Good examples

Phenomena in the clinic raise research questions

Can herpes infection be an important explanation of why some individuals develop Alzheimer's disease? Hugo Lövheim, researcher and physician at the Geriatric Center at Norrlands University Hospital in Umeå, has seen a clear relationship in extensive population material. He is now conducting a clinical study to see whether it is possible to influence the disease process in Alzheimer's disease.

It is a late afternoon in August, the autumn is early in Umeå and the birches have already begun to turn yellow. Hugo Lövheim sets off the bike outside of Norrlands university hospital and shows the way through stairwells and winding corridors to the Geriatric Center. He is a physician and chief researcher for a clinical pilot study, the first in the world of its kind.

– It is a small study in which patients with Alzheimer's disease receive treatment with valaciclovir, an antiviral drug traditionally given in connection with herpes infections and effective to suppress the virus infection. Now we want to investigate whether this drug treatment can also affect basic disease processes of Alzheimer's.

Every year about 10,000 people fall ill in Alzheimer's disease in Sweden, the most common among our dementia diseases.

There has long been a suspicion that herpes (type 1 simplex virus, which causes common sores) may increase the risk of the disease in some individuals.

– Already in the early 1980s, researchers had seen that the form of inflammation in the brain caused by herpes simplex virus affects the same parts of the brain that are infected in Alzheimer's disease. But the results have been rejected by the research community, although no well-done studies have actually been done. I became curious and decided to move on scientifically and examine the hypothesis more closely.

Herpes and Alzheimer's

Hugo Lövheim is from the small village of Varuträsk, a few miles outside Skellefteå. As a little boy, he was curious about how things are interrelated and devoured thick reference books. The interest in science and people led him to apply for the medical program at Umeå University in 2001.

– Early on, I got interested in research and I started a PhD student project that I continued with during my residency.

The research project resulted in a dissertation that deals with elderly people treated with analgesics, or drugs for mental health problems. Hugo Lövheim showed that elderly people are far from being given optimal treatment and that the use of psychiatric drugs for the elderly in particular housing has increased significantly over the past 20 years.

After completing his dissertation, he continued to research alongside his specialist education in geriatrics. And it was in 2009 when he read about the hypothesis of a relationship between herpes virus and Alzheimer's disease that he decided to investigate epidemiological materials at Umeå University further. Data was obtained from the medical biobank and the Betulaproject, a population study on aging, memory and dementia in Västerbotten.

– With the help of materials from the biobank we can do studies that are unique. In our case, we have looked at patients diagnosed with Alzheimer's disease and then compared with biobank samples taken several years earlier when they were healthy.

Analyzes showed that the old hypothesis of the 1980s is still valid and there can be links between herpes virus and Alzheimer's disease. The results were presented in two scientific articles in 2015.

– In the laboratory environment, it has also been observed that herpes virus stimulates the production of the tau and beta-amyloid proteins, two typical markers for Alzheimer's, which makes the hypothesis even more interesting, says Hugo Lövheim.

His research team now works with the hypothesis that genetic factors in combination with the fact that the immune system deteriorate as we age, improves the conditions for the herpes virus to spread in the brain to the area where Alzheimer's disease begins.

– We are continuing our research to try to understand which people run a higher risk, but also how the time lines look so that we get a better understanding of when it is most effective to apply treatment to affect the disease processes.

Hypotheses into research

Hugo is a deputy lecturer at Umeå University, which means that he can divide his time between research and clinical work as a physician at the Geriatric Center.

– I think it's a good combination. Research work is stimulating and important. If we are going to develop new treatments and learn more about diseases, it is good to have a foot in patient care. Meetings with patients generate hypotheses that you can then test scientifically. As a doctor, you can detect certain phenomena in the clinic that you would like to investigate further and the research gives us the tools to systematically observe and carry out studies in a scientific manner.

What are the most important conditions for working with clinical research while being active as a doctor?

– Financing is an important issue. The county council's research funding with so-called ALF funds is an important source. In healthcare today there are high demands on production and extremely limited opportunities to engage in research while working clinically as a physician.

– It is also valuable that there is a clinical research center with a clinical trials unit that can assist with applications and have a good knowledge of regulations, permits and ethics testing. For example, if you want to do a clinical intervention study with medicines, an application to the Medical Products Agency may cover over 100 pages. Pharmaceutical studies should be conducted according to GCP, good clinical practice, and it is important to receive support and assistance in the application process.

How would you like to define clinical research?

All research that is important for understanding and treating diseases. Research on proteins and cells is important for understanding basic disease mechanisms. But we also need treatment and intervention research to better understand how to develop better treatment methods.

Do you have any advice for doctors who would like to do research?

– The supervisor plays an important role, and it is important to join a research group where you get support and opportunities to develop, and also have good opportunities for combining research with patient work.

What motivates you as a physician and a researcher?

– I think i is fun to ponder, think and investigate how things are interrelated. And it is exciting to be able to do your own studies, to see how the projects grow and to follow the results over time. At best we can develop methods and improve treatments that benefit our patients.

– I am also stimulated by the extensive collaboration between pre-clinical and clinical researchers and that there is a link between the lab and the clinic. We also collaborate with several other research groups to help us move forward.