Dominique Pezziardi from Merck Serono in Geneva particularly enjoys his job at present. "It's the most motivating challenge I've faced in my career," he explains. Pezziardi has been given responsibility for a so-called orphan disease, as rare conditions are known in the medical world. There are around 7,000 such diseases, 80 percent of them genetic. And although the symptoms are often serious, suitable treatments are in short supply.
According to the European definition, a disease is categorized as rare or "orphan" when, at most, five out of every 10,000 people suffer from it. Special incentives are in place to support the development of drugs for such conditions. Once approved, for example, these so-called “orphan drugs” enjoy various privileges for a certain period of time. All of these measures are designed to make it easier for innovative companies to develop drugs for small target groups.
In this research area, success is not measured in terms of volume— unlike the so-called blockbuster drugs, which generate huge sales. As the name implies, orphan diseases are largely unknown to the general public, andknowledge of them remains the domain of a few specialists. Likewise, the sufferers are often widely scattered and left alone with their condition. In recent years, however, their plight has attracted increasing interest, not merely among specialists like Pezziardi from the pharmaceutical industry but also patient groups, dedicated doctors, and public figures such as Eva Luise Köhler, wife of Germany's former Federal President, who is the patron of ACHSE, an alliance of patient associations for people with orphan diseases.
Rare diseases, but surprisingly many patients
Today ACHSE unites more than 90 self-help organizations for people living with orphan diseases. Saskia de Vries, the alliance's spokesperson, explains why there are more people with orphan diseases than might be expected: "If we realistically assume an average figure of 7,000 cases per orphan disease, this yields the astonishing result that four percent of the population suffer from one or another of these conditions! That translates into almost four million people in Germany, 30 million in Europe, and ten passengers on a randomly selected medium-sized aircraft.“ One of the prime aims of ACHSE is to raise awareness among the general public and healthcare professionals. At Berlin's Charité hospital, for example, the organization's very own specialist is on hand to assist fellow physicians with the diagnosis of rare conditions. Meanwhile, sufferers and their families are also increasingly active on the political level through bodies such as Eurordis, the European umbrella organization of patient advocacy associations for orphan diseases.
The end of April will mark the tenth anniversary of the implementation of EU legislation to promote the development of orphan drugs; such legislation has already been force in the U.S. since 1983. That has made it easier for the pharmaceutical industry to work in this field. As a result, the number of orphan drugs licensed in Europe has risen and now stands at around 50. Merck is also involved this process. This is where Dominique Pezziardi comes in, and it's soon clear why he is so satisfied with his job.
PKU — the first orphan disease discovered
The baby's foot is pricked and the dried blood is examined in the laboratory for rare metabolic disorders
Pezziardi has immersed himself in the study of a disease that occasioned some of the earliest work carried out in the field of orphan diseases. The pioneer in question was the Norwegian physician Ivar Asbjørn Følling, who was the first to discover, back in 1934, why some initially healthy babies suffer from progressive brain and nerve damage, leading to a drop in intelligence and in some cases to epileptic seizures and serious emotional disorders. Følling found the lead he was looking for in the children's urine, which, as he discovered, contained large amounts of the substance phenylpyruvate.
Phenylpyruvate is one of the so-called ketone bodies, which are otherwise only present in the body in such large amounts in the event of extreme metabolic states such as those resulting from sustained fasting. This discovery was the all-important first step toward understanding a disorder that can have grave consequences if it is left untreated. "If PKU is not detected right after birth and then treated, it impairs brain development," Pezziardi explains. "Newborn babies have therefore been routinely tested for many years now." And that's thanks to a procedure developed by the second pioneer in this field, U.S. microbiologist Robert Guthrie. Back in the 1960s, he developed a test that today is familiar to millions of new parents: a prick in the baby's foot that leaves a few drops of blood on a test card. If the lab finds evidence of this genetic disorder, which is still known as Følling's disease in Norway and phenylketonuria, or PKU, in the rest of the world, action can be immediately taken to prevent damage to the baby’s brain.