Kazuhito Toyooka
This study aims to investigate the efficacy of PEDF peptides as a medication for autism spectrum disorder and ADNP syndrome. See the details in our lab website (https://toyooka-lab.owlstown.net/).
Pigment Epithelium-Derived Factor (PEDF) is localized at chromosome 17p13.3, and deletions or duplications of this chromosome region result in neurodevelopmental disorders, such as Miller-Dieker syndrome and 17p13.3 duplication syndrome, related to ASD. We recently have found that PEDF plays a critical role in neuronal morphogenesis and neural activity in vivo, including neurite formation, spine formation and calcium signaling. Studies have indicated the possibility of PEDF-derived peptide as a potential medication for tumors and retinopathy. However, little is known about PEDF functions in neurodevelopment in the cortex and the effects of the peptides in neurodevelopmental disorders, such as autism.
In addition, we are interested in testing the peptides in the ADNP syndrome, which is caused by a mutation in the ADNP (activity-dependent neuroprotective protein) gene and associated with a variety of symptoms, such as ASD, ADHD and intellectual disability.
Autism spectrum disorder (ASD) is characterized by four core symptoms, which are 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. ASD is a huge burden on not only patients but also their families and local and federal health systems. 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 ASD are essential.
According to our preliminary data on PEDF peptides in autism model mice, the peptides have potential as a medication. The peptides will be tested in other models of mice and systems, and we hope to move forward to testing them in humans in the near future.
Drexel University
In this article, ADNP knockdown in developing cortex leads to multiple abnormalities, including sine formation, neural connectivity and Ca2+ signaling.
