Tag: fibrosis

Categories : Diseases, Syndromes and ConditionsTags :

Researchers Develop Nanoparticle Therapeutic for Fibrosis

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Credit: Scientific Animations CC4.0

Researchers at The University of Texas at El Paso are developing a new therapeutic approach that uses nanoparticles for the treatment of skin and lung fibrosis, conditions that can result in severe damage to the body’s tissues.

Md Nurunnabi, PhD, is an associate professor in UTEP’s School of Pharmacy and the lead researcher on two studies published this June in the Journal of Controlled Release; one study focuses on skin fibrosis and the other on lung fibrosis.

“We are closer than ever to developing a safe, effective and reliable approach to treating fibrosis,” Nurunnabi said.

Fibrosis is a condition in which the tissues in an organ become thicker and stiffer, Nurunnabi says. This can have multiple damaging effects, such as the lungs not being able to hold enough oxygen or blood vessels becoming narrower, leading to high blood pressure.

“I studied fibrosis during my postdoctoral training but became interested in focusing on it in my lab during the COVID-19 pandemic,” Nurunnabi said. “I observed that many people were passing away not because of COVID itself, but because of the inflammation and fibrosis caused by the viral infection in the lungs. Our lab focuses on developing nanotechnology that can target specific cells.”

Fibrosis can occur as a side effect of chemotherapy or the result of a viral infection or autoimmune disease, a condition in which the body’s immune system attacks its own cells. For example, with an autoimmune condition, the body kills fibroblasts, the cells that help form connective tissue. The body then produces more collagen than it needs, which leads to fibrosis.

Nurunnabi’s team focused on designing a nanoparticle that could target the cells that are responsible for fibrosis development and progression without disturbing the “good” cells necessary for the body’s healthy functioning. Rather than killing the ”bad” cells, the team was successful in modifying them so that they no longer produced excess collagen, in effect rehabilitating the cells. The studies were conducted in the test tube and in mice.  

“Dr Nurunnabi’s research into skin and lung fibrosis sheds light on the devastating impact of these conditions, whether acute or chronic,” said José Rivera, PharmD, founding dean of the School of Pharmacy. “His findings offer hope for improved treatments that could significantly increase life expectancy and enhance the quality of life for affected individuals.” 

Source: University of Texas at El Paso

Categories : New Compounds and TreatmentsTags :

Immunotoxin Treatment Stops Liver Fibrosis

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A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes). Credit: Dr. David Kleiner, National Cancer Institute/NIH
A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes). Credit: Dr David Kleiner, National Cancer Institute/NIH

A new study successfully used immunotoxins to prevent the progression of liver fibrosis by targeting a protein specific to that disease.

Fibrosis, the buildup of collagen and scar tissue, can be caused by alcohol abuse and disease. University of California San Diego School of Medicine researchers and their collaborators are looking for ways to treat fibrosis by preventing liver cells from producing collagen. 

“So we thought…what if we take immunotoxins and try to get them to kill collagen-producing cells in the liver,” explained team lead Tatiana Kisseleva, MD, PhD, associate professor of surgery at UC San Diego School of Medicine. “If these antibodies carrying toxic molecules can find and bind the cells, the cells will eat up the ‘gift’ and die.”

The study focussed on immunotoxins designed to bind a protein called mesothelin, which is rarely found in the healthy human body. The protein is only produced by cancer cells and collagen-producing liver cells, known as portal fibroblasts.

Kisseleva teamed up with co-author Ira Pastan, MD, at the National Cancer Institute, part of the National Institutes of Health (NIH). Dr Pastan is co-discoverer of mesothelin and an expert on using immunotoxins to target the protein on cancer cells, and he leads several clinical trials using it in treating patients with ovarian cancer, mesothelioma and pancreatic cancer.

Since the immunotoxins specifically recognise human mesothelin, the researchers couldn’t use a traditional mouse model of liver fibrosis. So, they transplanted human liver cells isolated from patients to mice and treated them with the anti-mesothelin immunotoxin. Compared to untreated mice, 60 to 100 percent of human mesothelin-producing cells were killed by the immunotoxins, which also reduced the deposition of collagen.

Liver fibrosis treatment is very limited at present, with weight loss being currently the only known method for reducing liver fibrosis associated with non-alcoholic fatty liver disease. Alcoholic liver disease is most commonly treated with corticosteroids, but they are not highly effective. Early liver transplantation is the only proven cure, but it is rarely available.

“What we want to know now is, can this same strategy be applied to other organs?” Dr Kisseleva said. “Surprisingly enough, the same cells are responsible for fibrosis in the lung and kidneys. This is especially exciting because we already know from Dr Pasten’s cancer clinical trials that anti-mesothelin immunotoxins are safe in humans, potentially speeding up their application in other areas.”

The findings were published in Proceedings of the National Academy of Sciences

Source: University of California San Diego

Journal information:Nishio, T., et al. (2021) Immunotherapy-based targeting of MSLN+ activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis. PNAS. doi.org/10.1073/pnas.2101270118.