Published: 01-11-2016 09:00 | Updated: 01-11-2016 11:07

Millions to KI researchers from the Erling-Persson Family Foundation

Three research project led from Karolinska Institute will this year share SEK 41 Million in grants from the Erling-Persson Family Foundation. Researchers at KI are also partners in a project led from the Royal Institute of Technology (KTH), which will now receive a large grant from the foundation.

In its support of scientific research the Erling-Persson Family Foundation prioritizes projects with a focus on medicine and healthcare. The Foundation has a preference for research that is close to the patient and application-oriented, as well as built on collaboration across scientific boundaries.

Platform for registry-based randomized clinical trials in heart failure

Project: A platform for and conduct of the first Registry-Randomized Clinical Trial in heart failure: The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFPEF)

Projekt leader: Dr Lars H. Lund, Department of Medicine, Solna, Karolinska Institutet.

Partners: The Swedish national heart failure registry, RiksSvik, and Uppsala Clinical Research Center.

Funding: SEK 10 Million over a period of three years.

To determine whether a medical treatment is effective, it needs to be studied in a randomized clinical trial (RCT). However, conventional RCTs are becoming increasingly complex and costly. The Registry-based Randomized Clinical Trial (RRCT) is a novel concept pioneered in Sweden that builds a trial platform on an existing health care registry to perform an RCT.

Heart failure is common, deadly and associated with poor quality of life. In heart failure, the patient suffers from an impaired ability to pump blood, or impaired ability to fill the heart with blood. Heart failure with impaired pumping is treatable, but heart failure with impaired filling is equally common and serious, and there is no proven therapy. Spironolactone is an existing inexpensive drug that reduces mortality in heart failure with impaired pumping. It is promising also in impaired filling, but the efficacy of this ‘new use’ of an existing drug needs to be proven in a randomized trial.

“However, this this will not be done by the industry, because spironolactone is generic, and industry has no incentive to finance research unless on a patent-protected drug”, says heart specialist and principal investigator Lars H. Lund. “The purpose of our project is therefore to test the in-expensive spironolactone, and at the same time build a platform for similar randomized clinical trials for drugs in the future.“

Improved prostate cancer diagnosis – further development of the Stockholm3 test

Project: The Individualized Prostate Cancer Diagnosis Pipeline

Projekt leader: Professor Henrik Grönberg, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet

Partners: Karolinska University Hospital, Stockholm County Council and Prostate Cancer UK

Grant: SEK 28 million distributed over three years.

Prostate cancer is the most common form of cancer in Sweden with over 10,000 cases and 2,500 deaths every year. The aim of the project is to reduce the number of deaths from prostate cancer by developing new and safer diagnostic tests that better identify and help treating aggressive prostate cancer and implement these tests in routine clinical care.

An important first step has already been taken with the development of Stockholm3 test, a blood-based prostate cancer test that combines genetic and protein markers. The Stockholm3 test was evaluated in 2012-2014 on over 58,000 men in the Stockholm region and the results have been presented in The Lancet Oncology and other medical journals. The studies have demonstrated the benefits of the test, which include a higher detection rate of aggressive prostate cancer and fewer men that need to take an unnecessary prostate biopsy.

The support from the Erling-Persson Family Foundation makes it possible to further develop new diagnostic tests for prostate cancer. One example is a combination of the Stockholm3 test and magnetic resonance imaging scans to further improve the identification of aggressive prostate cancer. The researchers will also develop methods for assessing tissue samples using genome sequencing and enabling the treatment of metastatic cancer, i.e. cancer that has spread beyond the prostate. They hope to clinically implement further improvements of the prostate cancer diagnostic pathway within three years.

“The Stockholm3 test is already available for men in Sweden via the Karolinska University Hospital Laboratory,” says Henrik Grönberg, consultant and professor of cancer epidemiology, who has also patented the test. “We’re now taking the next step, which means that we’re looking at how we can improve the whole prostate cancer diagnostic pathway. This will include developing and implementing new technology and improved processes, which will allow us to detect aggressive cancer earlier and reduce today’s problem of over-diagnosis.”

The elimination of Malaria in Zanzibar – a case study for Africa

Project: Is Malaria elimination possible in Zanzibar? A case study for Africa.

Projekt leader: Professor Anders Björkman, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Partner: Zanzibar Malaria Control Program

Funding: SEK 3 Million over a three year period.

Ever since the 1980s, Professor Anders Björkman and his group have been interested in strategies to decrease mortality and incidence of Malaria including novel methods for diagnosing and treating the disease. The research group has also focused on the evolution of resistance to new antimalarial drugs. In recent years, the research has mainly been conducted on Zanzibar, but also on mainland Tanzania, in Mali and in Guinea Bissau.

Zanzibar has been successful in decreasing the incidence of Malaria to a very low level – which is unique in an area with high endemic rates – and the research group is now continuing its work towards a possible total elimination of the disease. To achieve this, new intervention strategies have to be introduced, specifically targeting residual parasite reservoirs and using new surveillance tools and strategies, including new molecular surveillance tools. The aim of the project is to present a possible proof of concept concerning malaria elimination from a highly endemic region or a country. This would be globally unique.

Development of nanotechnology for the ultra-sensitive detection of blood-borne markers in lung and breast cancer

Project: Detection and analysis of tumour- and blood-borne markers using new nanotechnology for the early diagnosis and monitoring of cancer

Project leader: Professor Jan Linnros, School of Information and Communication Technology, Royal Institute of Technology (KTH).

KI researchers: Professor Rolf Lewensohn, and Dr Kristina Viktorsson, Department of Oncology-Pathology, Karolinska Institutet.

Other partners: Amelie Eriksson Karlström, professor at the School of Biotechnology, KTH; Afshin Ahmadian, professor at the School of Biotechnology, KTH and SciLifeLab; and Björn Samel, researcher for Acreo Swedish ICT.

Grant: SEK 29.8 Million distributed over three years.

With solid tumours, tumour markers are important for revealing metastasis and predicting the effect of therapies, such as modern target-seeking therapy. Unfortunately, samples from the tumour are often difficult to take owing to the location of the tumour, and usually only a minimal amount of tumour is extracted that can be used for biomarker analysis. Normally, however, tumours secrete small amounts of tissue fragments (exosomes) into the blood that reflect the tumour’s RNA, microRNA and surface proteins. Freely circulating tumour DNA is also often found in the patients’ blood. Technologies are therefore needed that can identify tumour markers robustly and quantitatively from extremely small amounts of such material.

The project group at KTH, Karolinska Institutet and SciLifeLab will be developing silicon chip-based methods using nano-biosensors to isolate exosomes and other material to study their protein, RNA and microRNA expression. The function of the sensors is based on the ability of antibodies and other so-called binders to capture and bind tumour-exosomes, allowing the measurement of the signal pathways – something that, in turn, reflects the properties of the tumour.

In this way, the group wants to create methods for early detection and diagnosis of cancer but also to reveal the presence of therapeutic tumour targets such as; mutated cell receptors like EGFR and EML4-Alk important in lung cancer.The researchers’ focus will be on samples from patients with non-small cell lung cancer, the most common form of this disease, and breast cancer. Besides diagnostics blood samples will also be analysed during lung cancer treatment with target-seeking drugs towards mutated growth factor receptors orimmunological signaling pathways.

“Thanks to this generous donation from the Erling-Persson Family Foundation, we hope that our partnership with KTH will lead to an analysis platform based on nanochips for biomarker studies of tumour and blood, and thus to a new tool for more effective personalised cancer treatments,” says Professor Lewensohn.