There is currently a FAP clinical trial recruiting patients at Tel Aviv

 Medical Center. The following is written by the Principal Investigator, Dr. Kariv.   

Immediate objective: To establish the ability of erythromycin  to enable synthesis of normal protein in patients with nonsense mutation in the Adenomatous polyposis coli (APC) gene using both in-vitro models and patients with familial adenomatous polyposis (FAP).

The role of APC in preventing cancer lies in its ability to control the nuclear levels of b-catenin.   Almost all (95%) APC mutations in colorectal cancer (CRC) are mutations called nonsense or frameshift that result in a truncated, unfunctional APC protein.

Our preliminary results indicate that erythromycin can indeed lead to APC nonsense mutation read through, which means that the antibiotic binds the ribosome (the organelle in the cell in which protein synthesis is taken place) and cancels the order given by the abnormal mutation to stop the synthesis of the protein. We have data proving this concept in cell culture and in mice, some of it has been published (gut 2010).

In this research we suggest to use our preclinical proof-of concept studies and move on into practical studies using erythromycin to induce read through of APC mutations in FAP patients aiming at decreasing their disease symptoms with the long term goal of treating all CRC patients harboring nonsense mutations in the APC gene.  

A subpopulation of this study will be FAP patients with existing polyps of the upper and lower gastrointestinal tract and patients with desmoid tumors. We expect to recruit around 7-10 patients from 8 families. Patients will be treated with 500mg erythromycin twice a day for a period of 16 weeks. Endoscopic and histological response will be tested by upper and lower endoscopies at baseline and after 8 and 16-20 weeks of treatment. Desmoid size will be evaluated at baseline and after 16 weeks of therapy by CT/MRI imaging. Tissue samples will be collected at baseline and after 8 and 16 weeks of treatment. We will examine the levels of APC, beta-catenin and Wnt target genes in frozen polyp tissue samples before and after treatment in relevant cases. We will also look at stem cells markers, before and after treatment. In FAP patients with desmoid tumors we will evaluate by standard imaging methods the size of the desmoid tumors before and after treatment. We will compare the clinical response for polyp size and number to the in vitro data fro relevant patients. The erythromycin treatment will be given in addition to any chemoprevention the patient already receives.