A.V.L.T.

Every so often health features appear in the newspapers; some papers publish specific health supplements, so citizens are to a greater or lesser extent informed of the current situation of various diseases and possible treatments.
There are however still lesser known situations and realities within the health field and we believe the problem of thalassaemia is among them. We therefore decided to interview the regional President of the Veneto Association for the Fight against Thalassaemia (AVLT), Dr. Elio Zago, to find out more about this disease that particularly affects our territory.

What is thalassaemia and how does it affect thalassaemia patients?
Thalassaemia is a hereditary disease of the blood. The red blood cells of thalassaemics lack a substance, adult haemoglobin, which transports oxygen from the lungs to tissues.
This deficiency is incompatible with life.
Consequently, thalassaemics must have on average two red cell transfusions every two weeks and have to undergo daily iron-chelating treatment administered through a hypodermic needle for an average of ten – twelve hours to remove the excess of iron that is deposited in the vital organs due to the blood transfusions. It is therefore a condition of great discomfort with a high risk of complications.

Is there any way to improve their quality of life?
There are two options: pharmacological research to develop a drug that can reduce the number of blood transfusions and consequently lead to a reduction of iron deposition, or gene therapy research to replace the faulty gene necessary for haemoglobin production with the healthy one.
The drug would greatly improve their daily life; substitutional gene therapy would provide a cure.

What is being done to develop the drug?
Two and a half years ago, in July 2000, following an Agreement between the Ferrara University Biotechnology Centre and the Rovigo “Associazione veneta per la lotta alla talassemia” (AVLT), a “Laboratory for research into pharmacological and pharmacogenomic treatment for thalassaemia” (Thal-Lab) was set up at the university. On the basis of this agreement, the AVLT decided to grant the Laboratory 500 million Italian lire for management costs during the first four years of activity. This was the beginning of a project that would of course need to be developed.

And have these developments been achieved?
The Thal-Lab immediately set itself two goals: to protect the research results by taking out patents and to establish relations with the pharmaceutical industry, without which there is clearly no possibility of developing new drugs. Both goals have been achieved: the Laboratory currently possesses six patents, three of which are international. Two of the international patents are co-owned by Chiesi Farmaceutici in Parma and negotiations are underway with other pharmaceutical companies for the others.
Moreover, the Thal-Lab has set up important international relations. Firstly with Prof. Eitan Fibach, a world-renowned scientist who works at JerusalemUniversity and subsequently with Prof. Pier Luigi Luisi, who is heading some extremely interesting research into thalassaemia at ZurichUniversity.

What are the prospects for gene therapy?
The most advanced research centre is in New York and is based mainly on the work of Prof. Michel Sadelain at the MemorialSloan-KetteringCancerCenter, and the Italian researcher Dr. Stefano Rivella, who heads a Gene Therapy Laboratory at CornellUniversity.
These two researchers published two research papers that have opened up new prospects for gene therapy research: the first appeared in the journal “Nature” in July 2000 and the second in “Blood” last December.
At the beginning of last October, Thal-Lab and AVLT signed an Agreement with Dr. Rivella which has enabled a researcher from FerraraUniversity to go and work in his Laboratory in New York.
We are convinced that this pathway offers great hope of success and we are therefore also financially committed to this line of treatment.

What has the Association’s overall role been?
The AVLT was highly committed to the idea of the Laboratory and has subsequently played a decisive role in its development and international dimension.
The financial commitment means that today we can grant five scholarships, two of which are financed entirely by us (in Ferrara and Jerusalem) and three wich are co-financed (in Ferrara, New York and Zurich), purchase equipment and materials for the Laboratory researchers, as well as covering other expenses such as patenting, and so on.
However, as important and decisive as the decision to create the Laboratory was, setting up a network that has enabled communications between numerous important figures in the scientific world has been ever more important. Each of them was already working prior to the creation of the Laboratory but individually, developing their own personal research area, publishing their own results and quite rightly advancing their own academic careers. Now, without having to give up anything they were doing before, those scientists have signed collaboration agreements, are working together in harmony, are exchanging information; in short, they are working as a group, participating in the creation of a well-organised, coherent project. I believe it is only right to underline the work the Association does daily to create these collective working conditions.

Does the Association have any other goals?
The AVLT believes that if the results of the pharmacological and genetic research one day live up to expectations, human clinical trials must also be conducted in Italy. The Thal-Lab and Dr. Rivella’s gene therapy laboratory must therefore reach an agreement with an Italian clinic. Over the last few months the Association has been in contact with an Italian clinic of great distinction and we hope that an Agreement will soon be signed.
This Agreement could “square the circle” since it would mean that all the fronts would be manned: pharmacological research in Ferrara, gene therapy in New York and clinical trials in another Italian city.

You are about to launch a new campaign to raise funds. Why?
As I mentioned, when the Thal-Lab was launched, the Association committed itself to providing finances of 258,228 euro for the first four years of activity.
The recent involvement in the field of gene therapy research means that substantial financial resources also need to be channelled in this new direction.
The AVLT therefore needs to have sufficient funds available to meet the needs of these commitments over the years.
Our “Campaign” will unfold over the first six months of 2003, so that the people who help us can choose the most suitable fund-raising days and the AVLT members can be present when needed.

Whose support are you seeking?
Naturally, from all the citizens of the Polesine. Thalassaemia is a problem that affects the Polesine in particular. A thalassaemic child can be born when both parents have microcythemia and in Polesine 7.5% of the population is microcythemic.
There is therefore an extremely high risk of new births. It is true that the Rovigo Hospital Microcythemia Centre and the AVLT are trying to counter this risk by providing citizens with information, but we should never lower our guard.
We are also seeking the support of blood donor organisations. The AVLT is a small Association whose members are almost exclusively thalassaemia patients and their families. We would be able to do little, certainly not enough, if for years we hadn’t had generous help from the local AVIS Blood Donor Groups.
We also ask for indirect help from parish priests to allow AVIS and AVLT volunteers to set up stalls in front of the churches.

How do you keep people informed of your activities?
The Thal-Lab has been on the Internet for a year now at the site: www.talassemiaricerca.unife.it
It is basically divided into two sections: the first, more technical one, provides information on the nature of the disease and on gene and pharmacological therapies, makes available the abstracts from publications on research and provides all the bibliographical references to the disease; the second section talks about the Association and provides news on its organisation, the financed research projects, fund-raising, etc.,

The AVLT believes it is important to underline the worldwide value of the research being carried out in Ferrara. Can you explain why?
There are hundreds of thousands of people all over the world today who suffer from thalassaemia. They mainly live in the area extending from North Africa to the Far East. In these countries thalassemia represents a serious health and social problem.
If the Ferrara Laboratory should one day produce the molecule capable of allowing the development of a new drug that can reduce or eliminate blood transfusions, with a consequent clinical improvement thanks to a normal absorption of iron in the organism, we would be witnessing a therapeutic event of extraordinary worldwide significance.
The Thal-Lab is not therefore working solely towards improving the health of Italian patients but all the thalassemics on the planet, and the marketing of a new drug in the above-mentioned countries would signify solving a serious problem that they are not currently able to cope with adequately.
We are therefore counting on informing those countries as soon as possible of the Ferrara Laboratory. We are already working on it by preparing an English version of our website. If those countries become aware of the important role of the Thal-Lab in the future of the fight against thalassaemia in their lands, we believe it won’t be difficult to obtain financial support for the Laboratory’s activities from their governments.
This might mean a lighter financial burden for the AVLT and consequently less need to turn to the help of our traditional generous supporters.

(translation by Ms Mary Hawkes)