Neuromorphogenesis and Neural Circuit Development: The Pedf/Plxdc1/Adnp Signaling Pathways
Abstract
Topic Area of the Research: This project addresses one of the Fiscal Year 2022 Autism Research Program Idea Development Award Areas of Interest: Assessment of novel therapeutics using valid preclinical models. Our research will assess the efficiency of a novel therapeutic medication using well-established autism mouse models. We will focus on early stages of brain development, where defects can have profound effects on subsequent brain activity and behavior. We believe that correcting defects in early brain development with our proposed medication would prevent autism from developing or reduce symptom severity. This results in the improvement of the patients’ quality of life and their families by reducing symptom severity without the need for lifelong daily medication. In addition, our research will provide insights into the mechanisms underlying the differences seen in autism between men and women by separately analyzing the responses in male and female mice. Central Critical Problems: In April 2021, the Center for Disease Control and Prevention announced that the prevalence of autism spectrum disorder in the United States is 1 in 44 children. More than 5.4 million (more than 2%) of Americans and 7.5 million (about 1% ) of the world population have autism spectrum disorder. Also, it is reported that more than 20,000 military dependents have autism spectrum disorder. Autism spectrum disorder is characterized by four core symptoms: (1) impaired communication and social interaction, (2) restrictive interests, (3) repetitive behaviors, and (4) irritability. Many patients with autism spectrum disorder experience daily pain and frustration, as many cannot make friends, engage in social activities, or find comfort in most environments. Autism spectrum disorder is a huge burden on not only patients but also their families and local and federal health systems. More importantly, this creates huge challenges both for the soldiers with autism spectrum disorder and their family due to the long separation and less access to proper treatments during their active service. There is an urgent need to alleviate these burdens, but to date, no effective treatments addressing the cause of autism spectrum disorder exist. Current medications are limited only to reducing irritability. To relieve the severe burdens of this disease, developing improved and novel medications that can address the other core symptoms of autism spectrum disorder are essential. The creation of a new effective medication will improve patients’ physical and mental health, by increasing their ability to communicate and learn, as well as reduce the strain on families and institutions such as health care and mental and social services. By providing treatment for the children of active Soldiers and Veterans, the strain on their families at home would be reduced. Innovation: The proposed studies are conceptionally innovative as we are the first to validate the possibility of protein-derived peptides, pigment epithelium-derived factor and activity-dependent neuroprotective protein, as potential therapeutic medications to reduce autism spectrum disorder. Studies have indicated the possibility of the peptides derived from pigment epithelium-derived factor as a potential medication for tumors and retinopathy. However, little is known about its functions in brain development and its effects on neurodevelopmental disorders like ASD. In addition, our approach is unique in terms of targeting early developmental stages. Many previous studies have focused on the functions of mature neurons. While this is important, recent studies revealed the importance of early developmental stages, including the brain and neuron formation, that may affect later developmental stages, including neural activity and behavior. The mechanisms behind the flaws in early development in autism spectrum disorder have not been thoroughly investigated, and the potential medications tar
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310190
Entities
People
- Kazuhito Toyo-oka
Organizations
- Drexel University
- United States Army