Abstract

Intellectual Disability is a non progressive developmental condition which significantly affects cognition, learning and adaptive behavior of an individual. Currently, there is no treatment available for intellectual disability. However, the therapies available focus mainly on the symptoms of the patient and do not address its core neuropathology. Neurorestorative strategies such as cellular therapy may benefit in these disorders. To study the effect of cellular therapy in intellectual disability, we administered a 13 year old boy with autologous bone marrow mononuclear cells, intrathecally. As a part of the protocol, he was also put on a personalized rehabilitation program. Follow up was done at 3 months and 6 months. No major adverse events were recorded post intervention. In a period of 6 months, he showed improved eye contact, cognition, learning ability, behavior and ability to perform activities of daily living. His score on Functional Independence Measure increased from 67 to 76. On comparing the pre and post PET CT scan, improvement in metabolic activity of hippocampus, left amygdala and cerebellum was recorded. These changes correlated to the functional outcome. These changes suggest that cellular therapy in combination with rehabilitation may repair the neuronal networks in intellectual disability, hence improving processing of information. It was found to be a safe and effective therapeutic modality. Hence, cellular therapy may provide hope for patients and caregivers to improve their quality of life. Read more...

Abstract

Background: The 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.

Methods: To assess the safety and efficacy of cellular therapy in patients with ID,we conducte danopen-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 tomographycomputed 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.

Results: On 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.

Conclusions: Cellular transplantation with neurorehabilitation is safe and effective for the treatment of underlying brain

deficits in ID. Read more...

Abstract

Intellectual Disability (ID) is a developmental disability characterized by sub average intellectual functioning, occurring in 2-3% of the population. The underlying cause in ID is the sub-functioning of the neurons which significantly affects cognition, learning and adaptive behavior of an individual. The conventional management strategies address specific symptoms observed in ID and not the core pathology. In this case study, we evaluated the symptomatic and functional improvements after intrathecal transplantation of autologous Bone Marrow Mononuclear Cells (BMMNCs) in a 13-yearold girl diagnosed with ID. As a part of the protocol, she was also put on a multidisciplinary rehabilitation program. She underwent two cellular therapies twice at an interval of 11 months. Follow up was done at regular intervals of four and eleven months after each cellular therapy. No major adverse events were recorded post intervention. Improvements in command following, eye contact, sitting tolerance, balance, aggressive behaviour, hyperactivity and clarity of speech were observed over a period of 30 months of first intervention. Functional Independence Score (FIM) score increased from 76 to 78. On comparison of pre-intervention and post intervention after 11 months PET CT scan, improvement in metabolic activity of frontal lobe, cerebellum and the mesial temporal structures was recorded. These objective changes suggest that cellular therapy in combination with rehabilitation improves neuronal functioning, hence improving processing of information in ID. However, larger randomized control studies will be required to demonstrate long term benefits of cellular transplantation in ID. Read more...