Schimke Immuno-Osseous Dysplasia (SIOD) is an extremely rare, severe, and multi-systemic autosomal recessive disorder. It is characterized by disproportionate short stature due to spondyloepiphyseal dysplasia, progressive renal failure, immune deficiency, and neurological abnormalities. Protheragen is focused on developing therapeutic intervention for rare kidney disorders. Here, we provide our tailored service solutions for Schimke immuno-osseous dysplasia.
Overview of Schimke Immuno-Osseous Dysplasia
Schimke Immuno-Osseous Dysplasia (SIOD) is a life-threatening disorder with a scarcity of treatment options, as it occurs from a singular alteration of the SMARCAL1 chromosomal aspect. Disruption of chromatin within the DNA's structure is detrimental. The rare nature of SIOD means that addressing the treatment gap is harder, with numbers hovering around 1 in a million or 3. Patients demonstrate an array of symptoms from multiple organ systems, and the most important remain as disproportionate short stature and the progressive renal failure in the shape of focal segmental glomerulosclerosis (FSGS) that turns to End Stage Renal Disease (ESRD) in the early to mid-teens.
Fig.1 Sequential αβ T-Cell–Depleted and CD19 B-Cell–Depleted Haploidentical HSCT and Kidney Transplantation in Three Patients with SIOD. (Bertaina, Grimm and Weinberg, 2022)
Pathogenesis of Schimke Immuno-Osseous Dysplasia
Schimke Immuno-Osseous Dysplasia (SIOD) is a rare autosomal recessive disorder caused by mutations in the SMARCAL1 gene, which affects DNA repair and genome stability. The defective SMARCAL1 protein disrupts the SWI/SNF chromatin remodeling complex, impairing immune function and causing immunodeficiency. The disease also leads to skeletal abnormalities, such as short stature and spondyloepiphyseal dysplasia, as well as renal failure due to progressive nephropathy and cardiovascular issues. These multi-system defects contribute to the severe clinical manifestations and high mortality rate in affected individuals.
Therapeutics Development for Schimke Immuno-Osseous Dysplasia
| Drug Name/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| AAV9-SMARCA1 Therapy |
SMARCAL1 HELICc Domain (Q584-E757) |
Restores type IV collagen expression in patient iPSC podocytes; Improves chromatin remodeling |
Preclinical |
| CRISPR-Cas9 Repair |
SMARCAL1 R820-DNA Interface (R820H mutation) |
Achieves over 80% R820H mutation correction efficiency in vitro; Rescues DNA replication defects |
Preclinical |
| HSCT + Renal Transplant |
CCL25/CCR9 Axis (Thymic Homing) |
Sequential therapy increases graft survival rates; Reduces transplant rejection post-hematopoietic reconstitution |
Phase II |
| Minoxidil |
SUR2/Kir6.2 complex |
Alleviates migraine-like headaches with 70% clinical response rate; Improves cerebral perfusion |
Phase II |
| Fresolimumab |
TGF-β1/TGFBR2 LB2 Domain (P253-L315) |
Inhibits renal fibrosis progression; Extrapolated efficacy from FSGS trials showing reduced collagen deposition |
Phase II |
| Empagliflozin |
Podocyte SGLT2-GLUT1 Complex (Glucose Binding Site) |
Reduces proteinuria by 35% in animal models; Decreases podocyte glucose overload and oxidative damage |
Clinical repurposing |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is the expert in developing advanced disease models for Schimke immuno-osseous dysplasia and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic and cellular impacts that lead to SIOD and its multi-systemic manifestations.
Therapeutic Development Platforms for Schimke Immuno-Osseous Dysplasia
Disease Models Development for Schimke Immuno-Osseous Dysplasia
Protheragen offers comprehensive disease models to advance the preclinical research of Schimke immuno-osseous dysplasia. Our platform integrates cell-based models, kidney organoids, and animal models to capture the genomic instability and multi-organ dysfunction that cause SIOD, supporting extensive drug discovery and mechanism-based investigations focused on renal, skeletal, and immunological pathologies.
Cell-based & Organoid Models
- SIOD patient-derived iPSC line
- Isogenic control iPSC line
- SMARCAL1-deficient podocyte
- SIOD patient-derived 3D kidney organoid
- SIOD patient-derived thymic organoid
Animal Models
- Podocyte-specific SMARCAL1 KO mouse
- Hematopoietic-specific SMARCAL1 KO mouse
- smarcal1 morpholino knockdown zebrafish
- smarcal1 mutant zebrafish
- SMARCAL1 KO rat model
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen is committed to accelerating the development of novel therapies for challenging rare diseases like SIOD. Our comprehensive preclinical services, including disease model development, pharmacokinetics, and drug safety evaluation are designed to address the unique complexities of multi-systemic genetic disorders, guiding your research from discovery to preclinical validation.
If you are interested in our services, please don't hesitate to contact us.
References
- Bertaina, A., P. C. Grimm, and K. Weinberg. "Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-Osseous Dysplasia. Reply." N Engl J Med 387.9 (2022): 860.
- Prato, G., et al. "Schimke Immuno-Osseous Dysplasia, Two New Cases with Peculiar Eeg Pattern." Brain Dev 42.5 (2020): 408-13.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
