Clinical translation of the benefits of cell transplantation in a case of cerebral palsy

Abstract

Aims: Cerebral palsy (CP) is an umbrella term including a group of permanent disorders of development of movement and of posture causing activity limitation. Oxidative stress and glutamate mediated excitotoxicity are important mechanisms of injury to both the white matter and neurons in the developing brain resulting in motor deficits. No treatment measures are available that can repair the existing damage. Use of bone marrow stem cells for the treatment of CP has shown promise owing to their capacity for self-renewal, differentiation with a potential of neuroregeneration and secretory paracrine effects. Methods: To study the efficacy of cell transplantation in CP, we administered autologous bone marrow mononuclear cells intrathecally to a 2.2-year-old female patient. She was followed up at 9 months and a repeat transplantation was administered. A second follow up was done 5 months after second transplantation. Gross Motor Function Classification System-Expanded & Revised (GMFCS-E&R), Gross Motor Function Measure-88 (GMFM-88) and Functional Independence Measure for children (WeeFIM) were used as outcome measures to assess therapeutic efficacy. Results: 9 months after first transplantation, symptomatic improvements such as reduced spasticity, ability to crawl with reciprocal pattern, independent walking with walker, independent transfer from bed to floor, improved biting and chewing and cognition were observed. On GMFCS-E&R she improved from level III to level II, GMFM-88 improved from 36.36% to 38.62% and WeeFIM improved from 34 to 38. These improvements were well supported by positron emission tomography–computed tomography which showed improved metabolism in bilateral cerebellum and medial temporal cortex. All these improvements were maintained even at 5 months’ follow up post second transplantation. No adverse events were reported after the procedures or at follow ups. Conclusion: Intrathecal administration of autologous bone marrow mononuclear cells are safe and an effective therapeutic strategy in the management of CP.