Treatment of Cerebral Palsy with Stem Cells

Cerebral Palsy (CP) is a amalgamate of conditions that results in permanent, non-progressive motor disability. It may be cause due to perinatal hypoxic insults, developmental brain abnormalities, genetic conditions, traumatic or infectious causes. This can happen at any time during gestation resulting in variations in the clinical pattern observed. The consequence is a major burden on the patient and family both socially and financially. It is estimated that 2 per 1000 babies are born each year with CP. Improvements in the neonatal care had little or no effects to date on this incidence. There are several classifications used for CP depending on different elements of the motor functions. The Gross Motor Function Classification System (GMFCS) detailed below is adjusted to age and reflects the degree of independent activities and functions. Another way classify CP is by the number of affected limbs (e.g. quadriparesis, hemiparesis, hemiplegia, etc.). One more method is based on the presence or absence of spasticity, coordination, and muscle tone. Most individuals with CP experience additional neurological comorbidities, related to speech, cognition, behavior, epilepsy and pain that affect them throughout their lifespan. For Example, among people with CP, 75%suffer pain, 50% have intellectual disability, 33% cannot walk, 25% cannot talk, 25% have epilepsy, 25%have incontinence and 10% are blind. Both motor impairment and non-motor comorbidities vary across individuals, emphasizing that outcome metrices need to assess multiple domains. 

Some early warning signs in baby younger than 6 months include, babies head lags when you pick him up while he’s lying on his back, feels stiff, floppy, when you pick him up, his legs get stiff and they cross or scissor. In the baby older than 6 months include, they don’t roll over in either direction, cannot bring both hands together, difficulty in bringing hands to mouth, they reach out with only one hand while keeping the other fisted. In a baby older than 10 months include the symptoms like he crawls in lopsided manner, pushing off with one hand and leg while dragging the opposite hand and leg, cannot stand holding onto support. 

The risk factors include low birthweight and premature birth, multiple birth, infections during pregnancy, blood type incompatibility between mother and child, exposure to toxic substance, mothers with thyroid abnormalities, breech presentation, complicated labor and delivery, small for gestational age, jaundice etc.

Stem cells are multipotent progenitor cells that have been shown to have regenerative as well as immunomodulatory and growth stimulating properties. They have been shown in vitro to have the capacity to induce angiogenesis and differentiate into different types of cells including cells of the nervous system. The primary goals of cell-based therapies is to replenish cells, restores circuitry, normalize the microenvironment, and thus CNS activity, accomplishing this depends on a spectrum of diverse neural cells interacting in concert inn the correct spatiotemporal pattern. The mechanisms by which stem cells might treat cerebral palsy include (a) regenerative mechanisms, replacement and/or repair of damaged brain cells brought about by engraftment and proliferation of transplanted cells, which may include differentiation of transplanted cells into new microglia or astrocytes to promote reorganization, (b) anti-inflammatory mechanisms, attenuation of the inflammatory immune response to brain injury, via reduction in the release of excitotoxins, cytotoxins and oxygen free radicals, (c) trophic mechanisms, to promote cell survival via release of neurotrophic factors secreted from progenitor cells to induce endogenous cell migration, proliferation and differentiation and/or to promote angiogenesis and new blood vessel formation.

The stem cells niche is a special microenvironment that is suitable for stem cells. It mainly depends on adjacent cells, extracellular matrix and various cytokines. The homing effect of stem cells is the entire process of directed migration of the activated stem cells after injection into the target brain tissue along the concentration gradient and performing regenerative functions.

Stem cell intervention is not yet a complete cure but has a larger treatment effect than rehabilitation alone. The rate of serious events reported in clinical trials has been low, suggesting an acceptable benefit:risk ration.