A new drug promises to curb multiple sclerosis, Parkinson's and Alzheimer's

Researchers at University College London and Loyola University have developed a modified compound of cyclosporin A that blocks cyclophilin D in the brain, offering a new avenue for treating neurodegenerative diseases. Early animal studies show promising results

La multiple sclerosis It is a disease that mainly affects young adults; in fact, it is one of the main causes of disability in this population group. It is characterized by a attack of the immune system itself on myelin, protective layer that covers nerve fibers in the brain and spinal cord.

We can imagine the myelin Like the insulation of an electrical wire, its function is to allow signals between neurons to travel quickly and efficiently. When this protective layer is damaged, the “wire” begins to fail. As a result, the body loses its ability to control certain movements, thinking becomes altered, and vision problems appear.

At the cellular level, mitochondria – the “energy powerhouses” of cells – are also affected in cases of multiple sclerosis. cyclophilin D, an enzyme found inside mitochondria, plays an important role in the progression of the disease. This enzyme helps open a channel called the “mitochondrial permeability transition pore,” which causes further damage to neurons. For this reason, cyclophilin D is a key target for developing new drugs that can slow the progression of multiple sclerosis.

How does the new compound work?

And that is precisely what cyclosporine A is for, which is capable of block cyclophilin D. However, this drug is not very useful in clinical practice, as it does not reach sufficiently high levels in the brain, even when administered intravenously.

Drugs like cyclosporine A, which have complex structures (known as macrocyclic peptides), face a major challenge: they cannot easily cross the so-called blood-brain barrier, which acts as a shield protecting the brain and making it difficult for many drugs to enter.

In order to try to solve this problem, a group of researchers from University College London (UCL) and Loyola University, together with other institutions, decided modify the structure of cyclosporine A by adding an additional portion with a delocalized (distributed) positive charge that facilitates the accumulation of the drug in the mitochondria, whose internal charge is negative.

Furthermore, this modification allows the drug to cross the blood-brain barrier more easily and reach the nervous system effectively.

The new compound not only blocks the activity of cyclophilin D, but also It reaches brain concentrations 20 times higher than its previous versions or unmodified cyclosporine A. It is a fundamental improvement for treating diseases that directly affect the nervous system.

Studies on how this molecule is absorbed and processed in the body have shown that single dose maintains elevated levels in the brain for at least 48 hours, suggesting a long-lasting effectiveness.

Beyond multiple sclerosis

Cyclophilin D inhibitors may not only be effective in treating multiple sclerosis, but have also shown utility in other central nervous system diseases such as Parkinson's, Alzheimer's and amyotrophic lateral sclerosis. This suggests that there is a common cause for all these diseases, which is represented by damage to the mitochondria of neurons.

Additionally, this new technology, which adds a delocalized positively charged moiety to certain drugs, could facilitate the access of other drugs with complex structures to the central nervous system.

Collaboration is strength

The discovery is the result of a interdisciplinary approach which combines knowledge of chemistry, biology and medicine, a field known as pharmaceutical chemistry. Pharmaceutical chemistry is concerned with designing and developing new drugs and improving the way these compounds are absorbed and distributed in the body.

This approach makes it possible to address the challenges posed by diseases as complex as multiple sclerosis and other neurodegenerative pathologies.

Although Further studies and clinical trials are still needed to confirm the effectiveness of the new compound in humans, The preliminary results in animal models are very encouraging. These results could open up new avenues for treating not only multiple sclerosis, but also other diseases that affect the brain.

Source: The Conversation