Doctoral dissertation

Dissertation: Body fluid biomarkers in MS: Special emphasis on biomarkers for PML risk assessment associated with natalizumab-treatment

Measurement of soluble L-selectin and JC virus encoded microRNA in the blood of multiple sclerosis (MS) patients may hold the potential as biomarkers to assess the risk of progressive multifocal leukoencephalopathy (PML) disease among MS patients treated with natalizumab drug.
Pabitra Basnyat -Photograph: Jukka Lehtiniemi

Multiple sclerosis is a chronic inflammatory autoimmune disease of the brain that leads to significant neurological disability, affecting mostly young adults, and the disease is more prevalent in women compared to men. Affecting more than 2 million people worldwide, Finland belongs to a high-risk region for MS affecting around more than 9,000 people, which is higher compared to previous years.

There is still no cure for MS but different highly effective drugs are available such as natalizumab, which can help speed recovery from attacks (relapses), modify the disease course, and slow down the disability progression.

Unfortunately, the longer use of this drug is associated with the serious risk of developing multifocal leukoencephalopathy (PML) disease in some MS patients. PML is a JC virus infection of the brain that damages the cells which make myelin, the material that covers nerve cells.

Currently there is no biomarker to predict the PML risk in NTZ- treated MS patient and currently this risk a major challenge for clinicians, because also other new effective drugs such as fingolimod and dimethyl fumarate were reported to carry this risk. Therefore, in the study soluble L-selectin and JCPyV microRNAs were analysed and found out that the measurement of these elements in the blood of MS patients could help to assess the PML risk during the natalizumab treatment, which may help patients for safe use of this drug for longer period and help clinicians to optimize the clinical decision in MS patients. However, these findings need validation in further studies.

MS is a single disease but its course and symptoms differ from person to person, and the disease may be active or inactive at different time points. Since there is no biomarker available that reflects the diverse clinical spectrum of MS, the other aim of this thesis was to find the biomarkers for evaluating MS disease activity.

This thesis identified the clinical significance of soluble CD26 and CD30 molecules in MS patients. Increased levels of these molecules in blood indicated the stable phase of the MS disease activity. Moreover, measurement of some genes such as TL1A in the cells of MS patients showed the association of this gene with MS disease activity and disability progression, and also holds ability to capture the effect of treatment response. These biomarkers will contribute to overall clinical management of MS patients with an ultimate goal to prevent the disease progression and development of long-term neurological disability. However further research are needed to validate these findings.

Pabitra Basnyat comes from Nepal. He earned a BSc. in Medical Laboratory Technology at Rajiv Gandhi University of Health Sciences, India and a MSc. in Biotechnology at the Tampere University of Technology, Finland. He currently works as Doctoral Researcher at the Faculty of Medicine and Health Technology at Tampere University.

The doctoral dissertation of MSc. Pabitra Basnyat in the field of neurology titled Biomarkers for Progressive Multifocal Leukoencephalopathy Risk Assessment and Disease Activity in Multiple Sclerosis will be publicly examined at the Faculty of Medicine and Health Technology at Tampere University on Friday, 15th of February 2019 in Jarmo Visakorpi auditorium of the Arvo building. The Opponent is Professor Anne Remes from University of Oulu. The Custos is Professor Jukka Peltola.

The dissertation is available online at http://urn.fi/URN:ISBN:978-952-03-1003-5