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Finding a cure for Schimke Immuno Osseus Dysplasia (SIOD)


We help to accelerate the development and delivery of new therapies and treatments,  and facilitate a place of hope for SIOD families and their children with information and resources to help them navigate life with this disease.

Our lab does alot of work in conjunction with other doctors and labs. We are excited about the collaboration with Dr. Matthew Porteus, who is considered one of the pioneers and founders of the field of genome editing—a field that now encompasses thousands of labs and several new companies throughout the world.
November 2023 Update from Stanford

Your funding has allowed Dr. Lewis' lab to begin unraveling the mystery of how SMARCAL1 protein deficiency leads to the clinical features of SIOD.

As you know, SIOD is caused by mutations of the SMARCAL1 gene. These mutations disrupt the normal DNA repair function of the SMARCAL1 protein, which somehow leads to cellular dysfunction of the kidney, immune system, growth plates, and blood vessels supplying the brain. While the exact mechanisms by which SMARCAL1 mutations lead to specific clinical features of SIOD are not fully understood, they likely involve the loss of some critical function of SMARCAL1 protein that is necessary to maintain these cell types in a healthy state.

Dr. Lewis aims to illuminate further the relationship between SMARCAL1 and SIOD using induced pluripotent stem cells (iPSCs). iPSCs have revolutionized regenerative medicine and biomedical research due to their remarkable ability to differentiate into various cell types found in the human body.

By reprogramming blood cells from patients, the Lewis Lab is generating iPSCs to create a human cell model that can successfully replicate the disease process that occurs in people who have SIOD. This model enables us to investigate the underlying causes of the disease and test potential treatments.

This advancement represents a huge step forward from previous efforts to create a disease model using genetically modified mice, which were not helpful. Even when mice had mutations in their SMARCAL1 gene similar to those found in SIOD patients, they did not develop any of the major clinical symptoms of SIOD seen in humans.

With the human cell model of SIOD we have today, we are closer than ever to our goal of developing therapies that will treat the range of symptoms caused by the SMARCAL1 mutation, including growth impairment, immune system dysfunction, kidney problems, and abnormal vascular function leading to migraines and seizures.

Your gifts are helping us understand and address migraine and the increased risk of stroke in children with SIOD.


Up to 40 percent of children with SIOD experience a neurovascular symptom called hemiplegic migraine, a rare form of migraine that can cause difficulty speaking, severe headache, and physical weakness on one side of the body. As you well know, sometimes the migraines can even lead to stroke. While it is clear these episodes are caused by a temporary decrease in blood flow to the brain followed by an increase in the diameter of the blood vessels, we do not yet know why they are more common in kids with SIOD—and whether they can be safely and effectively treated using existing migraine medications.

Because blood vessels play a pivotal role in the physiology of migraines, Dr. Lewis is looking at whether there are blood vessel abnormalities in SIOD that may contribute to these clinical problems. He believes there may be abnormalities in the endothelial cells, which form the inner lining of blood vessels. To test this theory, the Lewis Lab is using iPSCs to create endothelial cells and blood vessel-like structures to investigate, for the first time, how the SMARCAL1 protein influences either the differentiation of the blood vessels or their function.

Thanks to blood samples donated by your family, researchers in the Lewis lab already have early evidence that they are pursuing the right path. The total number of endothelial cells created with Paizlee's iPSCs was significantly lower compared to the number created by iPSCs from people without SIOD. This highlights that even in the making of the endothelial cells, the SMARCAL1 protein clearly plays an important role that the researchers had not anticipated.

Within the next six months, the Lewis Lab expects to have a clearer picture of the abnormalities in the endothelium that may account for the migraine headaches and risk of stroke associated with SIOD. Once they understand what is going wrong with the function of the endothelial cells, Dr. Lewis and his team hope to screen for potential drug treatments to prevent families from facing this frightening experience.

This first-of-its-kind research is fueled by collaborations across Stanford's campus, all made possible by you. 


Dr. Lewis' vision to identify a therapeutic treatment for SIOD within the next two years will require two important steps.

Publishing Novel Results
We must reduce SIOD's complex disease process to the point where researchers can use the CRISPR-edited cell lines to screen potential therapies. In the next year, once the preliminary findings from the cell models are robust and reproducible, Dr. Lewis aims to publish his lab's key findings. 

This is a necessary and critical step in order for the team to apply for additional grants to supplement your incredible philanthropy and accelerate progress toward a therapy for SIOD. 

Screening Potential Therapies
With grant support from institutions like the National Institutes of Health (NIH), the Lewis Lab will begin screening potential drug candidates for SIOD. To provide clinical benefits on a quicker timeline, the lab will start by screening existing compounds that have already been safely used in human clinical trials or that are FDA-approved, a process that Dr. Lewis estimates will take up to a year. 

If an existing drug is not identified as an effective treatment for SIOD, the lab will join forces with academic and industry partners to pursue novel drug therapies. 

Your philanthropy is creating a lasting ripple effect.


Once we identify the disease processes of SIOD, there is hope that the same processes will apply to many other diseases. If we can understand, for example, why blood vessels do not function normally in SIOD, we can apply that knowledge to treat other blood vessel disorders that elevate the risk of stroke. The same can be said for each of the organ systems affected by SIOD, including the kidneys, immune system, heart, and lungs. As we continue our pursuit of treatments for children like Kruz and Paizlee, the discoveries we make have the potential to improve the lives of countless kids and families at Packard Children's and beyond.

June 15, 2022 Publication - New England Journal of Medicine Publication

Sequential Stem Cell–Kidney Transplantation in Schimke Immuno-osseous Dysplasia

Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. 

Each patient received sequential transplants of αβ T-cell–depleted and CD19 B-cell–depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.)

Read Previous Years Updates

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