University of Pittsburgh researchers have identified a potential treatment for PACS1 and PACS2 Syndromes, severe neurodevelopmental diseases caused by mutations in the PACS1 (Arg203Trp) and PACS2 (Glu209Lys) genes. The research reveals altered interactions between the PACS1 and PACS2 disease variants and the histone deacetylase HDAC6. Experiments using patient-derived fibroblasts show that inhibiting HDAC6 with tubacin can reverse cellular defects associated with these syndromes. This discovery highlights the therapeutic potential of HDAC6 inhibitors for treating PACS1 and PACS2 Syndromes, which currently have no available therapies.
Description
Mutations in the PACS1 and PACS2 genes lead to severe neurodevelopmental disorders characterized by cognitive impairment, speech delay, and motor deficits. The researchers have shown that these mutations alter the binding of PACS1 and PACS2 to HDAC6, resulting in abnormal cellular phenotypes, such as an extended Golgi compartment in patient-derived fibroblasts. By using HDAC6 inhibitors, such as tubacin, the researchers were able to reverse the Golgi defect which is one of the main abnormities for PACS1 and PACS2 syndromes. This discovery opens the door to the development of targeted therapies aimed at correcting the molecular dysfunction caused by PACS1 and PACS2 mutations.
Applications
- Therapeutic Development
- Neurodevelopmental Research
- Personalized Medicine
Advantages
This invention fills a critical gap as no therapies currently exist for PACS1 and PACS2 Syndromes. It offers a novel approach by using HDAC6 inhibitors to target the disease’s molecular mechanisms. Preclinical studies show that HDAC6 inhibition reverses key cellular defects, providing strong potential for developing targeted treatments for these neurodevelopmental disorders.
Invention Readiness
This invention is in the preclinical stage, with in vitro experiments using patient-derived fibroblasts demonstrating that treatment with the HDAC6 inhibitor tubacin can reverse cellular defects associated with PACS1 and PACS2 Syndromes. These findings provide a strong foundation for further drug development and testing, potentially leading to a new treatment option for neurodevelopmental disorders caused by PACS mutations.
IP Status
https://patents.google.com/patent/US20210290612A1
