news – Center for Precision Animal Modeling (C-PAM)

Driving Innovation for Rare Disorders: UAB C-PAM’s Collaboration on DLG4 Research

The University of Alabama at Birmingham (UAB) Center for Precision Animal Modeling (C-PAM) is actively collaborating with the Hope for Harvey Foundation and DLG4 SHINE Foundation to develop a rat animal model for a DLG4 truncation variant. These two foundations focus on advancing research, translational medicine, treatment options, and early detection for DLG4-related disorders. Patients with variants in DLG4 experience a spectrum of symptoms, including severe cognitive disability, inability to speak, seizures, repetitive behaviors typical of children with an Autism Spectrum Disorder, and lack of motor control.

The UAB C-PAM team is generating a haploinsufficient rat model with a DLG4 truncating variant. The Hope for Harvey Foundation seeks to use this DLG4 model to test various gene therapy approaches for patients with the DLG4 mutations. The UAB C-PAM team also used AI tools, including mediKanren and the NCATS Biomedical Translator, to identify potential drug candidates. A curated list was shared with DLG4 SHINE and Hope for Harvey research teams. Trials with the medication guanfacine showed significant benefits in two patients, as highlighted in an interview with Dr. Joni Rutter of NCATS.

For more information about the Hope for Harvey Foundation and their mission, please visit Hope for Harvey.

C-PAM Drug Predictions for CAMSAP1 entering Drug Therapy Trials

Landon's League & UAB CPAM — Landon’s League Foundation and UAB C-PAM

Landon’s League Foundation is dedicated to supporting the development of treatments for rare pediatric genetic diseases and helping those affected by CAMSAP1-related disorder providing adaptive equipment to assist daily living activities. Landon and eight other children worldwide have been identified to share the same unnamed condition caused by inheriting two abnormal copies of the CAMSAP1 gene. This condition/disease causes several issues including seizures, microcephaly (small head size), global developmental delay, severe neurodevelopmental delay, and vision impairment.

The University of Alabama at Birmingham (UAB) Center for Precision Animal Modeling (C-PAM) is collaborating with the Landon’s League Foundation research team to generate a mouse model with an early truncation and find therapies that can be repurposed for treatment. While the mouse model is underway, C-PAM researchers shared drug predictions using artificial intelligence (AI) reasoning tools like mediKanren and NCATS Biomedical Translator, that have since been tested through a low-throughput drug screen in an existing CAMSAP-deficient worm model developed by Dr. Jana Marcette at Montana State University Billings. Three of the candidates were found to rescue the convulsion phenotype that was observed in the CAMSAP-mutant worms. As the Landon’s League research team continues its investigation into drug repurposing candidates, UAB C-PAM is working to generate a mouse model to further this research.

To read the full article and learn more about Landon’s League’s drug therapy trial breakthroughs, visit Landon’s League news.