AWARD. This year’s Minor Fernström Prize at Sahlgrenska Academy goes to Elisabet Jerlhag Holm, Associate Professor in Pharmacology. She conducts research on what happens in the brain when we develop ad addiction to alcohol and other drugs, with the goal of identifying new medications that can treat patients with dependences.
Elisabet Jerlhag Holm has done pioneering studies on neurobiological mechanisms for diseases of dependence by investigating various appetite-regulating hormones and their effects on the brain’s reward system, and how they affect the intake of alcohol and drugs. The team was first in the world to show that if the appetite-reducing hormone glucagon-like peptide-1 (GLP-1) is added, alcohol is perceived as less rewarding and alcohol consumption in mice decreases.
“Of course, it’s a great honour to receive this prize. Above all, it’s very enjoyable that others outside our own team recognise what we are doing as important and interesting,” says Elisabet Jerlhag Holm.
This is not the first time that Sahlgrenska Academy’s prize committee is choosing to highlight the GLP-1 research domain. Last year’s prize winner, Karolina Skibicka, also conducts research on GLP-1, but with a focus on food intake.
Changes in the brain
Alcohol addiction is just as common as depression, but antidepressants are nonetheless prescribed 50 times more often than the handful of medications available for alcohol addiction today.
“Unfortunately, alcohol addiction is still seen as more of character flaw than the neuropsychiatric disease that the condition actually is. This is despite the fact that it’s known that the brain is altered in individuals who suffer from an addiction. There are a number of studies showing that there is an inbalance in the brain reward systems in patients with addiction. It has been demonstrated for example, individuals with alcohol dependence display fewer dopamine receptors in the ventral striatum, an area of the brain linked to reward as well as dependence,” says Elisabet.
New medications are needed to the large percentage of patients who do not get help from the medications approved today for the treatment of alcohol addiction. Elisabet Jerlhag Holm believes the poor response to today’s medications is because the underlying causes for people becoming dependent on alcohol vary:
“Some drink to dampen anxiety, others to experience euphoria and stimulation, and yet others drink for entirely different reasons. Whatever the case may be, we know that both genes and environment are involved in development of addiction.”
Given that there are so many different factors that regulate dependence, Elisabet also does not believe that one single medication will help everyone:
“Instead, we need several medications against dependence to be able to offer patients treatments that are as individualised as possible in the future, where the cause of the disease determines what medicine is chosen. This combined with some form of social psychology support treatment, I believe will be important parts of future addiction care.”
The team she leads consists of one postdoc, one technician and three doctoral students. Right now, they are in an exciting phase as their multiyear experimental research is on the way to being put to use in the clinic. In cooperation with Professor Bo Söderpalm, who is a Senior Physician at the addiction clinic at Sahlgrenska University Hospital, they are now in the midst of planning the first clinical study based on their preclinical research results.
“Planning a clinical study is a challenge since it’s so new to me, but the possibility to learn new things is also one of the most appealing things with research. It’s a researcher’s privilege to be able to guide your projects in the direction you’re personally interested in and teherby get the chance to learn more about,” says Elisabet, who cannot provide more details about the study.
Nowadays, she is rarely in the lab, she is instead focusing on coaching the junior researchers in the team as well as on bringing in new research funding to the team. Planning and structuring the experiments can also result in odd tasks – in an area in the corridor the new walls for cages for a behavioural experiment the team is planning can be found. Elisabet spent part of her summer painting in the correct, black-and-white pattern.
Ten years since earning her PhD
It is largely a coincidence that she is conducting research on dependence. As a student at the university’s bioscience pharmaceutical programme, she was already fascinated by the complexity of the brain and the fact that there is so much we do not know about the brain. In her synchronized skating team at the time, there was also a skater who was a doctoral student in a research team at the University of Gothenburg who was researching addiction. Through him, she came into contact with Jörgen Engel, who eventually became Elisabet’s supervisor, and who is still a mentor in the research team:
“It’s interesting to be able to discuss with somebody like Jörgen, who was involved since the beginning. He was there when dopamine was identified to be important for addiction and can he provide interesting insights, often with a historical perspective,” says Elisabet.
It was also Jörgen who became interested in the connection that appeared to exist between appetite control and dependence. In studies done at a population level, it was observed that alcohol addiction was more common in the families where binge eating. This became the focus for Elisabet’s thesis, which she defended in 2007. In the thesis, Elisabet showed that the hormone ghrelin, which until then was only thought to be significant to our appetite, also activates the reward system. In continued studies, the research team showed for the first time that alcohol is perceived as less rewarding and that mice consume less alcohol if the effects of the appetite stimulating hormone ghrelin are blocked.
Leading research teams
She has since expanded her research focus to comprise more appetite-regulating hormones as well as more diseases of dependence – not just alcohol and other drugs, but also behavioural addiction, such as sex. Besides ghrelin and GLP-1, the research team was also the first to show that the appetite-reducing substances neuromedin U and amylin are linked to the perception of alcohol – activation of these receptors cause a reduced euphoric effect of alcohol as well as a decrease in the consumption of alcohol.
“Research is incredibly enjoyable and I am thankful for every day that I get to delve into the various projects. It’s a luxury to allow creativity and curiosity guide where the projects go,” confirms Elisabet.
The research team also followed up these intial preclinical data with studies of human genes, where they showed that variations in genes that are linked to ghrelin and GLP-1 are associated with high alcohol intake and higher risk of alcohol addiction.
“Finding these associations in genetic studies provides an initial clinical implication. And that’s the ultimate goal of my research,” says Elisabet.
“Finding new medicines that can help patients with alcohol addiction.”
TEXT AND PHOTO: ELIN LINDSTRÖM CLAESSEN