (ID) involves abnormalities in dendritic branching and connectivity of the neuronal network. This limits the ability of the brain to process information. Conceptually, cellular therapy through its neurorestorative and neuroregenerative properties can counteract these pathogenetic mechanisms and improve neuronal connectivity. This improved networking should exhibit as clinical efficacy in patients with ID.MethodsTo assess the safety and efficacy of cellular therapy in patients with ID, we conducted an open-label proof-of-concept study from October 2011 to December 2015. Patients were divided into two groups: intervention group (n = 29) and rehabilitation group (n = 29). The intervention group underwent cellular transplantation consisting of intrathecal administration of autologous bone marrow mononuclear cells and standard neurorehabilitation. The rehabilitation group underwent only standard neurorehabilitation.The results of the symptomatic outcomes were compared between the two groups. In the intervention group analysis, the outcome measures used were the intelligence quotient (IQ) and the Wee Functional Independence Measure (Wee-FIM). To compare the pre-intervention and post-intervention results, statistical analysis was done using Wilcoxon’s matched-pairs test for Wee-FIM scores and McNemar’s test for symptomatic improvements and IQ. The effect of age and severity of the disorder were assessed for their impact on the outcome of intervention. Positron emission tomography-computed tomography (PET-CT) brain scan was used as a monitoring tool to study effects of the intervention. Adverse events were monitored for the safety of cellular therapy.ResultsOn symptomatic analysis, greater improvements were seen in the intervention group as compared to the rehabilitation group. In the intervention group, the symptomatic improvements, IQ and Wee-FIM were statistically significant. A significantly better outcome of the intervention was found in the paediatric age group (<18 years) and patients with milder severity of ID. Repeat PET-CT scan in three patients of the intervention group showed improved metabolism in the frontal, parietal cortex, thalamus, mesial temporal structures and cerebellum. No major adverse events were witnessed.ConclusionsCellular transplantation with neurorehabilitation is safe and effective for the treatment of underlying brain deficits in ID.Trial registrationClinicalTrials.gov NCT02245724. Registered 12 September 2014.
Cellular therapy is being actively pursued as a therapeutic modality in many of the neurological diseases. A variety of stem cells from diverse sources have been studied in detail and have been shown to exhibit angiogenetic and immunomodulatory properties in addition to other neuroprotective effects. Published clinical data have shown bone marrow mononuclear cell (BMMNC) injection in neurological disorders is safe and possesses regenerative potential. We illustrate a case of 27-year-old male with traumatic brachial plexus injury, administered with autologous BMMNCs intrathecally and intramuscularly, followed by multidisciplinary rehabilitation. At the follow-up assessment of 3 and 7 months after first cell transplantation, improvements were recorded in muscle strength and movements. Electromyography (EMG) performed after the intervention showed a response in biceps and deltoid muscles suggesting the process of reinnervation at the site of injury. In view of the improvements observed after the treatment, the patient underwent second cell transplantation 8 months after the first transplantation. Muscle wasting had completely stopped with an increase in the muscle girth. No adverse effects were noted. Improvements were maintained for 4 years. A comprehensive randomized study for this type of injury is needed to establish the therapeutic benefits of cellular therapy.
On the Indian Scale for Assessment of Autism (ISAA), his score was 98, while his Childhood Autism Rating Scale (CARS) and Functional Independence Measure (WeeFIM) scores were 28.5 (ASD) and 80, respectively. MRI of the brain and EEG were normal. PET CT scan of the brain revealed hypometabolism in the bilateral cerebellar hemispheres and hypermetabolism in frontal, parietal and temporal lobes. AbstractAutism 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 3months and 7months post intervention, he showed significant symptomatic improvements with no major side effects. At the end of 7months, 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.
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