Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.
If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.
This week’s study is…
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization
We previously published about this research in a story titled “Researchers Use AI to Identify New Cystinosis Treatment Targets” which can be found here. The study was originally published in the scientific journal Nature Communications. You can read the full text of the study here.
This research team was associated with the ITINERARE University Research Priority Program at the University of Zurich, Faculty of Medicine at UCLouvain (Brussels), Microsoft Research-University of Trento Centre for Computational and Systems Biology, and Insilico Medicine.
What Happened?
Artificial Intelligence (AI) has been making a lot of headlines in the past year. New AI tools promise to change the way we work and create. But AI has been used for years to assist in medical research. In this study, the research team sought to use AI model systems in order to identify to therapeutic targets and possible therapies for kidney disease associated with cystinosis, a rare lysosomal storage disease.
The scientists partnered with the company Insilico Medicine, which harnesses AI for drug discovery. A critical component of the research was the company’s proprietary PandaOmics platform. Along with the use of model systems, the team was able to gain a greater understanding of the mechanism behind cystinosis kidney disease. More specifically, the team found that activation of a protein called mTORC1 appeared to play a role.
Cystinosis leads to the accumulation of cystine in various parts of the body, and this activates the mTORC1 protein. This abnormal activation of the protein can inhibit the differentiation and function of kidney tubular cells, triggering the symptoms of kidney disease. With this finding, the scientists continued their research in order to find a drug that could possibly be repurposed for treatment. They were able to identify rapamycin, a therapy already approved for other indications, as a potential option.
This conclusion was based on the drug’s target enzymes and structure, and prior studies have found rapamycin to be capable of improving lysosome and cell function. Further evaluation of rapamycin as a treatment for cystinosis in the clinical trial setting will reveal if it’s a good match.
About Cystinosis
Cystinosis is a type of lysosomal storage disease which is characterized by the abnormal accumulation of the amino acid cystine in the body. The disease is caused by mutations affecting the CTNS gene. This disease leads to the formation of cystine crystals in different areas of the body, particularly the cornea. Severe cystinosis can cause major symptoms early in life, such as kidney failure, growth and developmental impairments, diabetes, muscle atrophy, reduced skin and hair pigment, blindness, impaired sweating, and inability to swallow. Treatment of cystinosis includes cysteamine, which can impair the growth of crystals in the body; sodium citrate is also used to control blood acidity. If kidney failure occurs, dialysis and ultimately a kidney transplant are necessary for survival. To learn more about cystinosis, click here.
Why Does it Matter?
Kidney disease is among the most devastating impacts of cystinosis. Cystinosis kidney disease can progress rapidly to kidney failure, which can occur as early as age 10. This requires patients to use dialysis from a very early age while they wait for a kidney transplant, which comes with its own challenges.
“Children with cystinosis suffer from a devastating, multisystemic disease, and there are currently no available curative treatments.” – Olivier Devuyst, Head, Mechanisms of Inherited Kidney Disorders (MIKADO) group, Co-Director, ITINERARE University Research Priority Program, University of Zurich
A therapy that could slow or halt the progression of kidney disease in cystinosis would be a major breakthrough for patients and vastly improve their quality of life.
“Although the therapeutic benefits of this approach will require further clinical investigations, we believe that these results, obtained through unique interdisciplinary collaboration, bring us closer to a feasible therapy for cystinosis patients.” – Alessandro Luciani, Research Group Leader
