Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community.

BACKGROUND: Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community. METHODS: Australian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment. RESULTS: In total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function. CONCLUSIONS: Hypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.

Neurodevelopmental Therapy for Cerebral Palsy: A Meta-analysis.

BACKGROUND AND OBJECTIVE: Bobath therapy, or neurodevelopmental therapy (NDT) is widely practiced despite evidence other interventions are more effective in cerebral palsy (CP). The objective is to determine the efficacy of NDT in children and infants with CP or high risk of CP. METHODS: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Medline were searched through March 2021. Randomized controlled trials comparing NDT with any or no intervention were included. Meta-analysis was conducted with standardized mean differences calculated. Quality was assessed by using Cochrane Risk of Bias tool-2 and certainty by using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Of 667 records screened, 34 studies (in 35 publications, 1332 participants) met inclusion. Four meta-analyses were conducted assessing motor function. We found no effect between NDT and control (pooled effect size 0.13 [-0.20 to 0.46]), a moderate effect favoring activity-based approaches (0.76 [0.12 to 1.40]) and body function and structures (0.77 [0.19 to 1.35]) over NDT and no effect between higher- and lower-dose NDT (0.32 [-0.11 to 0.75]). A strong recommendation against the use of NDT at any dose was made. Studies were not all Consolidated Standards of Reporting Trials-compliant. NDT versus activity-based comparator had considerable heterogeneity (I2 = 80%) reflecting varied measures. CONCLUSIONS: We found that activity-based and body structure and function interventions are more effective than NDT for improving motor function, NDT is no more effective than control, and higher-dose NDT is not more effective than lower-dose. Deimplementation of NDT in CP is required.

Education can improve clinician confidence in information sharing and willingness to refer to stem cell clinical trials for cerebral palsy.

To progress stem cell therapies for cerebral palsy, clinicians need to openly engage with patients about emerging evidence and be willing to refer to relevant clinical trials, if and when appropriate. To assess whether education can change clinicians' confidence in information sharing and willingness to refer to relevant clinical trials, an online questionnaire was distributed at a scientific conference before and after a professional workshop on cell therapies for cerebral palsy. Of the 42 participants who completed the survey, 26 self-identified as clinicians. Of these, 81% had had patients ask about stem cells, yet in the pre-workshop questionnaire indicated they were not confident answering questions about cell therapies. Clinicians were most commonly asked about stem cell treatments provided by private clinics, stem cell research and current evidence. Post-workshop, knowledge and confidence regarding stem cells, as well as likelihood to refer to clinical trials using therapies with a strong evidence base (eg, umbilical cord blood/placental cells), significantly increased (p<0.001). This study highlights that by offering resources and education, clinician confidence and willingness to refer to cell therapy trials can improve; this may help drive the stem cell research landscape and support patient decision-making.

Neural stem cell treatment for perinatal brain injury: A systematic review and meta-analysis of preclinical studies.

Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury. Controlled interventional studies of NSC therapy using animal models of perinatal brain injury were identified using MEDLINE and Embase. Primary outcomes were brain infarct size, motor, and cognitive function. Data for meta-analysis were synthesized and expressed as standardized mean difference (SMD) with 95% confidence intervals (CI), using a random effects model. We also reported secondary outcomes including NSC survival, migration, differentiation, and effect on neuroinflammation. Eighteen studies met inclusion criteria. NSC administration decreased infarct size (SMD 1.09; CI: 0.44, 1.74, P = .001; I2  = 74%) improved motor function measured via the impaired forelimb preference test (SMD 2.27; CI: 0.85, 3.69, P = .002; I2  = 86%) and the rotarod test (SMD 1.88; CI: 0.09, 3.67, P = .04; I2  = 95%). Additionally, NSCs improved cognitive function measured via the Morris water maze test (SMD of 2.41; CI: 1.16, 3.66, P = .0002; I2  = 81%). Preclinical evidence suggests that NSC therapy is promising for the treatment of perinatal brain injury. We have identified key knowledge gaps, including the lack of large animal studies and uncertainty regarding the necessity of immunosuppression for NSC transplantation in neonates. These knowledge gaps should be addressed before NSC treatment can effectively progress to clinical trial.