The first hepatic transplantation (HT) performed in order to treat FAP was done in Sweden in 1990. In Brazil, it was firstly performed in São Paulo, in 1993; and, in Rio de Janeiro, in 1997.
As we will discuss later, the FAP is caused by deposits of a protein called transthyretin (TTR) when mutated. Ninety percent of the total TTR is produced in the liver. The hepatic cells of the mutation carrier are genetically determined to produce the mutated TTR protein, which may form amyloid deposits in different tissues and cause injury. However, no injury is observed in the liver itself, whose functions remain normal.
The aim of the liver transplantation is to prevent the production of mutated TTR. It is expected that there is no progression of the disease, as it allows replacing the main protein body producer. It is not a curative treatment of injuries that existed prior to transplantation. However, it is a highly invasive method, which forces the patient to make use of immunosuppressants and to the risks of a surgery of this magnitude.
Use of drugs that inhibit the aggregation of TTR: they are still under research and are not yet routinely used.
Newdrugsact stabilizing the Val30Met mutatedTTRprotein, thus preventing its amyloid aggregationin the tissues, which causes the injury. It is also expectednodisease progression.
One of these drugs, Tafamidis, proved to be effective in preventing disease progression, and is in clinical trial extension phase, waiting for marketing approval. CEPARM participates in this clinical trial (FX005 and FX006).
Anotherdrug, Diflunisal, is still being tested in clinical trials andthere are no studiesinBrazil. Itwouldalso act stabilizing themutated TTRprotein, preventing loss ofits normalstructure as well as its misfoldingin unitsthat could later form amyloid depositsin the tissues.
Future expectation: use of gene therapy in order to “correct” the production of TTR. It is still in pre-clinical testing in animals.
It is important that every patient who is suspected or known to be a carrier of a TTR mutation has access to genetic counseling, which is done in the center, in order to know the risk of passing it on to to their offspring, as well as other aspects involved.
There are other clinical trials taking place in the world in order to evaluate different interventions for treating FAP. At present, we are watching closely its development and actively participating in its adoption by the competent bodies in Brazil, namely: CONEP and ANVISA. These phase III studies will test the effectiveness and monitor side effects of two new drugs in patients with FAP and are expected to start in CEPARM in the second semester of 2014.
Tests with RNA interference
There is a worldwide study being conducted with patients with FAP, including Brazilian, which aims to inhibit the production of the mutated TTR by the liver. Two companies are involved in this trial is the one and the other Alnylan Isis. More details of this study can be seen in the links below.