Melitherapy: lubricating the brain to cure complex neurological diseases

What if the key to treating Alzheimer's , epilepsy, or depression wasn't in genes or proteins, but in the fats that cover neurons?

For decades, research has focused primarily on studying defective proteins and genes as the cause of disease. Despite the scientific advances of recent years, we still lack truly effective treatments for many neurological pathologies.

Membrane Lipid Therapy ( MLT ) is a new field of biomedicine that seeks to treat diseases by modifying the lipids in brain cell membranes.

Lipids are not all the same: some, such as polyunsaturated fatty acids (including the famous omega-3s), can modify membrane structure and, therefore, alter the way proteins behave. This means that by adjusting the type of lipids present in the membrane, we could restore brain functions altered in various diseases. And the initial results are promising.

Synthetic lipids capable of integrating into the neuronal membrane and modifying its organization are already being developed. One of these compounds has been shown to restore the function of altered proteins in experimental models of Alzheimer's disease , opening up the possibility of recovering damaged neuronal circuits without altering DNA or directly manipulating the nervous system with invasive drugs.

But how is this achieved? We must keep in mind that neuronal membranes are not simple envelopes, but dynamic structures brimming with cholesterol, phospholipids, and fatty acids that influence communication between neurons (synapses), resistance to oxidative stress, cell survival, and many other key aspects of a cell's life.

When these lipids become unbalanced, neurons malfunction and various diseases arise. Melitherapy seeks to correct these imbalances through lipid modifications or readjustments of the cell's plasma membrane.

Here are some examples of melitherapy in action:

Alzheimer's: Recovering Connections

In this disorder, neurons lose cholesterol and certain phospholipids, which impairs the formation of synapses, the fundamental connections for neuronal communication and, therefore, for the functioning of the nervous system. A recent study showed that increasing omega-3 levels improves memory in mice. There are no conclusive results in humans yet, but drugs that stabilize neuronal membranes and could slow the cognitive decline that characterizes this disease are already being tested.

Epilepsy: Balancing lipids to reduce seizures

By repairing damaged neuronal membranes, drug-resistant seizures could be reduced. Studies show that adjusting brain lipids with omega-3s, such as DHA and EPA, decreases neuronal hyperexcitability, the state in which neurons become more prone to generating electrical impulses. Human trials are preliminary, but the combination with nanotechnology promises more precise treatments. This innovative approach could complement, and even replace, current treatments in cases of refractory epilepsy, where drugs fail.

Glioblastoma: Hopeful advances in the fight against the most aggressive brain cancer

A clinical trial has just yielded encouraging results for a lipid-based drug combined with radiation and chemotherapy to treat newly diagnosed glioblastoma, one of the most aggressive brain tumors.

Early data point to improved patient survival, especially in those with a genetic trait called methylation of the MGMT gene, which acts as a repair mechanism for damaged DNA. In most cases, this is beneficial, but in glioblastoma, it can help the tumor resist temozolomide . This is one of the most widely used treatments for this type of cancer and works by damaging the DNA of tumor cells. If MGMT is active, it repairs them, and chemotherapy loses its effect. However, when the gene is methylated—that is, deactivated—the tumor cannot defend itself against treatments.

In the study, the meliterapeutic drug was well tolerated and no new side effects were observed, suggesting a possible benefit for this group of patients.

Although this treatment sounds very promising, there are obstacles that must be overcome:

The blood-brain barrier: Many lipids can reach the brain from the blood, but some need to be bound to special transporters or vehicles, such as nanoparticles.

Side effects: To avoid unwanted effects, it is essential to design lipid molecules that act specifically on the organ or tissue being treated, without interfering with the normal functions of the rest of the body.

Personalization: Not all brains respond the same. Individualized therapies are needed for each patient.

And why is this therapy presented as a paradigm shift? Because it invites us to look at the brain from a different perspective. Instead of continuing to search for the "magic molecule" that explains the origin of so many neurological pathologies, perhaps we should accept that brain health also depends on the harmony between fats and proteins in a place as seemingly modest as the cell membrane. Right at that boundary between the outside world and the inside of the neuron may lie one of the keys to understanding and treating some of the most complex disorders of our time.

Article previously published in The Conversation

Enrico Castroflorio: Neuroscientist specializing in synaptic function and lipids, University of the Balearic Islands