Lito Sousa has become the first person in the world to receive the test of the experimental substance ALN-6457, as an attempt to treat Creutzfeldt-Jakob disease. According to his wife, Mila Seidl, he remains in the Intensive Care Unit (ICU), showing stability and exhibiting no reactions after the administration of the product.
Currently, ALN-6457 has not yet been subjected to clinical trials in humans. The medical team plans to monitor possible changes in his clinical condition through tests conducted over the next six weeks.
This compound is developed by Regeneron, based in the United States, in collaboration with Alnylam Pharmaceuticals. It is important to note that the product still lacks complete clinical studies, and existing data are only preliminary.
The technology employed uses a molecule called siRNA, which functions to interfere with messenger RNA responsible for providing instructions for the production of the prion protein. In Creutzfeldt-Jakob disease, this protein can acquire an abnormal conformation, causing brain damage.
The therapeutic approach aims to reduce the amount of this protein. Theoretically, a decrease in the prion protein would result in less material available to form denatured versions of the protein.
Access to the drug was granted through what is known as compassionate use, a mechanism that allows patients with serious, debilitating, or life-threatening illnesses to receive experimental products in the absence of effective therapeutic alternatives.
Challenges in reaching the brain
One of the significant obstacles is the difficulty of getting the substance to reach the brain, given that the blood-brain barrier restricts the passage of many compounds. Furthermore, the siRNA must maintain its functionality after penetrating the cells. Clinical research specialist Daniel Dahis explained that 'it is not enough to reach the brain and enter the cell. Once inside, the molecule must still resist to remain functional. It falls into a kind of acidic bubble, which the cell itself uses to digest what enters it—and if it does not resist this environment, it is destroyed before taking effect.'
To help the siRNA cross the cell membrane, the technology incorporates a lipid chain known as C16.
There is no clinical study of ALN-6457 that allows for the evaluation of its effects in people. In previous experiments conducted on mice, a reduction of approximately 15% in messenger RNA linked to prion protein production was recorded, even at the lowest dose tested. This result demonstrates that the strategy managed to interfere with the mechanism, but it does not allow one to state that the disease will be halted, nor is there proof of clinical benefit or increased survival in humans.
So far, the findings indicate that it is a therapy that, in theory, reduces the production of the prion protein. Daniel Dahis, a clinical research specialist, considers this 'an indication that the strategy may be worth investigating, especially given a disease that currently has no treatment capable of stopping its progression. But this, of course, always considering safety uncertainties and an individual risk-benefit assessment.'
The most known data include that, in previous animal tests, no changes related to the substance were observed in neurological or organ evaluations. However, these studies were preliminary and short-term. Lito remains hospitalized in the ICU, and the next tests should help assess the impact of the application.
