A clinical trial with individuals affected by transthyretin-related familial amyloidosis (ATTR) has shown that compound SOM0226 (tolcapone), discovered and patented by the biopharmaceutical SOM Biotech, based at the Barcelona Science park (PCB), is four times more effective than drugs currently available to treat this degenerative rare disease.

The test confirms the conclusions of the study on drug repositioning that was just published in Nature Communications by researchers at the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona (IBB-UAB), in collaboration with SOM Biotech, describing the potential of tolcapone.

ATTR is a minority and degenerative disease that mainly affects the nervous system and muscular tissue of the heart (myocardium) and is usually inherited from parents to offspring. It occurs when the liver and other parts of the body produce mutations of the protein transthyretin (TTR), which loses its functional structure. This causes formation of toxic aggregates of amyloid fibers deposited, depending on the mutation involved, in different organs such as the brain, kidney, nerves, the eye or the myocardium, causing their dysfunction and diverse variants of the disease.

In the published study, researchers have shown in biophysical assays, in vitro cell cultures, ex vivo in human plasma and in mice models of the disease that tolcapone is a potent inhibitor of the initiation of the process of aggregation of amyloid fibers by means of TTR, which acts by stabilizing protein structure, hence reducing the progression of the disease. This is so far an unknown property of this drug, which is already being used to treat Parkinson’s disease. The compound has been shown to be four times more effective than the only drug that is currently available to treat the polyneuropathic variant of the disease.

The results have been positive for all the studied variants of the disease: polyneuropathy and familial amyloid cardiomyopathy (which affects the peripheral nerves and myocardium, respectively) and senile systemic amyloidosis, sporadic form affecting a very high percentage of men over the age of 60 years (also affects the myocardium). Furthermore, it has been shown that it crosses the blood brain barrier, which would make it the first treatment for variants of the disease that affect the central nervous system.

According to researchers, the drug has the potential to become an effective molecule to prevent depositions of the protein that cause the disease and slow down its progression. The drug could be on the market within five years, as it has already been tested in a clinical trial ran on individuals affected with the neuropathic variant. In this trial -a proof of concept trial that evaluates the efficacy and safety of the compound-  conducted jointly by SOM Biotech and the Vall Hebron University Hospital, the compound has shown its ability to stabilize 100% of TTR present in the plasma of all patients treated with a high safety profile.

A repositioned drug

The research work has been headed jointly by Salvador Ventura, professor at the Department of Biochemistry and Molecular Biology at the UAB and researcher at IBB, and SOM Biotech, a biopharmaceutical company specializing in the repositioning of drugs, discoverer and proprietor of the patent for the use of tolcapone for ATTR.

Drug repositioning identifies the suitability of molecules already approved for a specific therapeutic indication -as in the case of tolcapone for the treatment of Parkinson- for a different condition, thereby accelerating development and patient access to new treatments.

This strategy also favors a lower treatment cost, which could make it possible, as in the case of tolcapone, the administration in countries like Brazil or Portugal, important foci of the polyneuropathic variant.

The drug has received the designation of orphan drug for ATTR by the US Food and Drug Administration (FDA), a relevant fact, taking into account that in the US  there is a large group of patients affected by the cardiomyopathic variant of the disease.