The Vall d'Hebron Barcelona Hospital Campus and the Hospital Clínic of Barcelona have participated in an international study that demonstrates the efficacy of a new pharmacological treatment for transthyretin amyloidosis, the most common form of familial amyloidosis. Josep M. Campistol, nephrologist and CEO at Hospital Clínic, and Josep Gámez, neurologist at the Vall d'Hebron Barcelona Hospital Campus, are co-authors of the study published in the https://www.nejm.org/ New England Journal of Medicine (NEJM).Hereditary transthyretin amyloidosis (TTR) is the most common form of familial amyloidosis. It is a rare systemic disease caused by mutations in the gene encoding for transthyretin (a protein) and affects about 50,000 people worldwide. The average life expectancy, untreated, from symptom onset is 3 to 15 years, and the presence of cardiomyopathies is associated with a worse prognosis.The liver is the main source of the TTR protein and, in this type of amyloidosis, both normal and altered protein accumulate in the form of deposits of amyloid substance in peripheral nerves, heart, kidney and gastrointestinal tract. Thus, different forms of the disease appear, such as polyneuropathy (involvement of the brain) or cardiomyopathy (involvement of the myocardium). "Until now, current treatment options included liver transplantation or the use of drugs to stabilize the circulating protein and thus prevent the formation of deposits, but in many patients the disease continues to progress," explains Josep. M. Campistol.A new pharmacological treatment to reduce TTR in bloodIn the study published in NEJM researchers evaluated the efficacy and safety of Inotersen, a second generation antisense oligonucleotide (ASO) inhibitor. It is a drug that inhibits the production of TTR in the liver by binding to the TTR microRNA and reducing the production of both normal and pathological TTR protein. It is easily to administer subcutaneously once a week. Due to the half-life of the drug, Inotersen provides a constant reduction of TTR over time.A total of 172 patients with hereditary transthyretin amyloidosis with polyneuropathy, in the presence or absence of cardiac involvement, have participated in this international phase III study. The results show that treatment improves the neurological disease and the quality of life of the participants, regardless of the disease stage or the presence of cardiomyopathy. Thrombocytopenia (decrease in platelet count) and glomerulonephritis (inflammation the glomeruli, the small filters in the kidney), which appeared in 3% of patients in each case, were the most frequent adverse events and were managed with enhanced monitoring."Inotersen is a gene therapy that allows subcutaneous administration of oligonucleotides that favor the degradation of the TTR protein microRNA, thus reducing TTR liver production," explains Josep Gàmez, who is also coordinator at Vall d'Hebron of the CSUR in Rare Neuromuscular Diseases and the European Reference Network on Neuromuscular Diseases (EURO ERN-NMD).