Fine-tuning Disrupted Brain Circuitry With Focal Gene Therapy
Collaborative research between DCAPBS developmental neurobiologist and psychiatrist Stewart Anderson and pediatric neurology brain circuitry of epilepsy researcher Doug Coulter: Fine-tuning Disrupted Brain Circuitry With Focal Gene Therapy. Drs. Anderson and Coulter have been studying an experimental model of the 22q11.2 deletion syndrome, a relatively common genetic mutation associated with intellectual disability, attentional and learning challenges, and a highly increased risk of schizophrenia. The animals experience similar cognitive disruptions, including weakness in both social and spatial memory. Recordings from brain slices discovered that these disruptions were associated with elevated but "noisier" activity in a part of the forebrain called the hippocampus. The team then used an adeno-associated virus, an approach currently approved for gene therapy in humans for example in blindness, to focally introduce an artifical receptor that is expressed in those same brain cells that were hyperactive. Exposure of the animals to a "designer drug" that only activates the artificial receptor results in an reduced excitatory activity by those previously hyperactive cells. This reduction could be fine-tuned by varying the amount of the designer drug provided. Remarkably, the team was able to find a dose range that successfully normalized the spatial memory problems in adult 22q11.2 deletion in animals. Correcting symptom-related behavioral abnormalities by focal, and tunable, gene therapy targeting specific brain circuits has tremendous promise for future studies aimed at both prevention and treatment of medication-resistant pediatric neuopsychiatric disorders.This work has recently been published in the journal of Biological Psychiatry and was recently chosen for a Cornerstone article.
Foerderer Grant Awardee Alix Timko, PhD
Anorexia nervosa (AN) is a severe psychiatric illness associated with low body weight. The first step in treatment is weight restoration via nutritional rehabilitation and reestablishment of healthy eating patterns. For adolescents with AN "healthy" eating refers to meeting their bodies' nutritional needs, including adequate caloric consumption to feed the body, facilitate weight gain, and ensure consumption of a variety of macro-and micronutrients. In addition, feared or avoided foods need to be reintroduced into the diet. In Family-Based Treatment, the gold standard in treating pediatric and adolescent AN, parents are in charge of the refeeding process. They ensure their child consumes enough food to build back muscle and fat stores and facilitate weight gain at a rate of 2-5 pounds per week. Parents report struggling with shifting their perspective on shopping and food preparation habits from what is often perceived as "healthy" to including typically avoided foods (e.g. high fat foods, "junk foods", calorically dense foods) into their child's renourishment diet. Facilitating a rapid shift in parents' meal planning and food shopping habits could provide them with more support in early phases of treatment-ultimately leading to a more rapid rate of weight gain and improved outcomes in adolescents with AN. We hypothesize that augmenting nutritional education with an internet-based food shopping program that provides real time feedback will increase parent's ability to implement high calorie meal plans at home.
In this project we will pilot the adaptation of an Open Science Online Grocery (OSOG) to shape parental shopping habits. OSOG is a free and open-coded tool developed to test choice architecture within an online grocery retail setting. Researchers are able to assess whether or not food items are placed in or removed from the cart, if nutritional labels are viewed, time spent shopping, and the macronutrient and caloric content of food purchased. From the participants' point of view, OSOG looks like any other online grocery store. From the researchers' point of view, OSOG facilitates easy changes to choice architecture within the store. Researchers can provide participants feedback on the healthfulness of their cart. It is the latter function that has the most potential in supporting parents of adolescents with AN in making changes to how they purchase food. We will work with Parent Research Partners to determine what modifications need to be made to an existing OSOG in order to support choosing high calorie and calorically dense foods. We will then pilot the modified OSOG with 12 parents of adolescents with AN hospitalized for medical stabilization and compare their weight gain in the first four weeks of treatment to the average weight gain of adolescents in our program. If found helpful, we can integrate the OSOG into our nutritional training and/or create educational/training programs using the OSOG.
Congratulations on your Foerderer Grant Alix!