Published 3.10.2024
Text: Laura Kytövuori
Image: Shutterstock
Editing: Viestintätoimisto Jokiranta Oy

 

When I started studying Parkinson’s disease, I waited for the first patient samples quite impatiently, with a strong feeling that this would become my life’s work. I also served as a contact person for patients, and one day I received a phone call that I will always remember: an anxious elderly man wailed on the phone that my research comes ten years too late and would not help his wife who was suffering in the final stage of the disease. The old man was crying – and so did I.

After the phone call, I had a devastating feeling of insufficiency. What if my research would not be of help to anyone? Later on, I have met plenty of patients and their loved ones. These meetings are the most meaningful part of my work. Parkinson’s disease concerns, in particular, elderly persons who are worried about their spouses and the younger generations, not really about themselves.

 

Risk factors include ageing and male sex

Globally, Parkinson’s disease is among the most extensively studied diseases. The disease is typically diagnosed when it has reached the phase where motor symptoms, such as tremor and rigidity, begin to cause harm in daily life. The majority of patients, however, have several other symptoms already before the actual motor symptoms. Parkinson’s disease reduces the quality of life and is associated with a significant level of comorbidity. While there is no cure for the disease nor any treatment to delay its progression, the only option is symptomatic treatment.

The most important risk factors for Parkinson’s disease are ageing and male sex. According to the statistics of Kela, at the end of 2023, a total of 17,899 individuals in Finland had received reimbursement for medication that was prescribed for Parkinson’s disease or a comparable motor disorder. Thus, the disease is very common and a huge burden to our healthcare.

 

A wide spectrum of symptoms

In Parkinson’s disease, there is wide individual variation in the symptoms and disease progression. For some patients, a slowly advancing tremor is the most severe symptom, while others suffer more from motor rigidity and weakened balance. Similarly, the spectrum of non-motor symptoms varies individually from one patient to another. One might think that there are several different Parkinson’s diseases. What is common to them is the death of nigral cells in the brain and subsequent lack of dopamine. The pathogenesis of the cell death is unknown and probably there is more than one mechanism that leads to the disease.

For years, attempts have been made to identify various subtypes of Parkinson’s disease. Succeeding in the subtyping could improve the prediction and diagnostics of the disease. The features that are common to different patient groups might indicate a shared disease mechanism. The identification of disease mechanisms is a prerequisite for the development of treatments affecting the disease progression. For the time being, the subtyping efforts have not resulted in the desired outcome. In my research, the aim is to approach the subtyping issue from a new angle, that is, through muscle symptoms and muscle findings.

 

Broad collaboration

Muscle symptoms occurring in connection with Parkinson’s disease have been studied surprisingly little, given the fact that the weakening of muscle mass and power as well as other muscular symptoms are frequent in patients. It is known that muscular symptoms are a typical outcome if there are any disorders in the functioning of the mitochondria that produce energy for cells. There are up to 2,000 genes contributing to the mitochondrial function, and hereditary mitochondrial diseases appear to be much more common in the population than previously assumed.

The muscle sample material collected by our research team is unique, even in global comparison. We are looking for, in particular, mitochondrial abnormalities in the muscle tissue and cell samples collected from patients. We investigate the mitochondrial function in the tissue and in live muscle cells in real time. We also examine structural abnormalities of the mitochondria as well as biomarkers that are characteristic of mitochondrial dysfunctions. Our aim is to identify clinically significant patient groups with a mitochondrial pathogenesis of the disease.

About every fifth of our patients have close relatives with the same disease. The globally known hereditary forms of Parkinson’s disease are, however, very rare in Finland. The hereditary forms seem to accumulate in the population of Eastern Finland and the population that have migrated from Karelia in Russia. It can be assumed that, in these families, the genetic factors affecting the disease are located in such areas of the genome that have been difficult to examine with traditional methods. We now have access to advanced long-read sequencing technology, and it is probable that, in the coming years, we will be able to identify hereditary disease forms that are characteristic of the Finnish population. The identification of new genetic factors will provide information about disease mechanisms that can potentially be affected in the future.

For my research, I collaborate with a large national and international network of specialists in different fields. In Finland, the universities and university hospitals in Oulu, Turku, Tampere and Helsinki are involved. We believe that through collaboration we will be able to solve the mystery of the pathogenesis of Parkinson’s disease and hopefully offer patients more accurate diagnostics already in the near future.

 

 

 

 

Ph.D., Docent, Laura Kytövuori is currently working as Researcher for the University Hospitals of Oulu and Tampere. She has studied mitochondrial dysfunction in adult patients within a research team led by Professor (Emer.) Kari Majamaa at the University of Oulu. Currently, Kytövuori is the Principal Investigator in the PD-NEF (Parkinson’s Disease in North and East of Finland) project and, with funding from the Sakari Alhopuro Foundation, is engaged in the study of muscle findings in Parkinson’s disease.