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Venomous Fish Peptide Controls Asthma Lung Inflammation in Mice

Diagram and images of T. nattereri and it's venom-delivering spines.
T. nattereri has four spines. It ejects venom through these spines when threatened by a predator, causing intense pain, swelling, and potentially necrosis. Credit: Mônica Lopes-Ferreira/CeTICS
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A study from the São Paulo Research Foundation (FAPESP) has found that a peptide produced by the venomous toadfish Thalassophryne nattereri can control lung inflammation in mouse models of asthma. The research is published in Cells.

Searching for therapeutic peptides

T. nattereri is a small fish species native to coastal waters in north and northeast Brazil that produces venom as a defensive weapon against predators. Venom glands at the base of its fins are connected to four spines – two on the top of its body and one on each side. When touched or stepped on, the spines penetrate the victim and inject venom that causes pain, swelling and potentially the death of tissue around the wound (necrosis).

Dr. Mônica Lopes-Ferreira, a biologist at the Center for Research on Toxins, Immune Response and Cell Signaling (CeTICS) funded by FAPESP, has been investigating and characterizing T. nattereri peptide (TnP) for almost three decades.

Many other peptides from bacteria, fungi, plants and animals have attracted attention from researchers as potential therapeutic candidates for immune-mediated chronic inflammatory diseases. Such peptides may have better therapeutic properties than their human versions, including improved selectivity, potency and stability.

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“We started studying the venom of T. nattereri in 1996 because we wanted to analyze its toxins in order to develop a treatment for people injured in accidents,” said Lopes-Ferreira. “We were surprised to discover a small molecule, a peptide, that our studies here at the laboratory showed to have anti-inflammatory properties. An entirely novel molecule no one had ever discovered.”

Lopes-Ferreira’s group has previously studied the effects of TnP in animal models of autoimmune and inflammatory diseases. In the current study, they investigated whether oral TnP treatment is effective in controlling symptoms and immune responses in a mouse model of asthma.

TnP in mouse models of asthma

The researchers treated mice with TnP and found no evidence of airway hyperreactivity or lung remodeling (structural changes caused by asthma that lead to thickened and narrowed airways and impair lung function).

Lopes-Ferreira and colleagues also found that TnP acted on secondary lymphoid organs, such as the spleen and lymph nodes, as well as locally in the lungs. Here, TnP inhibited the production of inflammatory cytokines – signaling molecules secreted by immune cells that promote inflammation. TnP treatment also prevented abnormal increases in the production of mucus-producing cells (hyperplasia) and decreased the thickening and deposition of collagen that can lead to lung stiffness in asthma.

“Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma,” the authors write in the paper.

“Many diseases cause inflammation. We chose asthma to test TnP using animal models in the laboratory and concluded that it was safe and efficacious. It improved the lung inflammation caused by asthma. This is a Brazilian discovery and we’ve taken care to protect it by filing for a [patent],” said Lopes-Ferreira. “We now mean to continue with the research. The more we discover, the more we’ll know about the diseases TnP can treat. It will also be very important to partner with a pharmaceutical company that wants to invest in TnP so that a medical drug can be developed.”

Reference: Lima C, Falcão MAP, Pinto FJ, Bernardo JTG, Lopes-Ferreira M. The anti-inflammatory peptide TnP is a candidate molecule for asthma treatment. Cells. 2023;12(6):924. doi: 10.3390/cells12060924

This article is a rework of a press release issued by FAPESP. Material has been edited for length and content.