What immune cells reveal about sleep disorders

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Daniela Latorre conducts research at the Institute for Research in Biomedicine.

Daniela Latorre conducts research at the Institute for Research in Biomedicine. (Photograph: Stefan Weiss / ETH Zurich)

Daniela Latorre wanted to be a scientist since she was a child. At the Institute for Research in Biomedicine, affiliated to the USI in Bellinzona and the Institute of Microbiology, she is finding evidence that narcolepsy is an autoimmune disease. She has now received the Pfizer Prize for Research 2020 for her pioneering work.

"This is my very first interview," Daniela Latorre explains with a smile at the start of the conversation. It probably will not be her last: the young researcher from Italy has made a name for herself in recent years with her studies on narcolepsy. As an SNSF PRIMA group leader at the Institute of Microbiology at ETH Zurich, she investigates the autoimmune basis of neurological disorders.

She has received numerous awards for her work on narcolepsy - at the tender age of 35. After winning the Young Scientist Award from the European Narcolepsy Network in 2019, she has now received the Pfizer Prize for Research 2020. "It’s a wonderful feeling. All these awards recognise the work my colleagues and I have put into our research," says Latorre.

Is narcolepsy an autoimmune disease?

Narcolepsy is a chronic sleep-wake cycle disorder triggered by a loss of neurons in the lateral hypothalamus. As a result, the brain produces only low levels of the neuropeptide hypocretin, which is responsible for the sleep-wake rhythm. The illness affects 1 in every 2,000 people.

There is a major gap in this research area that the young researcher wants to close with her work. "Our results will improve awareness of what’s behind this illness," says Latorre. She wants to get to the bottom of the causes of the disease. "The symptoms may be treatable, but there’s no cure," she notes. In her current and so far largest research project, she investigates autoimmune factors that may lead to this illness. It is thought that narcolepsy may be an autoimmune disease, and Latorre has been able to show that this is very likely the case.

The research is anything but easy: "It’s extremely difficult to do research in this field. You have to use sensitive and precise measurement methods in order to be able to detect and isolate rare self-reactive immune cells in the blood and cerebrospinal fluid," she says. If the immune system malfunctions, an excess of these cells is produced; they then damage the neurons in the hypothalamus and interfere with the production of hypocretin, leading to narcolepsy.

Although the research is intricate, Latorre nevertheless succeeded in isolating and characterising autoreactive T cells targeting neuronal antigens in narcolepsy patients. This work was done under the supervision of Federica Sallusto, Professor of Medical Immunology at ETH Zurich, and Professor Claudio Bassetti from the university hospital Inselspital Bern. Together with her colleagues, Latorre was able to demonstrate for the first time that autoreactive T lymphocytes are found in the immune system of patients with narcolepsy. "This is clear evidence that narcolepsy is an autoimmune disease," explains the Italian.

The path to the clinic

It was Sallusto lab’s research collaborator Professor Bassetti who made the team aware of narcolepsy during the time Daniela worked as a postdoc at the Institute for Research in Biomedicine in Bellinzona. That’s when the cooperation between Sallusto lab’s team and Inselspital Bern began. "Doctors need help from researchers to answer practical questions," says Latorre. Thanks to the research findings, clinical specialists can better understand the mechanisms underlying sleep disorders and develop effective treatment methods. "It’s too early-stage to be able to treat patients yet. But we’re working hard on it," she says.

Latorre and her team process the blood once they get blood samples from patients. (Photograph: Stefan Weiss / ETH Zurich) Later they are going to study the samples in their vitro assays. (Photograph: Stefan Weiss / ETH Zurich) Blood is placed on top of the Ficoll-Hypaque solution. (Photograph: Stefan Weiss / ETH Zurich) After centrifugation, the immune cells of interest will form a ring lying just on top of the Ficoll solution. (Photograph: Stefan Weiss / ETH Zurich) Daniela Latorre is imaging cultured cells under a Fluorescence microscope. (Photograph: Stefan Weiss / ETH Zurich) The Italian scientist is analysing cultured cells under an optical microscope. (Photograph: Stefan Weiss / ETH Zurich)

Putting the puzzle together

Latorre grew up in a small town in southern Italy, the daughter of a homemaker and a factory worker. Although her family had little connection to science, she found her way to it early on. Her strongest driver was her irrepressible curiosity: she wanted to know what was behind things. "Even as a child, I was fascinated by how our body functions and what mechanisms lie behind it. How all these tiny parts - starting with DNA, then cells, then organs - work together and function independently. It’s fascinating," she says. She loves putting the whole puzzle together piece by piece through new findings from research. If she finds a "bug", as she calls it, she wants to find a way and means to fix it.

To her, it’s obvious: she didn’t find science, it found her. "I can still remember vividly how I wrote a letter to ’Babbo Natale’, the Italian Santa Claus, when I was eight years old asking for a microscope," Latorre relates. Enchanted as she was by scientific processes, her secondary school teacher recognised her talent. It was this teacher who recommended that she study biotechnology in Rome. She was the first in her family to take an academic path. "My family is very proud of me and supports me in my research career in every respect," the young researcher adds.

There’s still much further to go

Latorre will devote herself to narcolepsy for a long time to come. "This is only the beginning. The journey will be much, much longer," she says. Early diagnosis and clinical treatment methods based on her research still need to take concrete form. The way from the initial research concept to a finished treatment method is lengthy, but Latorre is not deterred: "If we’re able to successfully treat patients thanks to our research, that would be the crowning moment for me."

Angelika Bühler