RESEARCH PRIORITIES

Families of individuals with SATB2-associated syndrome (SAS) recognize the importance of research to better understand SAS and identify possible treatments.

The SATB2 Gene Foundation has created a powerful research asset by developing induced pluripotent stem cells (iPSCs) from patient cells. iPSCs provide cellular models of disease to rapidly advance knowledge and discovery.

Based on high impact needs identified by a recent independent scientific analysis and caregiver input, we have prioritized the following areas in SAS research:

  • speech and language
  • behavior
  • sleep
  • global developmental delays

Additional research priorities include projects on SATB2 function and expression, variations in clinical phenotypes, and symptomatic and/or curative therapeutic interventions.

SAS Stem Cell Biobank

The advantage of a Foundation-sponsored stem cell biobank is that the cell lines will not be held as proprietary by any single laboratory, and we can therefore share iPSCs with qualified researchers around the world in order to continue to advance SAS research. These cells allow researchers to advance our understanding of human-specific disease phenotypes (patient characteristics) and test potential treatments. We have a total of 8 iPSC lines available (4 patient and 4 control lines) through an application and Material Transfer Agreement (MTA).

Experiments with iPSCs typically involve differentiating the stem cells into specific cell types including specific neuronal subtypes (brain cells). These cells allow researchers to study disease mechanisms, for example, how different alterations of the SATB2 gene change neurons derived from iPSCs, and study the effect of the drugs on different cell types, such as neurons derived from iPSCS. This is a necessary first step towards evaluating potential treatments. 

How You Can Help

CURRENT RESEARCH

We need YOU, parents and caregivers, to help move research FORWARD! Join Dr. Yuri Zarate’s SATB2 clinical registry. We need to fully understand SATB2-associated syndrome in order to develop treatments and recommendations for clinical care. Without rare disease registries such as this one, we would not understand the natural history of these rare conditions. Learn more here or by emailing Dr. Zarate today.

The Cebrebra Network for Neurodevelopmental Disorders in the UK has been profiling the behavior phenotype of SATB2-Associated Syndrome. The next phase of research is funded by the Baily Thomas Foundation and will involve in-depth study of behaviors that challenge in SAS. The overarching aim is to understand the contribution of health-related difficulties, autism symptomology, sleep disturbance and mental health difficulties to the development and maintenance of behaviors that challenge in SAS. Read more about the preliminary findings here.

Updated: November 2021

Interview Study: Behaviours that Challenge in SATB2-associated syndrome

Researchers at Aston University are conducting an interview study that aims to find out more about behaviours that challenge in SATB2-associated syndrome.

To read the full recruitment announcement, click here.

The Arkansas Children’s Hospital is recruiting individuals with SAS who are 13 years old and older to participate in a study to learn more about what it looks like to be an adolescent and/or adult with SAS. If your child or loved one qualifies and you are interested in participating, please email Katie Bosanko. The individual must be enrolled in the SAS Clinical Registry to participate. If they are not enrolled, we can easily enroll them into the registry first.

To add additional opportunities and information, please email us today!

RESEARCH AWARDS

Bone geometry deficits in individuals with SATB2-Associated Syndrome.

Awarded $6,580.20

SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the SATB2 gene. Bone problems such as leg bowing, abnormal curvature of the spine, and fractures have been reported in individuals with SAS. From previous studies, it is also known that individuals with SAS often tend to have weaker bones as documented by x-rays dedicated to measuring bone strength, regardless of the type of genetic change in the SATB2 gene.

To date, the research studies involving bone strength in children with SAS have exclusively utilized a type of x-ray called DXA scan. This study while useful and routinely used, is unable to precisely locate if the deficiency is located in the outer part of the bone (cortical or compact bone, the inner part (trabecular or spongy bone), or both. In this study, we will be using a portable type of X-ray machine that is more accurate in analyzing bone strength call peripheral quantitative computed tomography (pQCT). This technique takes images in a matter of minutes and the results allow us to see what part of the bone is weaker. We will not be evaluating the utility of the pQCT to determine where the bone is weaker but also if it has a higher ability to detect early problems compared to the standard DXA scan.

As part of this study, we will also be evaluating the levels of several bone health markers in the blood to see how they relate to the x-ray findings and if they can be used in routine care of individuals with SAS to predict bone complications.

We expect this study will allow us to gain added insight regarding the bone problems seen in SAS that might contribute to the increased risk for bone fragility in this population while providing better surveillance and management recommendations.

Delineating the regulatory landscape of SATB2-Associated Syndrome.

Awarded $19,708

Gene expression is tightly regulated and involves several (non-coding) key elements such as the promoter anddistal regulatory elements, the enhancers. To switch on the expression of a gene, these enhancer elements physically interact with the promoter of the gene by looping out the intervening DNA sequence.

Recently, we performed an extensive literature review to shed more light on the importance of noncoding structural variations (SVs) in neurodevelopmental disorders (NDDs) (D’haene et al., 2020). In this review we discuss a comprehensive collection of noncoding SVs being at the root of the NDD phenotype in the reported patients. One of the regions in which several noncoding SVs associated with a NDD, have been reported, is the intergenic region downstream of the SATB2 gene.

Previously we determined the interacting elements with the SATB2 promoter. With this proposal we want to determinethe enhancer activity of these interacting regions. We will make use of both in vitro (luciferase assays) and in vivo (zebrafish) assays. The data generated in this project could lead to a better understanding of how SATB2 expression is regulated and subsequently of the causal effect of noncoding SVs in this region. Moreover, these data will be an asset to interpret noncoding variation (in whole genome sequencing (WGS) patient data) in the region downstream of SATB2. In addition, the enhancers that might be validated during this project, are of interest for further research to determine the potential of CRISPR-based strategies targeting these regions to boost SATB2 expression.

Assessment of energy production pathways, metabolism, and hormonal response in SATB2-Associated Syndrome.

Awarded $12,442.28

This study will look at metabolism and hormone response differences in cells from individuals with SAS compared with controls. A series of experiments will evaluate energy metabolism pathways and responses to different concentrations of some hormones by using the Phenotype Mammalian MicroArray (PM-M) platform developed by Biolog™. The utility of this tool has been demonstrated in various neurodevelopmental conditions, in some cases leading to the identification of useful interventions. The investigators hope to identify some potential energy pathways that may play a critical role in how SAS affects individuals and will attempt to develop a profile for individuals with SAS that could be distinctive compared to controls.

Determining SATB2-mediated gene expression in human hippocampal neurons.

Awarded $12,500.00

Research in the Fish lab uses animal (mouse) and cell (mouse and human) models of SATB2-associated syndrome (SAS) to understand the molecular and cellular mechanisms underlying skeletal and neuronal defects typical of SAS. This study will identify changes in gene expression and major gene regulatory pathways altered in neurons among isogenic stem cells with SATB2 mutations (generated with CRISPR/Cas9). A major goal of this project is to identify regulatory pathways that could represent therapeutic targets for SAS patients and will lay the groundwork for future experiments using human induced pluripotent stem cells (hiPSCs) derived from SAS patients.

IPSCS BANK

The SATB2 Gene Foundation requires all applicants for the iPSC (Induced Pluripotent Stem Cells) bank to complete the application and agreement, along with the iPSCs Bank Material Transfer Agreement, in order to access and use the iPSC Bank biological materials. Only SGF approved applicants may have access to the materials. These materials are for research purposes only and are not transferable to any non-approved third party.

Step 1: Complete the application and material transfer agreement (MTA). In addition to the application and MTA, submit the following supporting materials:

a. Lay Statement for the SATB2 Gene Foundation. In a brief paragraph of approximately 10 lines, describe your proposal and it’s significance.

b. Provide a short scientific description of the research you will conduct using these Materials and time frame for proposed completion. An abstract from a research grant is acceptable.

Step 2: Return the completed application, MTA, and supporting materials to the SATB2 Gene Foundation to research@satb2gene.org. Once approved by the SATB2 Gene Foundation Board of Directors, you will receive an email confirming your order.

Step 3: Shipping confirmation. Dr. Jennifer Fish’s laboratory is currently distributing iPSCs. Her laboratory will email you when the sample has shipped, with shipping and tracking information.

Step 4: Shipping charges. Shipment will be charged to the applicant-provided shipping carrier account.

Details of available iPSCs:

iPSC Line ID Alteration Originating Cell Type
ID2 Intragenic deletion fibroblast
MID2 fibroblast
ID59 Nonsense fibroblast
MID59 fibroblast
ID100 Missense fibroblast
MID100
SATB22207  Truncating frameshift PBMCs
SATB8383 Control PBMCs
Download Application
Download MTA

2021 RESEARCH GRANT APPLICATION

The SATB2 Gene Foundation is pleased to announce our Research Grant Program. This grant program is open to research investigators affiliated with an academic institution, hospital system, non-profit institution, or other accredited research institutions based in the United States or internationally. Eligible applicants include post-doctoral fellows, clinical fellows, researchers, physicians, or other associated research professionals with faculty appointments or research positions.

The SATB2 Gene Foundation prioritizes the following areas in SAS research, based on high impact needs identified by a recent independent scientific analysis and caregiver input:

  • Speech and Language
  • Behavior
  • Sleep
  • Global Development Delays

Additional research priorities include projects on SATB2 function and expression, variants in clinical phenotypes, and symptomatic and/or curative therapeutic interventions.

Schedule for Grant Applications:

  • July 23, 2021: Program Opens

  • September 17, 2021: Full Applications Due

  • October 22, 2021: Award Announcements to Applicants

  • Late December 2021: Award Announcements to Public

  • Winter 2021: Anticipated Project Start

Applications will be reviewed by the SATB2 Gene Foundation Medical and Scientific Advisory Board and the Board of Directors. The grant selection process is unbiased and independent; awards are based solely on scientific merit and expected contributions to the priorities of the SAS community and body of knowledge about SATB2-associated syndrome. Advisors and board members with a conflict of interest will not participate in voting for those specific applications.

If you have any questions regarding the application process, please contact research@satb2gene.org.

Get Started:

HOW YOU CAN HELP

The SATB2 Gene Foundation needs your help in raising the necessary funds to continue to rapidly advance research.

Join us in making an impact on the future of SAS research.  Help us continue to fund innovative SATB2 research, including biobank expansion, experiments on biobanks samples, animal models, and clinical research with the SATB2 registry! Help us accelerate the pathway towards much-needed treatments for our SATB2 patients to improve their quality of life.

Please donate today to support research, on the online giving link please select “SAS Research” on the drop down menu. For additional information, please contact Allison Kaczenski.

Checks with a note of “Research” can mailed to the below address:

  • SATB2 Gene Foundation
    3050 Five Forks Trickum Road Suite D-524
    Lilburn, GA 30047 USA

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