Professor led French research foursome on the trail of rare brain disorder

‘I love to challenge dogma, and all four of us actually feel the same,’ says neurology professor and neuropsychiatrist Marie-Germaine Bousser, the Grand Old Lady of the research foursome receiving the 2019 Brain Prize.

The prize is recognition of more than 30 years of eminent scientific teamwork to map the hereditary disorder CADASIL, which causes strokes in the small vessels in the brain and frequently also leads to dementia and premature death.

Marie-Germaine Bousser talks of challenging dogma with a slightly ironic smile. It’s not the challenge itself that she values. She operates on a different logic – as a researcher, you have to challenge dogma if you want to replace commonly held, imprecise perceptions with precise, evidence-based knowledge. And it goes without saying that this knowledge needs to be useful.

Professor Bousser is today 75, but when she examined ‘Mr C’ in 1976, as a young neurologist, this was exactly what she set to work on – without knowing it at the time. Mr C was a middle-aged man with symptoms which were confusing to say the least:

He had had several small strokes, he suffered from migraine and he was in the late stages of dementia. However, on closer examination, his disease presentation did not seem to match any known diagnosis. Professor Bousser explains:

‘The head of the neurological department at Pitié-Salpêtrière Hospital, where I was working at the time, thought it could be Binswanger’s disease – but without the blood pressure elevation that characterises Binswanger’s. I rejected that idea out of hand – and I wouldn’t budge – because I was sure it had to be something else.’

And, a few years later, it became crystal clear that Professor Bousser was right. It was definitely not Binswanger’s disease, which is another condition characterised by strokes in the cerebral small vessels.

In 1985 Mr C’s children visited her clinic, and their symptoms were precisely the same as those originally presented by their father.

Long-term collaboration
Marie-Germaine Bousser, who is today professor emerita at Lariboisière Hospital in Paris, has received a great many congratulatory messages since the Lundbeck Foundation announced on 5 March that she and her colleagues, Anne Joutel, Elisabeth Tournier-Lasserve and Hugues Chabriat, are this year’s Brain Prize winners.

The prize has attracted international attention, simply because it is the world’s largest brain research prize: in addition to the honour, prizewinners share equally a monetary award worth 1 million euros. As far as the 2019 winners are concerned, this honour is a reward for decades of unremitting collaboration, and Marie-Germaine Bousser puts this into words here.

Before the interview, she was asked a question, which was, in essence, about sustaining momentum: how do four scientists actually keep up their enthusiasm for 30 years? This was a question she liked, because it gave her the opportunity to reflect, and she replied:

‘As I see it, the main point is that all four of us are doctors, we’ve all had patients with CADASIL – and we’re all extremely aware that this is a very distressing disease. On top of this, we like working hard, we’re inquisitive, we have great professional respect for each other, we trust each other – and we’re able to control our egos! And then, as I’ve already mentioned, there’s the question of dogma – which we all very much enjoy challenging and questioning.’

‘A horrible name’
The other members of the foursome are, today, 54 (Joutel), 55 (Chabriat) and 64 (Tournier-Lasserve). So, they were all pretty young when Professor Bousser involved them – one by one – in her work to explain the mysterious disorder which would later be named CADASIL.

If CADASIL sounds a little technical, it could be because it is actually an acronym of the full name of the disease, which in itself is a tongue-twister: ‘Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy’.

Marie-Germaine Bousser constructed the acronym in the 1990s when the research foursome had defined so many aspects of the disease – including the genetics, elucidated by Professor Lasserve – that they had an article accepted by Nature, one of the world’s most prestigious scientific journals.

It was important that the acronym could be pronounced in English, and from that point of view it works well. However, it is a different matter altogether for French-speakers. Marie-Germaine Bousser explains that, in French, the three syllables, CA-DA-SIL, sound a little like ‘a case that belongs in a mental hospital’:

‘At one point, I got a call from a member of one of the families affected by CADASIL. They asked why I on earth I’d chosen such a horrible name for the disease. I could only apologise and say that I’d never thought along those lines. I’ve since considered what else it should be called, but it’s too late to change anything now – the disorder is known internationally as CADASIL.’

When they began, the four prizewinners found it difficult to obtain funding for CADASIL research, partly because the disease had only been observed in one French family at that point. ‘Today, CADASIL has been identified in several hundred families in France alone, which makes it easier to get our hands on research funds. For instance, Hugue Chabriat and Anne Joutel have recently received a major grant from the French state,’ says Professor Bousser.

Although she has now retired from day-to-day CADASIL research, her commitment to scientific issues has not waned. Among other things, she is a member of the Comité Consultatif National d’Ethique, the French equivalent of the Danish Council on Ethics.