PPP2R5D STUDY DETAILS & IMPACTS

This research has the potential to touch millions of lives. Here's how.

READ: PPP2R5D Study Prospectus

READ: PPP2R5D Study Summary

WATCH: Dr. Wendy Chung On PPP2R5D

UNDERSTANDING THE PROBLEM

Recent research studies have identified several variances (mutations) occurring in the gene PPP2R5D that are related to or causing a host of neurodevelopmental disorders in the human brain. These disorders include Intellectual Disability (ID), some forms of Autism Spectrum Disorder and associated physical conditions. In addition, the identified mutations are also linked to Alzheimer’s Disease and certain forms of cancer.

FREQUENTLY ASKED QUESTIONS

PPP2R5D is a gene that is involved with cellular growth and development throughout the human body, but especially brain and neurodevelopment. Intellectual disability and autism are common development disorders affecting more than 1% of the general population.
Recently, more than 40 children from around the world have been diagnosed with a rare variation in the PPP2R5D gene that is linked to Intellectual Disability and Autism. These diagnoses came to light from a particular case of Ms. Jordan Lang, an 11-year-old girl in Sacramento, CA, whose diagnosis led to an international study of 6 other children diagnosed in the world. Since that study, the number of known diagnoses has increased to more than 40 children.
According to medical research studies, mutations in the gene PPP2R5D result in significant intellectual disability within children, including, very low IQ (<50), inability to speak, hypotonia (low muscle tone), delayed intellectual development and other significant impacts, such as autism.
Jordan’s Guardian Angels, a non-profit charity established four years ago to assist other children is now pursuing research aimed at finding a way to reverse the mutation for the 40-plus children as well as other undiagnosed children. It is estimated that as many as 250,000 to 300,000 children suffer from this mutation but are currently undiagnosed.
This major research effort is underway, utilizing a team of the best and brightest experts from throughout the U.S. and the world, led by Dr. Wendy Chung from Columbia University Medical School. Jordan’s Guardian Angels is currently pursuing major fundraising efforts to support the conduct of this research.
The funding will be used to conduct the actual research effort, which will include the development of brain cell lines from each of the more than 40 diagnosed children, as well as the creation of mouse models having the same mutation as the children. Once those samples are created the research team will utilize “high throughput drug screening” as well as 3-D modeling of the protein causing the mutation to identify either existing drugs or create new drugs that will treat the condition, as well as provide important medical science clues involving the other conditions mentioned above.

It is believed the research could provide help to a significant portion of the world’s Autism cases. There are also potentially significant gains to be found those suffering from Alzheimer’s Disease (AD) and cancer. Specifically, the protein phosphatase 2A (PP2A) which is involved in mutations on PPP2R5D, is known to contribute to a condition resulting in Alzheimer’s Disease. Our research will provide more understanding of the role of PP2A in the brain and could lead to therapeutic targets for treating AD.

In addition, PP2A is also believed to be a tumor suppressor, and changes in PP2A are also believed to be important to cancer. Our research will provide more information on those connections and may provide more targets for specific drug interventions for cancer.

Jordan’s Guardian Angels has a preliminary budget of approximately $1,500,000 for the first year of research and a total budget of $12,000,000 for a three-year timeline. Our goal is to be conducting human clinical trials in three years.
We initially estimate it will take approximately 6-10 years to complete the studies outlined. It will take approximately $10 million and three to five years to identify a compound that could be tested in human clinical trials. Once a lead compound is identified, we would partner with a pharmaceutical company to begin formal clinical trials and it generally takes at least five years between the time a compound is used first in humans until it is FDA approved.

RESEARCH PROPOSAL & GOALS

Currently, we have identified more than 40 children who are affected by the various mutations of PPP2R5D. As Whole Exome Sequencing (WES) becomes more available as a diagnostic tool we expect that our sample size for the research will increase significantly, with a goal of 100 patients ultimately involved in the research study efforts
The research plan includes the creation of Pluripotential brain stem cells through the collection of cell and blood samples from the identified patients. These cell samples will allow for a detailed observation of the mutations and their characteristics.
The research plan also includes creation of mouse models that have the corresponding genetic mutations. This will allow direct examination of the mouse brain and performance of invasive studies that are not possible in human patients.
High throughput drug screening will be performed to determine those drugs that are effective at either treating or reversing the mutations and testing for toxicity of the drugs on the samples.
The 3D model helps explain the effect of the different mutations on the individuals and enables the development of a targeted drug.
Although we are studying these mutations specifically for their impact on Intellectual Disability as well as Autism Spectrum Disorder, there are other possible byproducts that may be derived from this research. As mentioned above, those include potential impacts on the study of Alzheimer’s Disease as well as cancer.