Medicine and Health

During an ordinary influenza season, around 500 000 persons around the world die. It is in particular persons with weakened immune systems, small children, and old persons who become seriously ill and die. Influenza viruses can be transferred to humans from other animal species. They can also mutate rapidly and create pandemics. The World Health Organization (WHO) lists influenza as a constant potential threat against public health.

Increased knowledge of exactly how influenza viruses cause disease and how our immune systems react is important to enable high-risk patients to be identified and helped, to develop new therapy methods, and to make us better prepared for a future pandemic.

In our project, we will investigate the possibility of defining the specific immune profile of an influenza patient early on in the disease, and whether it is possible in this way to predict the level of severity of the disease. We are particularly interested in understanding the role played by age in how the immunological response to influenza works.

To find this out, we will be studying immune system cells and immune responses in the airways – where the virus enters the body and multiplies – and in the blood of clinically well-described influenza patients with acute and convalescent disease. We will also study immune system cells in samples from airways of healthy control persons.

The research team works closely with the Karolinska University Hospital. The samples will be taken from persons during the influenza season and when the patients have recovered from their virus infection.

The aim of our research is to help influenza patients by predicting the severity of the disease better and earlier, and thereby make more targeted treatment possible. The studies will also provide basic knowledge about how influenza arises and develops, which is important ahead of future virus outbreaks.

Project name: Respiratory immune responses in human influenza virus infection across age to understand what dictates disease severity

Project leader: Anna Smed Sörensen, Associate Professor at the Department of Medicine, Karolinska Institutet

Read about the project in the Swecris database External link.

Those who eat too much and exercise too little run the risk of developing Type 2 diabetes, liver inflammation, and heart attacks. These ‘cardiometabolic’ diseases are the most common causes of death around the world. They are often studied in mice – but also in dogs and monkeys for example – by giving the animals too much to eat. The problem is that this does not lead to the same disease progression as in humans. Our research has shown that animals and humans respond differently to dietary change, and that overweight leads to different types of changes also inside the cells.

For this reason, we are looking for better alternatives.

During the last 20 years, we have led the development of two promising alternative methods: One is studying cells direct from humans of differing weights, or growing on these cells into small mini-organs that we put together into small multi-organ chips. With the second model, we create digital twins using information from many different data sources. With the help of these, we can simulate what happens in the different organs of the human body when you eat and exercise, for example.

In this project, we will for the first time combine these two models into one. The basic idea is to make our digital twins scaleable.

This entails scaling down the twins until they only cover the organs that are held on the small chips. Then we can for the first time measure flows inside the cells during various disease conditions and therapies. On a computer, we then scale up the small mini-organs into human versions. In this way, we can make a much better translation of results from chips to humans.

This new combination of methods can lead to a new type of knowledge-driven medicine development that saves time and money for researchers, companies, and public agencies.

Project name: Scaling from microphysiological systems to humans using scalable digital twins

Project leader: Gunnar Cedersund, Associate Professor at the Department of Medical Technology, Linköping University

Read about the project in the Swecris database External link.

The clinical success of immune-activated antibodies for treating certain cancer forms has led to immunotherapy soon becoming part of the standard therapy for ever more cancer patients. But for many patients with triple-negative breast cancer, the chances of receiving this type of therapy are less good. The reason is that we lack knowledge of how the immune system recognises the tumour cells.

In this project, we will collaborate with experts at SciLifeLab to close down one gene at a time in TNBC cells, that is, triple-negative breast cancer, and assess whether this favours or counteracts the immune system’s ability to recognise the cancer cells. We have discovered new functions in several proteins that can affect how immunotherapy works. Further research is being done to investigate functions of proteins in TNBC cells. The project will be using the extremely exact genetic scissors CRISPR. With its help, we can modify the genome in selected locations in the cancer cells.

Our ambition is to obtain important knowledge about the interaction between the immune system and the TNBC cells, and thereby speed up the development of immune therapy for patients with triple-negative breast cancer.

Project leader: Yumeng Mao, Researcher at the Department of Immunology, Genetics, and Pathology, Uppsala University

Project name: Genome-wide discovery of cancer intrinsic immune resistance mechanisms in triple negative breast cancer

Read about the project in the Swecris database External link.

In Sweden, around 24 000 persons fall ill with dementia every year, and there is no cure. Investments in precision medicine – finding the right therapy for each individual person – are now being made in a number of different areas, but to date the corresponding investment has not been made for dementia diseases. More research is therefore needed to clarify the links betwen different disease mechanisms and specific dementia diagnoses, and what treatment works best in each scenario.

In our project, we will identify different risk groups. For example, persons with greater genetic risk can have a greater risk of developing dementia. We will also be identifying many other factors that play a role: Gender, age, biological age, how good the cognitive ability is, and whether a person has a metabolic variation or not. We will also be analysing whether specific medicines can help to prevent dementia. A person with vascular dementia, that is, blood vessel dementia, may benefit more from lowering their cholesterol level than a person with another type of dementia. These analyses are done with the help of large-scale epidemiological data, and also in a clinical data collection from geriatric patients in Stockholm.

To slow down the development of dementia disease, many different medicines will probably be needed in the future. Treatment may also need to be started at an earlier stage. It is our hope that our results can contribute to an improved strategy with new guidelines for dementia prevention in healthcare.

Project leader: Sara Hägg, Associate Professor in Molecular Epidemiology, Karolinska Institutet

Project name: Towards a pREcision medicine Approach to Target Alzheimer´s Disease and Related Dementias (TREAT-ADRD)

Read about the project in the Swecris database External link.

Around half of all women of fertile age have one or several myoma in the womb. Although myoma are harmless muscle knots, they can cause heavy bleeding and stomach paim, pregnancy complications, and childlessness. The few medicines that exist today improve the symptoms in many women, but not all. There is currently no knowledge of why the effect varies, or how it can be predicted in advance which myoma will shrink with medication.

New research has shown that there are several distinctive sub-groups of myoma, with characteristic differences. By comparing the effect of the medicine ulipristal acetate on the most common sub-groups, we have found that myoma belonging to a certain sub-group tend to respond better to treatment.

With the help of tissue samples from women operated on for myoma, we now want to find out if we can classify myoma into sub-groups to predict how well they will respond to different types of medicines. In the long term, this can lead to tailored treatment. We also want to identify markers that could be used in the classification, and investigate whether it is possible to do a classification with the help of a simple blood test.

Improved opportunities to diagnose and treat myoma of the womb would be of benefit to millions of women around the world.

Project leader: Lauri Aaltonen, Professor, Department of Biosciences and Nutrition, Karolinska Institutet

Project name: Towards individualized treatment of uterine fibroids

Read about the project in the Swecris database External link.

Sweden is one of the few countries where children born following donation treatment have a legal right to find out the identity of the donor. Those who donate eggs or sperm must therefore accept that their identity may be disclosed.

The purpose of our project is to investigate the long-term psycho-social consequences of donation treatment for all those involved – children, parents, and donors. Particular focus will be on issues that relate to the child’s right to find out that they were conceived through donation treatment, and who the donor is.

The project is based on a national study of egg and sperm donation that started in 2005–2008. It covers 300 donors and 894 men and women who underwent donation treatment. We will be sending surveys to all donors from that study, and to the couples who have become parents. Via the parents, we will ask permission to contact the children, who are now teenagers (15–17 years) and will soon have the legal right to seek information about their donors.

There is currently little knowledge of what long-term psycho-social consequences this type of treatment has for all the parties involved. The results from the project can contribute to developing clinical care and psycho-social support for children, parents, and donors.

Internationally, there is a lively debate about children’s right to know their genetic origin, and the development in Sweden is monitored with great interest.

Project leader: Claudia Lampic, Professor of Clinical Psychology, Umeå University

Project name: Long-term follow-up of the ‘Swedish Study on Gamete Donation’ - psychosocial consequences for families and donors 15-18 years after donation

Read about the project in the Swecris database External link.

Today, one in three children develop allergies. In parallel with allergy and asthma becoming more common, microbial diversity has reduced due to our modern lifestyles.

The measures for reducing infection spread during the COVID-19 pandemic has led to lower exposure also to other infectious agents. This can have consequences for the development of the immune system and increase the risk of allergies. Furthermore, stress and deteriorating mental health increased in pregnant women during the pandemic, which may affect the foetus’s immune system.

The pandemic made it possible to investigate how infection-prevention measures, stress, and mental health during pregnancy affect the gut flora, the development of the immune system, and the risk of children developing allergies.

We will be comparing 500 children born before and during the COVID-19 pandemic, to find out how infection-preventing measures have affected the gut flora. Our plan is to monitor children in 10 000 families, from birth up to the age of seven.

The results can be used to prevent children from devloping allergic diseases. Parents are generally very prone to changing their lifestyles during pregnancy and the child’s early years if this can improve their children’s future health. For this reason, preventive strategies for risk groups during this period of life can have considerable effects.

Project leader: Christina West, Professor and Senior Consultant in Paediatrics, Umeå University

Project name: Determinants of microbiome development and relation to allergy risk in childhood before and during the COVID-19 pandemic

Read about the project in the Swecris database External link.

It is often said that healthcare can save large amounts of money by switching to digital healthcare appointments via video and chat, in particular primary care, which is responsible for the greater proportion of all healthcare appointments in Sweden.

This can be done by care providers becoming more productive compared to when they use more traditional ways of caring for patients; that is, they can provide more care for a given amount of money. Or else the care itself becomes more effective; that is, the patients get well sooner, or the need for subsequent appointments reduces. There is currently no proof that digitisation has led to this.

The purpose of the project is to study whether health centres and on-call centres that use more digital forms of primary care are also more productive, and if their care is more effective.

We will be analysing information on how care providers use digital healthcare methods. To enable the effects of digital primary care to be calculated, we will analyse patients’ diagnoses and types of appointments from the period before and during the COVID-19 pandemic. The results can contribute to decision-makers making more informed decisions about how resources should be divided up between different types of primary care.

Project leader: Björn Ekman, Researcher in social medicine and global health, Lund University

Project name: Evaluating the impact of digitalization on the productivity and effectiveness of primary care in Sweden

Read about the project in the Swecris database External link.

Textbooks state that only thin nerve fibres signal pain in humans. In other mammals, it has been possible to prove that also thick nerve fibres can transmit pain.

Our research team recently made a fundamental discovery, namely that humans too have thick nerve fibres that signal pain. We call them ‘ultra-fast pain nerves’ as they transmit pain at very high speed.

To learn more about these pain nerves, we now want to investigate both healthy persons and persons with rare mutations that affect the sensitivity of skin. We want to find out how the ultra-fast pain receptor functions, right down to molecular level. We have, for example, seen indications that the nerve becomes more sensitive following inflammation. If this is correct, it could be of great importance for pain that arises after tissue damage. Such a discovery could lead to new medicines against pain.

We also want to investigate whether ultra-fast pain fibres play a role in the reflex that make us quickly withdraw the foot if, for example, we step on a tack. We have developed a new method for measuring this reflex.

The project is expected to be of great importance for continued pain research, and will probably lead to patients who are experiencing pain being better looked after and receiving a better diagnosis.

Project leader: Saad Nagi, Senior Lecturer at the Department of Biomedical and Clinical Sciences, Linköping University

Project name: Pain in the ultrafast lane

Read about the project in the Swecris database External link.