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3 - Cystic fibrosis: the quest for a cure page 6
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3. The quest for a cure Link to the Medical Research Council web site

Figure 9. The three stages of the trials to treat cystic fibrosis with gene therapy.

Trial design
Read the passage below in which Duncan Geddes describes the UK trials. Highlight the main points and then answer the questions at the end.

The first human trials are designed to answer two basic questions:

We decided to begin with the nose, as its lining cells are similar to those of the lungs, and it is much more accessible for experiments. The first trial involved a single test dose to the nose. Following this, tests have moved to the lungs, first with one and then with repeated doses (see Figure 9).

CF volunteers make a number of sacrifices to help us with these experiments. They have to attend the hospital on numerous occasions and so give up a lot of time. They have measurements made from their nose and lungs, which can be uncomfortable. And they agree to having a biopsy of the inside of their nose or lungs, which involves taking a small specimen of cells under local anaesthetic. Naturally, not everyone is able to help!

Safety is assessed by questionnaire and clinical examination, as well as by microscopic examination of the biopsy specimens and long-term follow up. We judge the efficacy by measuring the electrical charge on the inside of the nose or the lungs and by estimating from biopsy specimens how well the gene has been incorporated into cells and how much of the product - the protein CFTR – is present. The trial is done under double-blind conditions so that neither the patient nor the researcher knows whether the gene transfer system or a placebo has been given.

The day-to-day running of the trial poses particular challenges as the researchers need to fit in with the volunteers' timetable. This often means working all hours, including evenings, weekends and holidays. Furthermore, any trial which uses measurements in the nose can be knocked off its stride by the common cold. This minor event has already severely disrupted our programme a number of times.

When we are all convinced that the system we are using is safe, we will go on to the next stage of the programme. Each stage has already been provisionally mapped out, but may need to be changed in the light of advances in the basic technology of gene transfer.

When trials are successful enough, we will move to full-scale production. In drug trials it is usual for a pharmaceutical company to look after all production issues, including the costs. In the UK, companies are reluctant to scale up production for gene therapy trials. In contrast, biotechnology companies are closely involved in American and French gene therapy research. While the UK independence has some advantages, a hospital/university-based research team lacks a drug company' s experience in formulation, production and regulatory issues as well as being at a financial disadvantage - a new drug may cost as much as £200 million to develop and take to the marketplace.

Question 4

a) What is a placebo?

b) Explain the importance of carrying out the trial under double-blind conditions.

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