Inflammatory research

IF YOU’LL PARDON the pun, inflammation has become a hot topic in recent years. Research is pointing to the body’s inflammatory response as a factor involved in more and more conditions, including arthritis, cancer, diabetes and heart disease.

So there’s a drive on to come up with more effective and targeted ways of controlling the body’s immune response that can dampen down inflammation that has gone awry. And a new project is looking for clues in nature – more specifically in parasites and plants found in Brazil.

“The goal, broadly speaking, is to discover new therapies for inflammation,” says Luke O’Neill, professor of biochemistry at Trinity College Dublin and director of the Trinity Biomedical Sciences Institute.

His group is part of a European-Brazilian consortium that’s looking for potential new therapies or drug targets in plant species and parasitic ticks. In particular, they are focusing on an aspect of inflammation called resolution – the repairing phase.

“Resolution has become the trendy part of inflammation,” says O’Neill. “When you have an inflammatory reaction – let’s say you get an infection in your skin – you kick off a big inflammatory response, the bug gets killed hopefully, and then you resolve the whole thing and you repair. A new way to look at inflammatory diseases isn’t so much that they are overactive inflammatory events, it’s more there’s a defect in repair.”

Offering arthritis as an example, he says: “Some people call arthritis the wound that never heals. There’s a wound there, and normally the inflammatory process would heal that wound – that is what inflammation is there for – but for some reason it becomes defective and we still don’t know why.”

So how can ticks and plants from South America help? The new Timer (Targeting novel mechanisms of resolution in inflammation) project hopes to find out, by seeing if certain species contain agents that affect resolution.

“We have worked with molecules from plants and parasites for a while now,” says Dr Mauro Teixeira from the Federal University of Minas Gerais in Brazil, an investigator on the project.

His group has already identified proteins from blood-sucking ticks called evasins that seem to have an anti-inflammatory effect.

“We have also done some initial screening of biological activities from plant extracts,” he explains, describing how the plant species come from not from the Amazon but the Cerrado region, a biosystem in the centre of Brazil.

The group chose not to go the route of mining into tribal or native expertise about plants, but rather went on more “common knowledge”, explains Teixeira.

“According to Brazilian law, any molecule or knowledge which derives from research from tribal knowledge has to be returned for them,” he says. “That actually sounds very nice, but also means that it is incredibly difficult to do research with tribal knowledge or to access this knowledge. authorisations are needed. We have not taken that approach. Instead, we have used plants which are common knowledge in our state.”

It is still common for people to drink infusions made from different plant parts, he notes. “It is not difficult to go to markets and find people who sell plant parts to be used for infusions. So we did not really spent much time doing ethnopharmacological work (for legal reasons), but chose a system in which we could screen any plant with potential anti- inflammatory activity.”

The Timer project is analysing extracts derived from particular plants to look for effects on inflammation, and to help identify the mechanisms of some molecules that have already been identified.

“By combining state-of-art screening, chemical, and molecular biology techniques, we hope to come up with novel molecular leads for development against chronic inflammatory and auto-immune diseases,” says Teixeira.

The five-year project, which is being funded to the tune of €3 million under the EU Framework Programme, involves several partners in Brazil and Europe, including Trinity.

O’Neill’s group is bringing their expertise on immune molecules and potential regulators to the project, and he describes the overall approach as being like a screen for potential new therapies and targets.

More generally, he nods to the potential of the enormous biodiversity in Brazil to be home to molecules with potential. “This is like a sweet shop of opportunity,” he says. “The plants have done the pharma for us. You have a natural factory full of chemicals there and the plants have done all the hard work.”