Neuroregenerative-Rehabilitative Therapy for Spinal Cord Injury

Spinal cord injury is one of the leading causes of disability worldwide. Current mainstay treatment strategies consist of surgical and medical management in acute and subacute stage. Rehabilitative management in the chronic stage. None of the existing strategies can repair the damage to the spinal cord and recover neurological functioning. Stem cells have promising results in pre-clinical and clinical studies. Various pre-clinical studies have evidenced neuro-regenerative capabilities of stem cells and shown neural recovery. Clinical studies have also shown improvements in neurological functions and quality of life. This chapter discusses about different types of cells available, routes of administration available to transplant these cells, dosages of cell and optimum time after injury at which cells should be transplanted based on world-wide literature. We have also discussed results following our protocol of intrathecal transplantation of autologous bone marrow mononuclear cells. Although, not a cure, stem cell therapy further improves quality of life, functional independence and reduces secondary complications when combined with existing treatment strategies; neuroregenerative rehabilitative therapy

Stem Cell Therapy in Pediatric Neurological Disabilities

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

Stem Cell Therapy in Motor Neuron Disease

Motor neuron disease (MND) is an insidious, fatal disorder that progresses with the selective loss of anterior horn cells of the spinal column. Over 150 years since it was first described, various therapeutic approaches have been tested in the quest of a cure but with little success. Current standard therapy only improves lifespan by a few months; palliative care is the only option available for patients. Stem cell therapy is a potent approach for the treatment of this devastating disease. A multitude of vitalizing effects, both paracrine and somatic, a robust safety profile, as well as ease of availability make a strong case for using these cells for therapeutic purposes. Coupled with rigorous rehabilitation, this powerful treatment modality has been shown to slow disease progression, improve quality of life, and increase survival, along with being well tolerated by amyotrophic lateral sclerosis (ALS)/MND patients. Compelling preclinical as well as clinical evidence abounds that stem cells hold great potential as a therapy for ALS/MND. Although not a definitive solution yet, stem cells have been verified to have slowed and/or halted disease progression in a subset of ALS/MND patients

Cell Therapy for Muscular Dystrophy

Muscular dystrophy is a major unmet medical need associated with an inevitable progressive muscle damage and loss of function. Currently, treatment is only symptomatic and supportive. This chapter focuses on cell therapy as a potential treatment approach for muscular dystrophy. Mechanism of action of cell therapy and its ability to alter disease pathology have been discussed. A review of preclinical and clinical studies has been presented with the advantages and shortcomings of various cell types. Rationale for our treatment protocol and experience of treating muscular dystrophy patients has been discussed. Our published results have shown the efficacy of the intrathecal and intramuscular administration of autologous bone marrow mononuclear cells in different types of muscular dystrophy patients. The scores on outcome measures such as 6-minute walk distance, North star ambulatory assessment, Brooke and Vignose scale, Functional independence measure, and manual muscle testing either improved or were maintained suggestive of slowing down disease progression. Efficacy and safety of the treatment was also studied using comparative MRI-MSK and EMG showing decreased fatty infiltration in various muscles post-cellular therapy. Thus, it was found that autologous BMMNC transplantation is a safe and effective treatment option and improves the quality of life of MD patients

Cellular Transplantation Alters the Disease Progression in Becker’s Muscular Dystrophy

Becker’s Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council’s Manual Muscle Testing (mMRC-MMT). Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL). Functional Independence Measure (FIM) score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation

Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow Mononuclear Cell Transplantation

Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child’s development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve conduction. Cell therapy is being explored as an alternate therapeutic strategy as there is no treatment currently available for CP. To study the benefits of this treatment we have administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand functions, walking stability, balance, posture and coordination improved. His ability to perform activities of daily living improved. On repeating the Functional Independence Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography- computed tomography (PET-CT) scan of the brain six months after intervention showed progression of the mean standard deviation values towards normalization which correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a potential for treatment of CP

Stem Cell Therapy for Learning Disability

Learning disabilities (LDs) are caused by genetic and/or neurological factors that alter brain functioning and affect processes related to learning, which include dyslexia, dysgraphia, and dyscalculia. It hinders the child’s academic, social, and overall life skills. Current treatments for LD include medication and rehabilitation, focusing on management of symptoms. Thus, there is a need to explore newer treatments which will work at cellular level. Stem cell therapy is an evolving field of regenerative medicine and has shown great potential as a treatment strategy for various neuro-developmental and neurological disorders. It addresses the core underlying pathology and its benefits are enhanced when combined with standard treatments. This chapter focuses on various aspects of stem cell therapy in LD which includes the basics of stem cell therapy, rationale for use of stem cells, mechanism of action, monitoring tools like PET CT scan, and multidisciplinary rehabilitation. We have also enumerated our clinical experience and results of patients who underwent autologous bone marrow mononuclear cell transplantation combined with extensive rehabilitation. These patients showed a positive outcome, without any major adverse events. Nineteen out of 20 patients showed improvement in reading, writing, mathematical skills, attention, memory, problem-solving, comprehension skills, spelling, vocabulary, and overall increased academic performance

Positron Emission Tomography—Computer Tomography Scan Used as a Monitoring Tool Following Cellular Therapy in Cerebral Palsy and Mental Retardation—A Case Report

Cerebral palsy (CP) is one of the non-progressive neurological diseases caused by damage to the brain tissue at birth, which leads to physical, cognitive and perceptive symptoms. Even after lifelong medical and therapeutic management there are residual deficits which affect the quality of life of the patients and their families. We examined a maximally rehabilitated, 20 year old male suffering from CP and Mental Retardation (MR). He had diplegic gait and Intelligence Quotient (IQ) score of 44 with affected fine motor activities, balance, speech and higher functions. Positron Emission Tomography—Computer Tomography (PET-CT) scan identified frontal, temporal, parietal, occipital, left cerebellar lobes, amygdala, hippocampus, and parahippocampus as the affected areas. He was treated with cellular therapy of Autologous Bone Marrow Derived Mono-Nuclear Cells (MNCs) transplantation followed by multidisciplinary rehabilitation. Six months following therapy, PET-CT scan showed significant increase in metabolic activity in all four lobes, mesial temporal structures and left cerebellar hemisphere, also supported by clinical improvement in IQ, social behavior, speech, balance and daily functioning. These findings provide preliminary evidence to support the efficacy of cellular therapy for the treatment of CP with MR. PET-CT scan can also be viewed as an impressive tool to monitor the effects of cellular therapy