Developing new treatments for complex diseases presents a myriad of challenges, ranging from understanding the disease’s mechanisms to ensuring the safety and effectiveness of proposed therapies. At Delta4, we’re passionately pursuing new treatments for Focal Segmental Glomerulosclerosis (FSGS). Leveraging our in-silico platform, Hyper-C, we’ve been able to identify new potential therapeutic options for FSGS. This process is especially intricate when it comes to diseases, like FSGS, with diverse causes and manifestations.
About Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is a histo-pathological diagnosis referring to scarring (sclerosis) in some segments of the kidney’s filtering units (glomeruli). FSGS is very heterogeneous in origin: it has many different causes including gene mutations, circulating factors, hypertension, immune dysregulation, as well as contributing environmental factors such as viruses or drugs.
FSGS is a progressive condition leading to proteinuria and nephrotic syndrome and can ultimately result in kidney failure. This then makes kidney replacement therapy (dialysis, kidney transplantation) mandatory, representing a huge burden for the patient and huge costs for the healthcare system.
While some individuals suffering from FSGS benefit from immunosuppressive therapies (corticosteroids or calcineurin inhibitors), these medications have strong side effects and don’t work for everybody.
Currently, there is no approved therapy specifically targeting FSGS. Moreover, this condition remains partially elusive. Therefore, there is a high medical need to provide novel therapeutic approaches.
Animal Models & FSGS
In this challenging context, once potential therapeutic candidates are identified, animal models emerge as an essential tool to further strengthen the hypothesis that the discovered treatment can work. Led by our Principal Molecular Biologist, Christoph Gebeshuber, Delta4’s team is already diligently utilizing this powerful tool.
Animal models are crucial for studying FSGS to better understand its pathogenesis and to develop potential treatments. Due to the many different pathogenic mechanisms for FSGS, not one optimal single model exists which would enable us to study every cause and aspect of this condition.
Here’s a summary for some commonly used FSGS models (groups):
- Toxin-induced nephropathy: Administration of the chemotherapeutic drug adriamycin (doxorubicin) can induce nephropathy, proteinuria and segmental sclerosis. Use of puromycin-aminonucleosid (PAN) is another option.
- Genetically modified mice: Mice with specific gene mutations, deletions or over-expressions have been engineered to mimic features of human FSGS and particularly to model the disease course for individuals with the same or similar issues. Examples include mutations in podocin or CD2AP, or over-expression of sUPAR or miR-193a.
- Nephrectomy: Surgical removal of 5/6 of the kidney tissue leads to increased filtration pressure in the remaining part, ultimately leading to proteinuria and kidney sclerosis.
There are certain challenges in developing optimal animal models. Given the multifactorial causes and diverse etiologies of FSGS, the importance of utilizing various models is evident.
Differences between humans and rodents in renal anatomy, physiology, immune responses etc. can limit the translational relevance of findings from animal studies.
Addressing and solving these challenges requires interdisciplinary approaches involving advanced genetic engineering techniques, innovative experimental models and setups, RNA sequencing from samples in humans suffering from FSGS etc.
Beyond the Horizon
As we navigate the complexities of developing new treatments for FSGS, the journey ahead is both challenging and hopeful. At Delta4, our commitment to addressing this critical medical need drives our relentless pursuit of innovation and discovery. With the aid of our in-silico platform, Hyper-C, we have identified a promising therapeutic candidate, marking significant strides towards a future where FSGS can be effectively managed.
The road to bringing these potential treatments to the clinic is paved with rigorous research and testing, particularly through the use of animal models. These models, as diverse as the disease itself, are crucial in unraveling the complexities of FSGS and ensuring the safety and efficacy of our discoveries. Led by Christoph Gebeshuber, our dedicated team is making progress in understanding FSGS’s pathogenesis and exploring innovative therapeutic options.
In the face of FSGS’s vast heterogeneity and the pressing need for effective treatments, Delta4 remains optimistic. Our work is guided by the principle that through perseverance, collaboration, technological and scientific excellence, we can make a tangible difference in the lives of those affected by this condition. The path to new therapies for FSGS is fraught with hurdles, but it is a path worth pursuing. With every discovery and every experiment, we move closer to a future where FSGS is no longer a daunting diagnosis but a manageable condition. Our journey continues, fueled by hope and the unwavering belief in the power of technology and science to change lives.
