Tallinn University of Technology

The research group of mechanisms of neuronal death and survival at the TTÜ Department of Chemistry and Biotechnology led by Associate Professor Urmas Arumäe has, with support from personal research funding (i.e. funding for high level research projects), explored the possibilities for the treatment of neurodegenerative diseases for the last four years.

By now, the study performed in collaboration with the research group of the Institute of Biotechnology of the University of Helsinki led by Mart Saarma has reached an intermediate stage. The research focused on the mechanism of action of two proteins - MANF and CDNF.

"These molecules are unique proteins (factors) that attenuate cell death, i.e. promote cell survival and that are the most promising candidates at present for the treatment of Parkinson's disease and potentially other degenerative diseases. The mode of action of these factors is, however, poorly known," Associate Professor Urmas Arumäe explains.

Parkinson′s disease is a disorder in which nerve cells in certain areas of the brain start to degenerate (die) massively (for reasons that are unclear so far), causing gradual functional impairment of the relevant area of the brain and deteriorating significantly a person′s vital functions until death occurs. The cause for Parkinson's disease is yet to be identified by modern medicine, there is no cure, the progress of the disease can only be hindered.

The animal experiments carried out at the University of Helsinki indicate that infusing MANF and in particular CDNF proteins into the brains of animals with advanced Parkinson's disease like lesions not only halts the progress of the disease, but also reverses the damages leading toward to recovery from neurological damage. Thus, CDNF has proved to be the best candidate for the treatment of Parkinson's disease. If the clinical trials confirm efficacy of the drug, it will be a major breakthrough in the treatment of neurodegenerative diseases.

Associate Professor Arumäe says, "Most tissues are capable of regeneration, replacing the lost cells from stem cells, but most of the damaged neurons will never be replaced. The goal of our research was to understand the mechanism of action of MANF and CDNF factors. These are unique molecules, the mechanism of action of which is unlike the mechanism of action of any other protein. They can protect neurons intracellularly and extracellularly, no other such factors are known. However, so far very little is known about the details of the mechanism of action of these two factors."

The experiments carried out during the research identified two areas of MANF proteins that are necessary for the cell's life-sustaining function. This discovery is a leap forward in understanding the mechanism of action of MANF and CDNF proteins. This in turn provides better understanding of how these very promising drug candidates work.

"This research is a great step forward also in the treatment of other widespread, slowly progressive, but so far incurable diseases, such as diabetes, Alzheimer's disease, sclerosis multiplex, but also stroke, etc., since the first results indicate that MANF and CDNF may be effective in their treatment as well," Associate Professor Arumäe adds.

The research received new personal research funding until the year 2020.

Kersti Vähi, Research Administration Office