PPP2R5D is a gene involved with cellular growth and development throughout the human body, especially the brain and neurodevelopment. Mutations in this gene have recently been described as a cause of neurodevelopmental disorders that has symptoms including autism, intellectual disabilities, behavioral challenges and seizures. PPP2R5D may also play a role in Alzheimer’s disease and certain forms of cancer.
The identification of these mutations and their impacts presents an opportunity to conduct foundational research aimed at developing therapeutic treatments or possibly reversing the impacts of the mutations.
“Jordan was one of the first children to be diagnosed with the PPP2R5D mutation,” Dr. Honkanen said. “After the diagnosis, no one could explain the disorder because only a few people in the world even knew what PPP2R5D is and none of us were aware of the genetic link.”
In search of answers, Jordan’s father started Jordan’s Guardian Angels. The nonprofit organization heavily relied on the expertise of Dr. Wendy Chung, world-renowned medical detective and geneticist at Columbia University Medical School, who often takes the most difficult cases. Together, they assembled a diverse team of leading researchers from across the world in an effort to find the mechanisms behind the mutation and determine if a cure is possible.
Dr. Honkanen said he was offered to take part in the research project because of his extensive knowledge on protein phosphates. “I have been working on protein phosphates for over 25 years and the USA College of Medicine has an international reputation in the field,” he said. “Dr. Wendy Chung wanted to learn more about PPP2R5D, so when she found the mutation in PPP2R5D – a gene encoding phosphate regulator proteins– she called me and others that study phosphatase to learn more about what this protein does.”
The team of researchers, including Dr. Honkanen, is comprised of human geneticists, neurologists, psychologists, biochemists, protein modelers, model organism researchers and cancer biologists. They are now in the beginning stages of their collaborative research.
Currently, there are 41 children known in the world who have been diagnosed with mutations in PPP2R5D and are experiencing significant intellectual disability, autism and other physical symptoms. In August, Jordan’s Guardian Angels brought 25 of the families from around the world to Chantilly, Va., for a family conference. The families donated blood samples, which helped the research team to begin their investigation.
As a basic science collaborator on the team, Dr. Honkanen’s role is to help determine how the mutations alter the activity of the normal protein. “The USA College of Medicine also has expertise in drug development for phosphates, so we will explore the development of an assay that can identify compounds that bind to the variant protein but not the normal protein,” he said.
According to Dr. Honkanen, before the team can begin searching for a cure, they first need to determine exactly what needs to be fixed. The research team’s ultimate goal is to develop new pharmacological interventions, as some neurodevelopmental disorders are reversible.
Although the team is studying the mutations specifically for their impact on intellectual disability and autism spectrum disorder, there are other possible byproducts that may be derived from this research including significant clues or advancements in the knowledge of Alzheimer’s disease and cancer.
Researchers estimate the study will take six to 10 years to complete, costing upwards of $15 to 20 million. Jordan’s Guardian Angels is leading the funding for the large-scale research project. “The foundation promotes the research team as the best of the best in the world,” he said. “That is flattering to me and also helps to place USA’s research on a global stage.”
Founded in 2003, Jordan’s Guardian Angels is a nonprofit organization with the goal of helping to improve and bring joy to the lives of children and families in the Coachella Valley and beyond.
Click here to watch CBS news segment.
Click here to learn more about the project.
