Rare diseases: “What is not known, cannot be diagnosed”

The internist Julin Fernndez Martn explains the importance of an accurate diagnosis for an increasingly personalized medicine in these pathologies, and gives as an example the field of those of autoinflammatory origin, in which he investigates

Patient-centered medicine and personalized treatments have revolutionized areas such as cancer, infectious diseases and rare diseases. All of them”they mutually enrich each other with the research carried out in each field. But, at the same time, there is nothing more frustrating than telling a patient that we don’t know what he has.something that happens more and more frequently because there is more and more knowledge about the link between one and the other”, explains Dr. Research Galicia Sur de Vigo.

A recent report by the NGO Rare-X highlights the importance of listing all rare diseases. Traditional estimates considered that there were around 7,000 rare diseases, but the works precisely establish that there are 10,867.. For Fernndez Martn, it is essential to enumerate and define them because, as he points out, “what is not known is not diagnosed”.

“Physicians who are dedicated to patients with rare diseases accompany the patient, for better or for worse, throughout their life. And, when you diagnose one, you not only diagnose the patient, but also all his relatives, who suffer with him from his disease. There is a myth that many patients don’t have treatment, but everyone does. Maybe not specific, but things like nutrition, psychological support or physiotherapy help. What there are not are specific resources to complete everything that this type of patient needs, ”he specifies.

fix the genes

But how do you investigate a rare disease? Fernndez Martn’s work focuses on diseases of autoinflammatory originin which the failure of a single gene disrupts the body’s defense mechanisms, both against infections and against the development of tumours.

The hopes of patients and researchers are pinned on gene therapy and other approaches, which could replace and repair the faulty gene.

The scarcity of patients makes this work difficult, but there are several approved gene therapies and, from his point of view, “they are not yet the present in all diseases, but they are the immediate future”.

Amyloidosis is a large group of autoinflammatory diseases that arise because up to 35 different proteins are deposited in different organs of the body. Three types of amyloidosis are responsible for 80% of cases of the disease: AA amyloidosis, which is associated with inflammation; AL, which is associated with blood tumors, and transthyretin protein deposition amyloidosis, which are hereditary.

“The three have a specific treatment. For this reason, the investment to specifically identify the protein involved and give the typed patient the appropriate drug is so important.. The case of transthyretin amyloidosis is particularly interesting: the treatments are used with an RNA technique, similar to that used in the development of vaccines against the coronavirus. In this case, the synthesis of the pathogenic protein is inhibited”, he underlines.

A thousand faces of a disease

Dr Fernandez Martin also has Fabry disease as one of the focuses of his research. This is another inherited metabolic disease caused by the malfunction of a single gene that codes for a protein found in the cell membrane that protects us from frequent bacterial infections.

“There are more than a thousand variants described of Fabry disease, its diagnosis is therefore extremely complex. This difficulty is linked to the current concept of precision in the definition of rare diseases: a common nomenclature must be used, classifying the person with their signs and symptoms. This is particularly important in these diseases, because the precise terms are included in the databases so that the artificial intelligence classifies and analyzes the patients appropriately,” he describes.

“However”, he concludes, “although it is a difficult disease to diagnose and manage patients, there are different projects to treat it with gene therapy”, some developed by Dr. Fernndez Martin himself. “For now, current treatment is based on three approaches. In the first, the missing protein is identified, manufactured in the laboratory and infused into the patient every 15 days. It is useful for all types of disease, but the patient depends on having a hospital nearby throughout his life. The second treatment is oral, with very effective drugs called chaperones, but they only work in 25-30% of patients. Finally, there are drugs that reduce the toxic substrates produced by the disease, although their results are modest.