Welcome to this month's Research Roundup, a recurring overview of recent studies published by researchers at BC Children's Hospital Research Institute (BCCHR) and the University of British Columbia, and their collaborators.

BC Children's Hospital Research Institute Research RoundupMedicinal cannabis could reduce behavioural difficulties in autistic children

BCCHR theme: Brain, Behaviour & Development

Autism is a neurodevelopmental condition diagnosed in one in 66 children in Canada. Some autistic children experience behavioural difficulties such as self-injury and aggression, yet parents report a lack of effective, long-term treatment options. Medicinal cannabis has emerged in recent years as a promising option for helping to improve some autism-related behaviours. Dr. Harold Siden, Sarah Fletcher, Colleen Pawliuk, Dr. Angie Ip, Dr. Linda Huh, Dr. Rod Rassekh and Dr. Tim Oberlander conducted a scoping review of eight studies that looked at the use of medicinal cannabis formulations in autistic children and adolescents. Symptoms commonly reported as improved during treatment included anxiety, behavioural challenges, cognitive deficits, hyperactivity, mood, self-injury and sleep disturbance. Some of the studies reported that participants were able to reduce their other medications (e.g., benzodiazepines) while taking medicinal cannabis; and six of the eight studies reported mild adverse events such as sleepiness, changes in appetite and restlessness.

“These studies were characterized by variations in study designs (observational studies, retrospective reviews and case studies), sample sizes, outcome measures, duration of treatment and nature of side effects. All studies reported improvement in autism-related behavioural symptoms after starting on medicinal cannabis treatment,” wrote Dr. Siden and his team in “Medicinal Cannabis in Children and Adolescents With Autism Spectrum Disorder: A Scoping Review.” The researchers caution that stronger evidence of medicinal cannabis’s efficacy in reducing autism-related symptoms is needed.

Read more in Child: Care, Health and Development.

Using CRISPR to fine-tune new treatment for transplant rejection

BCCHR theme: Childhood Diseases

Transplant rejection occurs when an organ recipient’s immune system attacks the donated organ. Current treatment involves the use of immunosuppressive drugs, but this can leave patients vulnerable to other diseases such as infections or cancer. Dr. Megan Levings, Dr. Avery Lam and Jana Gillies, with assistance from Dr. Michael Kobor, Dr. David Lin and additional collaborators, have developed a new approach to this problem by engineering a type of immune cell known as a regulatory T cell (Treg) to be used as a cell therapy. This treatment strategy works by dampening the immune response to a specific target, like a donated organ, while leaving the immune system fully capable of dealing with other threats. To perfect this type of treatment, the team interrogated the underlying biology of these cells. In a new paper titled “Optimized CRISPR-Mediated Gene Knock-In Reveals FOXP3-Independent Maintenance of Human Treg Identity,” the team optimized a method of generating these Tregs using CRISPR to successfully switch in or out genes of interest. As part of the study, they eliminated FOXP3, a key component of Tregs, and surprisingly found that this had little impact on the overall function of the cells. Neither DNA methylation, mRNA or protein expression were largely affected, suggesting that although FOXP3 is crucial for Treg development, it may not be needed once these cells have matured.

“Our goal is to move forward from unmodified Tregs to a more tailored therapy that is specific to a child’s condition,” said Avery Lam. “The next steps are to use these techniques to investigate other genes to further refine this cellular therapy.”

Read more in Cell Reports.

An adolescent’s gender plays important role in shaping food choices during transition to secondary school

BCCHR theme: Evidence to Innovation

The transition between elementary school and secondary school is typically marked by a decline in eating habits, such as eating less fruits and vegetables, consuming more sugary foods and beverages, and skipping meals. Dr. Louise Mâsse, Alysha Deslippe and their collaborators found that this decline in eating habits is impacted by different societal expectations placed on boys and girls. For example, girls are typically influenced by the pressure to be thin while boys are influenced by the pressure to gain muscle mass. Policy guidelines in Canada have called for more multi-level interventions that focus on the effects of different environments and social influences on dietary behaviours in adolescence. The researchers’ findings, however, highlight the need to consider different gender-specific patterns of behaviour that may complicate one-size-fits-all interventions designed to target this age group. These gender-based differences should help inform the development of future interventions.

“We found that boys’ and girls’ dietary behaviours became increasingly differentiated along gendered lines following the transition [from elementary to secondary school]. … As schools have been suggested as a highly feasible and efficacious environment in promoting healthy eating among adolescents, future programs within schools should consider gender differences in how boys and girls interact with food,” wrote Dr. Mâsse, Alysha Deslippe and their team in “Gender Plays a Role in Adolescents’ Dietary Behaviors as They Transition to Secondary School.”

Read more in Appetite.

Early-life cytomegalovirus infection increases risk of childhood allergies

BCCHR theme: Healthy Starts

Cytomegalovirus (CMV) is a common virus that impacts populations around the world. While CMV infection is often asymptomatic, it can lead to severe disease outcomes and long-term consequences in some individuals — especially those who are immunocompromised. In Canada, CMV prevalence in children aged 1-2 is under 20 per cent, but prevalence increases with age. Roughly 60 per cent of adults in highly developed countries are infected with CMV by 50 years of age. Dr. Soren Gantt, Dr. Stuart Turvey, Dr. Hind Sbihi, Karen Simmons, Darlene Dai, Dr. Brett Finlay and their collaborators found that CMV infection during early life can lead to significant disruption in the balance of intestinal microbiota. Their research is the first of its kind to provide evidence that early-life CMV infection affects the diversity and number of bacteria in the gut. Their findings also provide evidence that elimination of CMV through vaccination is not likely to contribute to the development of allergies.

“Our work indicates that preventing CMV infection would not put children at increased risk of developing atopy [allergic diseases]. Rather, a CMV vaccine, in addition to preventing CMV-associated morbidity and mortality, might reduce the risk of childhood allergic diseases,” wrote Dr. Gantt and his team in “Early-Life Cytomegalovirus Infection Is Associated With Gut Microbiota Perturbations and Increased Risk of Atopy.”

Read more in Pediatric Allergy and Immunology.


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