Abstract

CRM197: reduction of atherosclerotic stenoses in carotids of three elderly patients

Author(s): Silvio Buzzi, Giorgio Buzzi, Anna Maria Buzzi and Sauro Martini

Background: Many years ago, diphtheria toxin was shown to exert an antitumor effect in mice and humans. However, these old studies suggested that the molecule, expected to affect cancer with its toxicity only, could also act through an immunological mechanism. In recent years, this suggestion has been reappraised and crossreacting material (CRM)197 administered to advanced cancer patients has shown encouraging results. CRM197 is a nontoxic mutant of diphtheria toxin that cross-reacts immunologically with the native counterpart. Unexpectedly, a cancer patient treated with this molecule obtained, along with a small shrinkage of his lung tumor, a 27% reduction of an atherosclerotic stenosis of his internal right carotid. We were amazed at this result since we knew that the only drugs useful against atherosclerosis were statins.

Objective: This study aimed at investigating whether CRM197 may also affect atherosclerotic stenosis.

Patients & methods: Three elderly patients with moderate-to-severe carotid stenoses and a poor performance status consented to undergo an experimental treatment with CRM197. Patients were preliminarily examined for their immunocompetence against diphtheria toxin/CRM197. Two different doses were adopted: 1.7 mg/day for subjects lacking immunocompetence and 3.5 mg/day for subjects with immunocompetence. Treatment consisted of six subcutaneous injections of CRM197 administered in the abdominal wall on alternate days. A further dose (similar to the first) was administered six times, every 2 months. Side effects were unremarkable. The size of stenosis was evaluated periodically with careful ultrasound scan by the same operator.

Results: Surprisingly, even assuming that the ultrasound monitoring of the size of stenosis may be slightly inaccurate, all patients demonstrated a very slow but striking stenosis reduction. The mechanism accountable for these results could be immunological in nature.

Conclusion: Despite the fact that no firm conclusions can be drawn from this limited trial, the achieved results are undeniably very promising.