Callerio Foundation

Linfa

Plain language articles


In other hands NAMI-A would never have been born

In the middle eighties the scientific world still believed that the perfect anti-tumour drug had to show a strong cytotoxicity for tumour cells. In 1989, when we decided to study the anti-tumour properties of a new series of ruthenium compounds, this belief was still strong and continued to be the guideline for basic studies. Because of this the pharmaceutical company which forced and supported the initial study on this series of ruthenium compounds, within a few years would doubtlessly stop supporting these compounds which did not meet the minimal toxicity requirement for an anticancer agent.
In fact, NAMI-A belongs to a class of ruthenium compounds which were synthesised with the hope of obtaining a strong selectivity for the mass of a solid tumour - in other words, it should have been toxic for tumours but not for the surrounding healthy tissues (unlike almost all anticancer drugs). In order to do that, the active and toxic aspects of NAMI-A had to be activated by the tumour cells themselves, and would therefore work only within the tumour mass.

To make a long story short, we may say that this was not the case of NAMI-A. It showed only a poor activity against the experimental tumours used in laboratory. However it was far from ineffective: NAMI-A showed instead a surprisingly strong ability of killing the metastases that these tumours used to form in distant sites. We had the chance to remark this effect because we had acquired a long experience on the pharmacological treatment of metastases since the mid-seventies.
However — no money, no research. No matter that metastases represent the ultimate goal of cancer chemotherapy — no cytotoxicity, no further grant support.

Today many people appreciate the innovative characteristics of NAMI-A, which recently entered phase 1 clinical trials - that is, the first study on humans, necessary to evaluate the maximum dose which can be administered to a human being. However it shall be remembered that the so called "institutional funding" refused any support to the studies that investigated on the pharmacological behaviour of NAMI-A.

Probably times were not ready as yet. Some said that they wouldn't finance studies on new drugs, surely not ones which would require experiments on mice. Others found these studies not innovative enough as to deserve their intervention, both in Italy and in Bruxelles. So - sad as it is telling it - we had to work on our own resources for over 4 years, until eventually some people saw it worthwhile to sustain NAMI-A development because of the great advantages that people might have from this drug – but this is just very recent story.

By the way, NAMI is the acronym for New Anti-tumour Metastasis Inhibitor; -A means that this is the first of a series.

Gianni Sava
(also in the name of all people who accepted this challenge,
including the students who prepared their theses on the subject)


Why lysozyme should deserve a better medical interest

Lysozyme was as appreciated by Alexander Fleming, the Nobel Prize who discovered it, to the point of trust in it more than in penicillin. The reality then revealed quite different: today everybody knows what penicillin is, but only a few recognise the word "lysozyme". Why? That's obvious! Penicillin has been the leading compounds upon which bacteria chemotherapy grew, whereas lysozyme did not generate any school whatsoever: the blatant, explosive success of early antibiotics "stole the scene" to anything else.

But let’s forget for a while this extremely important aspect of penicillin and let’s freely analyse the biological characteristics of lysozyme.
Lysozyme is only a generalisation: under this word at least 80 different compounds might be listed. You are kindly invited to have a look at the book published by Pierre Jollés a couple of years ago. Leaving alone the intrinsic beauty of some treaties - much better appreciable anyway if you are a chemist or an immunologist - there are few considerations that might be made intelligible to everybody. Lysozyme might have a medical value, but this value is not immediately appreciable for it is not used widely enough to prove it in an unobjectionable way. It looses a considerable share of its potentialility when used intravenously: it is a protein, and as such it may cause the obvious damage that any protein administered intravenously causes: anaphylaxis. But it can be used orally as well, or in any other form that avoid its direct introduction into the bloodstream. Interesting works by Russian researchers show how it may control infections of the upper digestive tract when used as a chewing gum, and other studies demonstrated that also many bacterial infections in children, remarkably the ones that cause dysentery, are better treated by a combination of lysozyme and an appropriate low-dose chemotherapy.

Another important aspect concerns the effects of the orally administered lysozyme on the immune system. Apart of the many laboratory studies whose comprehension can be hard to digest even to the expert, when used in humans it provides benefits clearly ascribable to its effects on the immune system. For instance, in a study aimed at ascertaining the capacity of lysozyme to enhance patient's recovery from immune depression caused by cancer and anti-cancer therapies, aside of causing a remarkable normalisation of white blood cells, it shown an unexpected activity against several infections typical of the cold season.
Certainly hen egg-white lysozyme is not as noble as a modern biotechnological product, however in a period in which the so called "soft" therapies are even more appreciated, it deserves a better attention than it presently has.

I was forgetting the most important aspect. Right after the last world war, an estimator of Alexander Fleming, who also happened to co-operate with him, made available lysozyme on wide scale by extracting it from hen egg-whites. This procedure allowed a Pharmaceutical Company to grow, lysozyme to be widely used in medicine and food manufacturing, and Carlo Callerio, the estimator of sir Alexander Fleming, to build up the Foundation which carries his name and still promotes the studies on lysozyme.

Gianni Sava
(whose pen was guided from Heaven by
his magister and friend Carlo Callerio)