Scientific Team

wendy

Dr. Wendy Chung, MD, PhD

Columbia University

Overall Study Principal Investigator
Professional Photo_Mirzaa_2018-min

Dr. Ghayda Mirzaa, MD

Seattle Children's Hospital

Clinical and Molecular Spectrum of PP2A Related Disorders
Janssens

Dr. Veerle Janssens, PhD

KU, Leuven

Signaling functions of PP2A in cancer cells, in neuronal processes and neurologic diseases
Honkanen

Dr. Richard Honkanen, PhD

University of South Alabama

Ser/Thr phosphatase inhibitors and high throughput screens
Strack,Stefan

Dr. Stefan Strack, PhD

University of Iowa

Protein phosphatase 2A in neuronal signal transduction
Xing

Dr. Yongna Xing, PhD

University of Wisconsin-Madison

PP2A structural biologist
Wadzinski

Dr. Brian Wadzinski, PhD

Vanderbilt University

PP2A cell biology in Drosophila
xia

Dr. Houhui (Hugh) Xia, PhD

University of Rochester

PP1 in the nervous system; mouse models with altered PPase activity in the brain; electrophysiology and behavior
Kyle Fink

Dr. Kyle Fink, PhD

UC Davis Neurology and
Institute of Regenerative Cures

Stem Cell Program
Jan Nolta

Dr. Jan Nolta, PhD

UC Davis Institute
for Regenerative Cures

Stem Cell Program
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An International Dream Team

PPP2R5D Researchers

Top researchers from around the globe are assembling to examine the link between known PPP2R5D, PPP2R5C, and PPP2R1A gene variations identified in children and neurodevelopmental disorders including autism, intellectual disabilities, behavioral challenges and seizures.

The international team of human geneticists, neurologists, psychologists, biochemists, protein modelers, model organism researchers and cancer biologists aim to study the mechanism of the gene variation to gain a deeper understanding and develop possible treatments for the future.

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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 RESEARCH

Recent research studies have identified several variances (mutations) occurring in the genes PPP2R5D, PPP2R5C, and PPP2R1A 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, epilepsy, Parkinson'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.
More than 175 children from around the world have been diagnosed with a rare variation in the PPP2R5D, PPP2R5C, and PPP2R1A genes that is linked to Intellectual Disability and Autism. These diagnoses came to light from a particular case of Ms. Jordan Lang, a teenage 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 175 children.
According to medical research studies, mutations in the genes PPP2R5D, PPP2R5C, and PPP2R1A result in significant intellectual disability within children, including 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 more than 175 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 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 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.

We initially estimate it will take approximately 6-10 years to complete the studies outlined. It will take approximately 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 175 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.
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.

ADDITIONAL VARIANTS

Recently, our research team has identified variants on two additional genes. It is believed these variants are connected to the PPP2R5D study. We have now incorporated the variants on these genes, PPP2R51A and PPP2R5C, into our research. The symptoms and impacts appear similar to those caused by the mutation on the gene PPP2R5D which causes Jordan's Syndrome. We are welcoming families with loved ones impacted by these additional gene variations into our global community.

LEARN FROM THE EXPERTS

The research team goes in-depth to
explain what's known about PPP2R5D.

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RECENTLY PUBLISHED RESEARCH

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ADDITIONAL RESOURCES

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