[Capstone Project Spotlight] A Novel Therapeutic Strategy for Nephropathic Cystinosis

“Children born with nephropathic cystinosis now have new hope.”

Nephropathic cystinosis is a devastating genetic disorder affecting approximately 1 in 100,000 to 200,000 live births worldwide. By age 10, nearly 95% of children develop Fanconi syndrome, a severe kidney dysfunction causing excessive nutrient loss, dehydration, and stunted growth. Despite cysteamine, the only approved treatment, patients inevitably progress to end-stage renal disease (ESRD), facing a lifetime of dialysis or transplantation. While cysteamine helps reduce cystine accumulation, it does not address the underlying kidney damage driving disease progression. The UCSF Sarwal Lab, led by Dr. Minnie Sarwal, is pioneering a breakthrough therapy to protect and regenerate kidney function in this disease, and addressing the urgent need for timely diagnosis in kidney injury.

Dr. Minnie Sarwal, clinically trained pediatric and adult nephrologist with a PhD in molecular genetics, and a faculty in the Department of Surgery at UCSF, is the Co-Director of the Kidney and Pancreas Transplant Program. Dr. Sarwal runs an NIH funded translational lab at UCSF where the Sarwal Lab develops a new understanding on the mechanism of kidney injury in Nephropathic Cystinosis and proposed novel therapies to prevent kidney damage.

A New Therapeutic Approach

At the UCSF Sarwal Lab, lead researcher Dr. Swastika Sur, and other researchers have identified a unique critical pathway linked to the progression of cystinosis-related kidney damage, which remains untreated by current cysteamine therapy despite its ability to reduce cystine accumulation. They have also identified a small molecule compound that can correct this pathway, potentially slowing or stopping kidney damage. By utilizing a nanoparticle-delivered combination therapy, researchers at the Sarwal Lab aim to target both cystine accumulation and the underlying kidney dysfunction, offering a comprehensive treatment approach for nephropathic cystinosis and a transformative shift in disease management.

A Game-Changer in Kidney Disease Management

Cysteamine has long been the standard treatment for nephropathic cystinosis, yet it remains an imperfect solution. While it lowers cystine accumulation and slows progression to ESRD, it does not address the underlying kidney damage that ultimately leads to irreversible renal failure. The innovative combination therapy being developed at the UCSF Sarwal Lab addresses this critical gap by targeting both cystine accumulation and cellular injury, potentially eliminating the need for dialysis or kidney transplant. By correcting cellular stress and mitochondrial dysfunction, this therapy has the potential to treat patients with acute kidney injury (AKI) beyond cystinosis-related cases. To complement this treatment,the Sarwal Lab is also developing a novel assay for early detection of kidney damage in this disease, enabling timely intervention where current diagnostic methods fall short.

“ The innovative combination therapy being developed at the UCSF Sarwal Lab addresses this critical gap by targeting both cystine accumulation and cellular injury, potentially eliminating the need for dialysis or kidney transplant.”

Collaboration with the MTM Program

The Master of Translational Medicine (MTM) students play a vital role in advancing the combination therapy and developing markers to evaluate kidney injury and its reversal, which aim to revolutionize kidney injury treatment. Their contributions include conducting scientific experiments to validate therapy in in vitro models, analyzing market opportunities for kidney injury treatments, and assessing the intellectual property landscape. This semester, the team is preparing for animal studies, a critical step toward translating this research into clinical trials, bringing the potential therapy closer to real-world application and patient impact.

Looking Ahead: A Brighter Future for Cystinosis Patients

Children born with nephropathic cystinosis now have new hope. The breakthrough therapy the Sarwal Lab proposes not only reduces harmful cystine buildup but also helps repair damaged cells. This innovative approach could lead to better treatments for patients with this disease, prevent the development of kidney damage, and prevent or postpone end-stage renal disease, reducing patient morbidity and health care costs for kidney disease management. This approach is also broadly applicable to other causes of chronic kidney disease, resulting in a major positive clinical and fiscal impact for patients with kidney disease.

For those interested in learning more or collaborating on this initiative, Cystinosis, or kidney disease innovations, the UCSF Sarwal Lab can be reached at UCSF Medical Center at Parnassus. Contact Dr. Minnie Sarwal at Minnie.Sarwal@ucsf.edu to explore research opportunities and contribute to this transformative work.

The Sarwal Lab is also funded by the Cystinosis Foundation, Ireland and the Health Research Board, Ireland.