Stem Cell Therapy for Cerebral Palsy

What is Cerebral Palsy? 

Cerebral palsy (CP) is a group of disorders that affect movement and muscle tone or posture. It’s caused by damage that occurs to the immature, developing brain, most often before birth. 

It is one of the leading causes of childhood disability and affects the individual’s development and ability to function. CP encompasses a group of movement disorders and affects posture. Motor limitations are attributed to a static disturbance in the developing brain, often accompanied by associated impairments and secondary health conditions. 

What Causes Cerebral Palsy?

The pathogenesis of CP is still unclear, and several factors are considered to contribute to CP, such as prenatal factors (hypoxia and infections), birth weight as well as genetic factors. Despite new developments in the field of obstetrics and perinatology, incidence of CP is reported as 2 out of 1,000 live births in premature deliveries and 1.1 out of 1,000 live births in mature babies. 

Many factors can lead to problems with brain development, some know problems are: 

• Genetic mutations that result in genetic disorders or differences in brain development. 
• Lack of oxygen to the brain related to difficult labor or delivery.
• Maternal infections that affect the developing fetus.
• Bleeding into the brain in the womb or as a newborn.
• Infant infections that cause inflammation in or around the brain. 
• Traumatic head injury.

What are Common Signs and Symptoms? 

Signs and symptoms appear during infancy or preschool years. In general, cerebral palsy causes impaired movement associated with exaggerated reflexes, floppiness or spasticity of the limbs and trunk, unusual posture, involuntary movements, unsteady walking, or some combination of these. 

People with cerebral palsy can have different problems, such as swallowing problems and commonly have eye muscle imbalance, in which eyes don’t focus on the same object. The also might have reduced range of motion at various joints of their bodies due to muscle stiffness. The signs and symptoms can be divided in 4 groups: 

Movement and Coordination

• Stiff muscles and exaggerated reflexes (spasticity). 
• Lack of balance and muscle coordination (ataxia). 
• Tremors or jerky involuntary movements.
• Favoring one side of the body. 
• Difficulty walking.
• Difficulty with fine motor skills. 

Speech and eating

• Delays in speech development.
• Difficulty speaking.
• Difficulty with sucking, chewing or eating.
• Excessive drooling. 

Development

• Delayed development in reaching motor skills, such as sitting up or crawling.
• Learning difficulties.
• Intellectual disability.
• Delayed growth. 

Others

• Seizures (epilepsy). 
• Hearing difficulties. 
• Vision problems and abnormal eye movements. 

Current Treatment Options

Patients with this condition may require lifelong care with a medical care team. 

There is no cure for cerebral palsy. However, there are treatment options that may help improve the child’s daily functioning and early interventions can improve outcomes. 

Some medications used to lessen muscle tightness might be used to improve functional abilities, treat pain and manage complications that are caused by spasticity or other symptoms. These include muscle or nerve injections with botox or other agents and oral muscle relaxants.

All patients should have a program of physical therapy, occupational therapy and speech and language therapy. 

Recently, the use of mesenchymal stem cells (MSCs) infusion has been considered as a promising therapeutic alternative in clinical practices and numerous trials have been conducted. 

Stem Cell Therapy 

Stem cells are characterized as cells with the capacity of self-renewal and differentiation into multiple tissues. They are a heterogeneous population of multipotent cells that can differentiate into bone (osteoblasts), fat (adipocytes), cartilage (chondroblasts) and periosteum (fibroblasts). 

Umbilical cord and bone marrow stem cells are a rich source of stem cells. It is more convenient to obtain human umbilical cord stem cells due to their low immunogenicity when compared to other types of MSCs. 

Combined therapies have become a common strategy for CP treatment, in which stem cell therapy is combined with rehabilitation training as an adjunctive therapy. 

Clinical Trials with Umbilical Cord-derived MSCs

A study published in the journal Stem Cells International evaluated the use of Wharthon’s jelly MSCs (WJ-MSCs) in children with cerebral palsy during a medical therapeutic experiment. A total of 54 patients were included and each one received 1-10 infusions and was examined by a neurologist. 

A 6-point Likert scale was used to assess the quality of life and self-sufficiency of the patients on the basis of the neurological examination. Children with >50% follow ups were included into the analysis. 48 of 54 patients (88.9%) achieved some improvement in health status, including increase in the quality of life and 21 patients (38.9%) achieved an increase in their self-sufficiency level. 

Another study published in the journal Cell Transplantation evaluated the use of Umbilical cord blood MSCs (hUCB-MSCs) infusion. The study included 54 patients that received basic rehabilitation as a background treatment. They were divided into 2 groups, the first group were the one that received 4 infusions of hUCB-MSCs (at a dose of 5 Million cells) and basic rehabilitation treatment (27 patients); and a control group which received rehabilitation and 0.9% normal saline (27 patients).

Several indices were tested from baseline and up to 24 months after the infusions, including the gross motor function measurement 88 scores, comprehensive function assessment, lab tests, electroencephalogram (EEG), MRI and adverse events. 

Functional improvement scores were significant in the infusion group at 3, 6, 12 and 24 months post-treatment. Also, significant improvement in gross movement was shown after hUCB-MSCs infusion. 

Serious adverse events were not observed during the whole study period. The results of the study indicated that hUCB-MSC infusion with basic rehabilitation was safe and effective in improving gross motor and comprehensive functions in children with CP.

Although there are not many clinical studies, several ongoing studies and small clinical studies have shown promising results with the use of stem cell therapy for a condition that lacks treatment options that have a significant improvement in the quality of the patients’ life. 

Sources:

https://www.mayoclinic.org/diseases-conditions/cerebral-palsy/symptoms-causes/syc-20353999

Eggenberger S, Boucard C, Schoeberlein A, et al. Stem cell treatment and cerebral palsy: Systemic review and meta-analysis. World J Stem Cells. 2019;11(10):891-903. doi:10.4252/wjsc.v11.i10.891.

Boruczkowski D, Zdolińska-Malinowska I. Wharton’s Jelly Mesenchymal Stem Cell Administration Improves Quality of Life and Self-Sufficiency in Children with Cerebral Palsy: Results from a Retrospective Study. Stem Cells Int. 2019;2019:7402151. Published 2019 May 2. doi:10.1155/2019/7402151

Huang L, Zhang C, Gu J, et al. A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal Stem Cell Infusion for Children With Cerebral Palsy. Cell Transplant. 2018;27(2):325-334. doi:10.1177/0963689717729379.

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