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Early Research Milestone Reached; What are iPSCs?

We’ve arrived at a key early milestone in our research into Jordan’s Syndrome, a recently-discovered genetic mutation in the gene PPP2R5D thought to be linked to autism, Alzheimer’s, intellectual disability and cancer.

The first batch of iPSCs (induced pluripotent stem cells) have been created by the New York Stem Cell Foundation (NYSCF), and distributed to Rutgers University for duplication and distribution. The iPSCs were created from blood samples given by our children at the first family conference in Washington, D.C., and will play a critical role in understanding Jordan’s Syndrome – and how it may be reversed, treated or cured.

But – how exactly will that happen? And why are iPSCs so important? We asked our friends at the NYSCF to help explain.

How were the iPSCs created?

NYSCF: Scientists create induced pluripotent stem cells, or iPSCs, by taking a small amount of blood or skin from a patient, and converting these blood or skin cells into a pluripotent state using genetic signals called reprogramming factors. These pluripotent cells are able to multiply indefinitely and also can be coaxed into turning into any type of cell in the body, making them a unique and powerful research tool.

iPSCs enable scientists to study the cells affected by disease in the lab without harming patients. For example, the iPSC lines we are making in collaboration with Jordan's Guardian Angels will allow researchers to study patient-derived brain cells without brain surgery.

Because Jordan’s Syndrome is a rare disease with only a few dozen known patients worldwide, the stem cell lines we are making will provide a foundational resource for researchers who may not have easy access to patients. These patient-specific iPSC lines will be an invaluable tool for Jordan's Syndrome researchers around the world.

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How many were created?

NYSCF: So far, NYSCF scientists have created five iPSC lines using blood samples from five different Jordan’s Syndrome patients. Each of these patients has a unique mutation in the gene implicated in the disease, PPP2R5D. Since the disease is so rare, these 5 lines represent a diverse segment of patients.

In addition to creating iPSC lines from additional patients, we are also planning to use stem cells to study the genetics of Jordan's syndrome. Using cutting-edge gene editing technology, our scientists will introduce PPP2R5D mutations into stem cells from a healthy individual. This 'manufactured disease line' will allow scientists to study the specific effects of disease-causing mutations, without being confounded by other differences between patients and healthy people that may be unrelated to the disease.

How can stem cells be used to find potential breakthrough treatments for Jordan’s Syndrome, and potentially related medical mysteries?

NYSCF: Stem cell technology allows scientists to create the different cell types affected in Jordan's Syndrome as patient-specific models of the disease. Modeling Jordan’s Syndrome in a dish using stem cell technology enables scientists to study how the disease develops in different cell types and affects their behavior over time. For example, scientists can derive patient neurons from stem cells, and even combine different types of patient brain cells into 'mini-brains' known as organoids, to study how brain function and the interactions between different cells are affected in Jordan's Syndrome. By enabling a better understanding of the disease and clarifying the cellular and molecular defects driven by the genetic PPP2R5D mutations, stem cell technology may point to treatments that can fix these defects and therefore alleviate disease symptoms.

Stem cell technology also allows new drugs to be directly tested on affected cells or organoids, to see if they have a beneficial effect. This "clinical trial in a dish" approach can help to identify new treatments that may be helpful for certain patients and ineffective – or even potentially toxic – to others.

The cellular processes that go awry in Jordan's Syndrome may well be playing a role in several other diseases – for example, the gene implicated in Jordan’s syndrome is also associated with autism, Alzheimer’s disease, and cancer. Stem cell technology has already advanced research into neurological diseases and cancer, just as we expect it will in Jordan's syndrome. A better understanding of what goes wrong in Jordan's Syndrome will help us understand how the processes in human development are supposed to work, and offer insights into other ways they go wrong in related diseases. There are mounting examples of rare disease research that have taught us something new about common diseases and how to treat them. So a new way to study the dozens of patients with Jordan's Syndrome could end up advancing knowledge and treatments for diseases that affect millions.

Give some perspective on how revolutionary this kind of science is, and its promise for medicine.

NYSCF: Stem cell research is a very young field. Embryonic stem cells were only first isolated in 1998, and the field drastically changed in 2006 with the development of induced pluripotent stem cells by Dr. Shinya Yamanaka, who received the Nobel Prize for this work just six years later. iPSCs made it possible to derive patient-specific cells, fueling the "disease-in-a-dish" and "clinical trial in a dish" research that has never been possible.

So the field has only really been in existence for just over a decade. It is truly the cutting edge of scientific inquiry with new discoveries, tools, and technology published every day. It is such an exciting time to be a stem cell researcher – as well as a disease researcher, because of the opportunities afforded by stem cell technology.

The promise of stem cell research is vast. At some point in our lives, we or the people we love become patients. Traditionally, much disease research and drug discovery have been performed using mouse models. But we are not mice, and to treat diseases more effectively we need to understand how diseases and drugs affect human cells – especially the types of cells involved in the disease. Taking brain cells out of patients to study them in the lab is not usually an option, but stem cell technology makes this type of research possible. The opportunity to create patient-specific stem cell lines has been revolutionary, because each patient is different, in what causes their disease, the way the disease manifests, and how they will respond to drugs. Stem cell research will therefore allow us to understand and treat disease in a more precise and personalized way than ever before possible.

Ultimately, our mission at NYSCF – and the goal in all of our collaborative stem cell projects – is to accelerate research towards cures for all devastating diseases, including Jordan’s Syndrome.

Published

July 30, 2018

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Research Update: Team Meets in Denver, Reports Progress

The Jordan’s Guardian Angels research team converged in Denver, Colorado last weekend to collectively discuss the progress made in our quest to reverse, treat or cure Jordan’s Syndrome, a recently-identified mutation in the gene PPP2R5D.

The meeting came shortly after the State of California allocated nearly $12 million in this year’s state budget to help fund our research. Jordan’s Guardian Angels is partnering with the UC Davis Institute for Regenerative Cures to facilitate the distribution of the funding. The Institute is also providing important support in multiple research functions, joining our international team of scientists and geneticists.

“Researchers are working together in a way that I’ve never seen researchers work together and pull together,” said JGA lead medical investigator Dr. Wendy Chung. “We have the best and the brightest in the world being able to think together, and the energy you can feel coming out of this is just exhilarating.”

Substantial milestones have been reached since the last time the research team met in December in New York City. The first collection of induced pluripotent stem cells (iPSCs), created from blood samples given by children impacted by Jordan’s Syndrome, were produced and distributed by the New York Stem Cell Foundation and Rutgers University.

“The iPSCs are useful to study how the PPP2R5D variants affect cell behavior,” said JGA researcher Dr. Richard Honkanen. “These studies will help us understand what is different in the variant cells versus normal cells. Finding out what is wrong represents the first step in the development of a potential cure.”

Several mouse models have also been created, so researchers can further study the impacts and causes of Jordan’s Syndrome. Our medical team also provided detailed updates regarding newly-produced clinical data, shedding further light on the genetic mutation and its specific variants. More than 60 people have now been diagnosed with Jordan’s Syndrome worldwide, though it’s believed there could be hundreds of thousands of undiagnosed cases.

“The amount of work that’s been done in the first year is pretty amazing,” said Jordan’s Guardian Angels co-founder Joe Lang. “10 years ago, it would’ve taken 10 years to get that first year’s work done. That’s how fast it’s moving.”

In the days and weeks following the Denver workshop, our researchers will develop a plan plotting a broad course of the study over the next three years. Momentum continues to build toward reaching our goal of treating or reversing Jordan’s Syndrome. The genetic mutation is also believed to be linked to – and may bring breakthroughs for – autism, Alzheimer’s and cancer.

Published

July 23, 2018

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Francis 2

Our Global Community: Students Go Above & Beyond

In today’s edition of “Our Global Community,” we’re celebrating the incredible, life-changing bond between 9-year-old Francis Grant, one of the 60-plus children in the world diagnosed with Jordan’s Syndrome, and his fellow classmates.

Francis has attended Letterkenny Educate Together in Donegal, Ireland, for three years. The elementary school fosters an open, inclusive atmosphere for students to learn and grow together. But it wasn’t an easy choice to send him to school.

“Taking Francis into school was one of the hardest decisions to make for me,” said Francis’ mom Gina in a post to the school’s Facebook page. “I had him at home with 24/7. The thought of him being with strangers – and because he has no communication – I was heartbroken thinking he wouldn’t be able to tell me he was scared or lonely.”

What happened next is a testament to the power of inclusiveness. Francis’ classmates didn’t turn away. They welcomed him with open arms into the school’s community. Their unwavering support has helped Francis grow in leaps and bounds.

"He has changed so much in his 3 years there,” Gina said. “He is accepting social situations with ease now. This would never have happened before. He is far more aware and for the first time this past two months, giving hugs. He enjoys being with the other students so much, who play with him and read to him daily. He tries to feed himself and do what they do. It’s great to watch. He is looking at books and interacting with people and toys, which he never did before starting school."

Recently, Francis’ classmates won a contest, and instead of keeping the prize money, they gave it to his teacher to pay for extra resources for him. They also made Francis a sensory mat, a key developmental tool.

“These students and this school has helped us all see the boy behind the silence,” Gina said. “I’ll always be grateful they accepted him and his family with open arms, and they have shown to us that inclusion can – and does – work.”

Published

July 3, 2018

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Jordan’s Guardian Angels is a public charity exempt from Federal Income Tax as an organization described in Section 501 (c)(3) of the Internal Revenue Code, EIN 90-1022228. Contributions to Jordan’s Guardian Angels are tax deductible to the fullest extent allowed by law. No goods or services were provided in consideration for the contributions except as reported above.