The future of Fragile X research depends on inspiring and encouraging new generations of researchers to push Fragile X forward. That’s why we offer the annual Summer Student Fellowship, which assists young researchers in their pursuit to study Fragile X.
Today, we’re proud to announce the four summaries of this year’s award recipients.
A Controlled Trial of Sertraline in Young Children with Fragile X Syndrome
Salpi Siyahian
University of California, Davis
Mentor: Dr. Randi Hagerman
I had the honor of working at the UC Davis MIND Institute as a research study coordinator under the mentorship of Dr. Randi Hagerman. The study I helped coordinate looked at the benefits of a low dose of sertraline, an SSRI that increases the level of serotonin, on language, anxiety, and social deficits in young children with Fragile X syndrome (FXS).
A preliminary analysis of the first 30 subjects showed improvements in cognition, language, and social behavior through significant improvements in the CGI-I, VAS, and Mullen assessments. Working on this project has reinforced my interest in targeted treatments in FXS and I am excited to see the positive impact of this study on the younger FXS population.
This study will continue to enroll children with FXS between the ages of 24-68 months until mid-January 2015.
Excitatory/Inhibitory Modulation and the Fragile X Synapse’
Matthew Davenport
Cincinnati Children’s Hospital Medical Center
Mentor: Dr. Craig A. Erickson
I worked with Drs. Craig Erickson and Tori Schaefer to assess the efficacy of two GABA(A) modulators, which boost inhibitory signaling in the FMR1 knock-out mouse model of FXS. Deficiencies in inhibitory signaling, dendritic spine number and spine morphology are suspected to contribute to the pathophysiology of FXS in both patients with FXS and in mouse models.
My work included the chronic treatment of FNR1 knock-out mice, collection and processing of brain tissue, microscopy and quantification of dendritic spine density and characterization of spine morphology.
Preliminary data indicate a differential effect of the therapeutics on the FXS dendritic spine phenotype, likely related to the different specificity of the drugs to regulate inhibitory signaling. Further studies evaluating the effects of these drugs on neural physiology and behavior are currently ongoing.
Improving Health Education for Women Who Carry an FMR1 Premutation
Whitney Espinel
Emory University School of Medicine
Mentor: Dr. Stephanie Sherman
Much of the current research on the FX premutation is focused on defining health risks (e.g. FXPOI/FXTAS) and less is dedicated to understanding the personal experiences of women seeking to understand and navigate their own health journey.
My project used focus group discussions to uncover both barriers and facilitators faced by women who carry the premutation when seeking medical care. We uncovered many barriers to personal healthcare including the lack of knowledge among medical providers, inability to keep pace with findings from research in the field, and the shortage of premutation-specific educational materials and support.
The second half of this project aims to create and distribute premutation-specific educational materials for women. Many premutation carriers face the task of educating not only themselves but also healthcare providers and family members. Having access to up-to-date materials can help diminish misperceptions regarding health risks and aid in information sharing and awareness.
Genetic Markers Predictive of Sertraline Treatment Response in Young Children with Fragile X Syndrome
Stefan Sweha
Department of Biochemistry and Molecular Medicine, University of California, Davis
Mentor: Dr. Flora Tassone
Young children with FXS can present with anxiety, irritability, and hyperactivity related to sensory hyperarousal and language delay. Recently, Winarni et al. (2012) reported that treatment with Sertraline led to improvement in expressive language capability in boys with FXS. A positive response to sertraline was recently observed (Winarni et al., 2010) in young children with FXS and autism spectrum disorders. In addition, a preliminary analysis of children in a double-blind, placebo-controlled trial of sertraline in young children with FXS showed a marked improvement in anxiety.
In this study we determined if the genetic allelic variants of several genes related to the serotonergic pathway correlate with the observed clinical response. Data analysis is currently in progress.
Winarni TI, Chonchaiya W, Adams E, Au J, Mu Y, Rivera SM, Nguyen DV, Hagerman RJ. (2012) Sertraline may improve language developmental trajectory in young children with Fragile X syndrome: a retrospective chart review. Autism ResTreat. 104317. doi: 10.1155/2012/104317.