Fechtner Syndrome is a rare genetic disease both pathologically and phenotypically composed of hematologic, ocular, auditory, and progressive renal features. Protheragen is focused on developing therapeutic intervention for rare kidney disorders. Here, we provide our tailored service solutions for Fechtner syndrome.
Overview of Fechtner Syndrome
Fechtner Syndrome is a rare, autosomal dominant hereditary disorder that is part of the MYH9-related diseases (MYH9-RD) spectrum. It features a unique blend of macrothrombocytopenia—characterized by a paucity of large- sized platelets— along with the leukocyte inclusions (specifically, Döhle-like bodies in neutrophils) and sensorineural hearing loss. This is often accompanied by a progressive, proteinuric nephropathy that leads to end-stage renal disease (ESRD) replacing the kidneys' functional tissue. While the precise prevalence remains elusive owing to its rarity and heterogeneous presentation, it is believed to occur in 1 to 9 out of a million, with more than 300 pedigrees of MYH9-RD cataloged. Approximately 30% of patients with renal involvement typically present with proteinuria and the disease can lead to ESRD by the age of 35, intensifying the need for better healthcare.
Pathogenesis of Fechtner Syndrome
Fig.1 Schematic illustration of the MYH9 protein showing its domains and localization of p.Phe1446Leu mutation. (A. Pecci
et al., 2025)
Fechtner Syndrome is caused by MYH9 mutations that create a non-functional or misfolded form of NMMHC-IIA. In leukocytes, this abnormal protein aggregates and leads to the formation of Döhle-like inclusions. In the case of platelets, the mutations result in abnormal, oversized dysfunctional platelets, a condition known as macrothrombocytopenia. The kidneys are primarily affected in the glomeruli, where the mutant NMMHC-IIA causes damage to the glomerular filtration barrier, resulting in protein loss and progressive glomerulosclerosis. The combination of cellular malfunction and structural damage ultimately reduces the kidney's ability to filter blood, resulting in a progressive decline in kidney function, chronic kidney disease, and eventual renal failure. The differing clinical features and severity of a single syndrome, even within the same family, suggests additional genetic or environmental factors are also at play.
Therapeutics Development for Fechtner Syndrome
| Drug/Technology |
Target/Mechanism |
Key Progress |
Development Stage |
| Eltrombopag |
c-MPL receptor transmembrane domain (W499) |
Cohort study: bleeding risk significantly reduced in MYH9 patients |
Phase IV |
| Myosin allosteric modulators |
NMMHC-IIA α-helical pocket (L689-F705) |
Restores microtubule polarity in patient iPSCs |
Preclinical |
| Pirfenidone + SGLT2i |
1. TGF-β1 ligand
2. SGLT2 cotransporter |
Delays interstitial fibrosis (evidence extrapolated from Alport studies) |
Phase II |
| CRISPR-Cas9-MYH9 |
MYH9 exon 2 splice acceptor site |
Eliminates inclusion bodies in patient CD34+ cells in vitro |
Preclinical |
| AAV-NMMHC-IIA |
Secreted NMMHC-IIA |
Normalizes platelet morphology in murine models |
Preclinical |
| Lentiviral-HSC therapy |
AAVS1 safe harbor locus (19q13.42) |
Platelet counts restored in primate models |
Preclinical |
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 offers specialized services in developing advanced disease models for Fechtner syndrome, complemented by comprehensive preclinical therapeutic development. Our efforts are dedicated to deciphering the complex genetic and physiological factors that underpin this multi-systemic disorder and its associated renal complications.
Therapeutic Development Platforms for Fechtner Syndrome
Disease Models Development for Fechtner Syndrome
Protheragen provides innovative and comprehensive disease models to advance preclinical research into Fechtner syndrome. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the genetic predispositions and physiological dysregulations characteristic of Fechtner syndrome, supporting extensive drug discovery and mechanism-based investigations focused on platelet function, sensory organ integrity, and renal protection.
Cell-based & Organoid Models
- Patient-derived MYH9-R705H mutant podocytes
- iPSC-megakaryocytes with giant platelets
- Glomerular co-cultures
- MYH9-mutant glomeruloids
- Fibrotic nephron assembloids
Animal Models
- Human MYH9-D1424N transgenic mice
- Myh9-R702C knock-in rats
- Zebrafish myh9a knockout
- Xenograft platelet reconstitution 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 offers integrated preclinical development solutions specifically tailored for research in rare kidney diseases and conditions with significant renal impact, such as Fechtner syndrome. We provide expertise in comprehensive disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your therapeutic investigations from initial target validation to IND-enabling studies.
If you are interested in our services, please don't hesitate to contact us.
References
- McBane, R. D., et al. "Fechtner Syndrome: Physiologic Analysis of Macrothrombocytopenia." Blood Coagul Fibrinolysis 11.3 (2000): 243-7.
- Pecci, A., et al. "Myh9: Structure, Functions and Role of Non-Muscle Myosin Iia in Human Disease." Gene 664 (2018): 152-67.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
