Researchers at the University of California, Los Angeles (UCLA) have made a groundbreaking discovery that could revolutionize the treatment of chronic kidney disease (CKD). A study published in Science Translational Medicine has uncovered a critical factor that determines how much scarring occurs following kidney injury, leading scientists to identify a potential precision medicine approach to prevent CKD progression.

The researchers, led by Dr. Arjun Deb, found that type 5 collagen – a minor component of scar tissue – plays a crucial role in maintaining the structure and function of scar tissue. They discovered that differences in type 5 collagen expression help explain why some people develop more extensive kidney scarring than others.

This breakthrough has significant implications for the treatment of CKD, which affects over 800 million people worldwide. Currently, there are no therapies that directly target or reverse fibrosis, a process that impairs the kidneys’ ability to filter toxins from the blood and reabsorb water, often leading to kidney failure.

The study involved analyzing data from the UK Biobank, a long-term study tracking more than 1.5 million people. The researchers found that expression of Col5a1, the gene encoding type 5 collagen, strongly correlated with the risk of developing CKD over the course of a decade.

A series of experiments in mouse models confirmed these findings: Mice with low Col5a1 developed more severe fibrosis and progressed more rapidly to kidney failure following kidney injury. As with humans, type 5 collagen was playing a crucial role in maintaining the structure and function of scar tissue.

The researchers identified a potential solution in Cilengitide, a drug that disrupts integrin signaling. They found that treating animals with decreased type 5 collagen with Cilengitide significantly reduced kidney fibrosis and slowed disease progression. Notably, it had no effect in mice with normal Col5a1 expression, highlighting its potential as a targeted therapy for individuals at risk of rapid disease progression.

This presents an exciting opportunity to potentially repurpose this drug, which was already deemed safe by the FDA, for a completely different indication.

The researchers are now working to establish a blood test to measure Col5a1 levels in human patients with CKD to establish a clinical threshold for identifying at-risk individuals. If validated, this biomarker could be used to guide treatment decisions, pinpointing patients who could benefit from this targeted approach to slowing disease progression.

Beyond CKD, the researchers are also investigating whether the same mechanisms contribute to fibrosis in the liver and blood vessels, where scarring is a major driver of disease.

The use of Cilengitide has not been tested in humans as a treatment for excessive scarring and has not been approved by the Food and Drug Administration as safe and effective for this use. This novel therapeutic approach is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California.

The study’s findings have significant implications for the treatment of CKD, and further research is needed to validate these results and explore their potential applications in humans.

The fight against inflammatory lung diseases has taken a significant turn with the discovery of a groundbreaking approach to treating pulmonary sarcoidosis. This condition, characterized by granulomas – tiny clumps of immune cells that form in response to inflammation – affects around 200,000 patients in the U.S. and has been largely unchanged for the past 70 years.

In a recent study published in Science Translational Medicine, scientists at Scripps Research and aTyr Pharma have identified a protein called HARSWHEP that can soothe the inflammation associated with sarcoidosis. By regulating white blood cells, HARSWHEP reduces inflammation, slowing the disease’s progression and resulting in less scarring.

The key to this discovery lies in HARSWHEP’s gentle nature. Unlike other treatments that suppress the immune system, HARSWHEP “nudges” it in a certain way, quieting the inflammation without causing significant harm. This approach has shown promising results in a phase 1b/2a clinical trial of efzofitimod, a therapeutic form of HARSWHEP.

Researchers believe that HARSWHEP could be used to treat other interstitial lung diseases (ILDs), a family of conditions characterized by inflammation and scarring of the lungs. While more research is needed, this breakthrough offers new hope for patients suffering from these debilitating diseases.

The study’s senior author, Paul Schimmel, Professor of Molecular Medicine and Chemistry at Scripps Research, says that the results validate a new way to approach immune regulation in chronic lung disease. His colleague, Leslie A. Nangle, Vice President of Research at aTyr Pharma, adds that HARSWHEP’s mechanism of action is unique and has never been characterized before.

The team’s findings have significant implications for patients with ILDs. Current treatments often involve long-term steroid use, which can lead to weight gain, organ damage, and increased vulnerability to infection. By providing an alternative treatment option, HARSWHEP could improve the lives of those affected by these conditions.

As researchers continue to explore the potential of HARSWHEP, this breakthrough serves as a reminder that even in the face of seemingly insurmountable challenges, innovative approaches can lead to groundbreaking discoveries.

A groundbreaking study published in the European Respiratory Journal has shed new light on the devastating lung disease Idiopathic Pulmonary Fibrosis (IPF). Researchers from Rutgers Health have identified networks of misplaced immune cells driving this aggressive condition, potentially opening a path to new treatments for IPF patients.

For decades, scientists have struggled to understand the underlying mechanisms of IPF, which scars lung tissue and makes breathing increasingly difficult until patients can’t get enough oxygen. The available drugs provide minimal benefit, and lung transplantation works for some patients, but transplants have a 50% five-year mortality rate.

The study used advanced spatial mapping techniques to compare healthy lung tissues and tissues from patients with fatal IPF. The researchers discovered that disease-scarred lung tissue abounds in plasma cells – specialized immune cells that typically reside in bone marrow and produce antibodies. This was a striking finding, as normal lungs have almost no plasma cells.

The researchers identified previously unknown cellular networks orchestrating this abnormal immune response. They discovered novel mural cells wrapping around blood vessels and producing signal proteins that organize immune responses. Unique fibroblasts secreting a protein that attracts plasma cells to damaged areas were also found.

This particular type of fibroblast has never been described before, and its role in scarring is still unknown. However, the researchers believe that targeting these abnormal cellular networks may prove an effective disease treatment in humans.

The research team began using live mice to see if reducing plasma in the lungs slowed disease formation. This work demonstrated that blocking signaling pathways reduced plasma cell accumulation and alleviated lung scarring. The findings suggest that drugs targeting plasma cells already exist, which could potentially be repurposed to treat IPF.

For patients with IPF, the findings offer hope of new treatments for a debilitating condition with limited therapeutic options. The disease typically affects men over 60 years of age, with most patients dying within five years of diagnosis.

The next steps for the research team include determining whether the plasma cells are producing autoantibodies against healthy tissues and further investigating how fibroblasts and mural cells develop their abnormal properties in IPF. This study represents a collaborative effort between the Child Health Institute of New Jersey and the Rutgers Institute for Translational Medicine and Science, combining mouse model research with analysis of human lung tissue from end-stage IPF patients.

“Our research suggests that IPF might have a strong autoimmune link,” said Qi Yang, an associate pediatrics professor at Rutgers Robert Wood Johnson Medical School.