Melitherapy: When the surface has deep implications

Many drugs that are available in the market have something in common, regarding how they make effect: they directly target one or more proteins. And this is not a coincidence. Proteins perform a vast range of functions within the cells of all living organisms that are key for them to work properly. These molecules are in charge of such vital tasks as forming structural tissue like collagen, facilitating biochemical reactions by acting as enzymes or receiving and sending signals that modulate gene expression in the cell. Because they have this central role, if proteins fail to do their job, they cause diseases. And that’s why the drug design process often involves inhibiting or modulating the activity of certain proteins, by binding them or by modifying their activity.

However, acting directly on proteins is not the only way to address the challenge of treating a disease. We want to introduce you to an innovative approach that targets a different cellular component: the lipids that form the cellular membrane. This approach is called Membrane Lipid Therapy, or melitherapy.

The human body contains billons of cells, and each one is surrounded by lipid membranes. These structures form a barrier that separates and defines cells and their internal organelles. Years ago, cell membranes were considered to be a mere physical feature that isolates the intracellular space from the outside. However, further research has shown that these features are involved in a lot of cellular functions. In fact, most of the cellular activity occurs within or around membranes: they are involved in vital processes such as controlling the traffic of molecules in and out of the cell, triggering cellular proliferation, changing the chemical signals that the cell emits to its environment or even modulating the process of cellular death.

Many of these functions are exerted through proteins that are embedded in the cell membrane and that establish chemical bonds with the lipids. In this location, proteins are integrated in a great range of signalling pathways that can go as deep as modulating cellular behaviour through changing the expression of certain genes.

That is why lipid composition of membranes can have an impact on these activities. While the basic structure of cellular membranes is a bilayer made of lipids, these can differ, and their relative abundance in the membrane can be different not only between cells, but between regions within the same membrane. These lipid variations can dramatically alter the physical properties of the cellular membrane and thus, the activity of the proteins within it.

A key membrane feature linked to lipid composition is fluidity, which refers to the mobility of the membrane components. This property depends directly on the ratio between two kinds of lipids, saturated and unsaturated, and determines how the lipids are packed: the tighter, the more proteins can be anchored to the membrane. For example, some membranes have compact regions known as lipid rafts that hold many signalling proteins and act as organising centres for signalling pathways. Reducing the membrane fluidity can dislodge proteins from the structure.

This is how Membrane Lipid Therapy can make the difference. In this approach, the therapeutic molecules are synthetic fatty acids that are designed to produce a change in the membrane lipid composition in order to modulate cellular processes. Membrane Lipid Therapy targets proteins in an indirect way: instead of binding to them directly, it disrupts their anchoring to the membrane.

This makes Membrane Lipid Therapy extraordinarily versatile. The onset of many different diseases is related to the malfunction of molecular pathways that work through membrane proteins. Some of them are serious conditions that are currently incurable, such as cancers, inflammatory or metabolic diseases or central nervous system illnesses like Alzheimer disease. But this approach is not limited to processes that involve proteins: any cellular activity linked to the composition of the lipid membrane can become a target of Membrane Lipid Therapy.

This innovative approach implies a “Copernican turn” that aims to mark the difference in how therapies are designed. Membrane Lipid Therapy has the potential to become a game-changing approach to provide an enormous improvement in the quality of life of many patients worldwide.