So why is this group of diseases so poorly known?
Because it is comprised of hundreds of diseases with extremely varying characteristics.
And then there’s the name! For now, there is no simple term covering the entire spectrum of these diseases, as there is the word cancer for all malignancies. Maybe mito could serve as such a term?
Why, then, is it worth investigating these diseases unknown to most? Actually, thousands of patients are suffering from mitochondrial diseases in Europe alone. There are as many patients with mitochondrial diseases as there are children with cancer. And, unlike in the case of certain cancers, there are no curative treatments for any mitochondrial diseases.
“Is there a need for research that aims to find treatment for fatal brain and heart diseases of children? Is there a need for research focused on finding therapies for severe epilepsy manifesting in a teenager? Or for an adult-onset disorder causing balance problems, cognitive decline or cerebral infarctions?” asks Academy Professor Anu Wartiovaara who has studied mitochondrial diseases since the early 1990s.
“People don’t understand the origins of cancer either, but everyone knows that cancerous diseases must be studied and treatments must be developed. My goal is to make ‘mito’ as well known a concept as cancer, spreading knowledge about the progressive, devastating disease group” says Wartiovaara.
Identical genetic background of diseases is not the full story
Common to all mitochondrial diseases are dysfunctional mitochondria in cells. Mitochondria are cellular components that provide us with the energy upon which our lives depend. Through them, the oxygen we breath converts the food we eat into energy used by cells. A dysfunction in this production chain is obviously always problematic.
Mitochondrial diseases and the diversity of related symptoms originate in the multitude of ways mitochondrial functions can be disturbed.
“We have found hundreds of gene mutations underlying these diseases, in both our nuclear genome or in mitochondrial own DNA. However, disease can manifest in different ways even in patients carrying the same genetic error. One person may suffer from a severe brain disorder from an early age, while another has an adult-onset heart disease. What is the underlying mechanism in such variability? That’s what we are interested in, since these mechanisms are the key to treatment discovery,” says Wartiovaara.
Wartiovaara has indeed come to the conclusion that treating mitochondrial diseases should be studied in patient groups that have similar clinical symptoms, instead of paying attention only to an identical genetic background.
“Around the world, practical treatment options may have been overlooked due to excessively mixed research designs: some patients might benefit from a trial treatment even though this benefit may not be noticeable on the scale of a diverse patient group.”
Wartiovaara’s group has begun structuring new kinds of clinical studies where, in addition to the genetic background, natural history of disease is carefully studied and the clinical similarity is a key criterion to select the patients into the study.
“In Finland, we have an excellent opportunity to conduct such research. Finns as a nation are genetically quite uniform. Of particular value is also the way how patients and their families are positive toward research and commit and participate in studies.”
Living with MIRAS
The disease known as MIRAS had not even been discovered in 1992 when Kim Storås, a healthy 14-year-old, began experiencing strange seizures. The diagnosis was epilepsy, which was treated with commonly used epilepsy medication.
“At the time, it was not known that the medicine was particularly dangerous to MIRAS patients, causing severe liver damage,” explains Storås. He ended up at the Children’s Hospital, waiting for a liver transplant. Finally, he received a new liver in June 1993.
Another thing he received was a new diagnosis: Wilson’s disease. Despite its seriousness, the disorder is treatable, and many people with the disorder can lead fairly normal lives. That is exactly what Storås did after the liver transplant: he lived the normal and happy life of an adolescent.
“A couple of years later I started to feel pain in my legs. The problem was pinpointed to my hips, and in the end, hip prostheses were implanted in both legs. Rehabilitation took its time, but I decided to take part in the senior ball with my classmates, which I did.”
Storås completed studies in nursing and began to work.
In 2009, a transplant surgeon suddenly contacted him.
“They were conducting a study and he wanted to collect a blood sample from me. A little later I was called to the clinic, where I learned that I did not have Wilson’s disease after all, but a mitochondrial disorder known as MIRAS.”
Even as a health care professional, Storås was almost entirely unfamiliar with mitochondrial diseases, let alone one called MIRAS.
I believe that one day, a treatment for will be found. It may not come soon enough for me, but at least for others.
MIRAS, or mitochondrial recessive ataxia syndrome, was first described in a doctoral dissertation by Anna Hakonen, published in autumn 2008. The dissertation was completed in a research group led by Professor Anu Wartiovaara. MIRAS is a progressive neurodegenerative disorder manifesting with diverse symptoms. Common symptoms include, for example, ataxia, dysarthria, neuropathy and severe epilepsy.
Over the years, Storås’s disease has progressed, with worsening symptoms. Regardless, he held out at work until 2016.
“Lately, I have had to resort to using a wheelchair, since my balance is so bad and falling with hip implants is particularly hazardous. I am living one day at a time.”
Breakthroughs on the horizon in the field of nutrition?
Surprisingly, Wartiovaara says that the first breakthroughs regarding the treatment of mitochondrial diseases may well come from the field of nutrition. Wartiovaara’s interest in the effects of vitamins and nutrition on metabolism originates in basic research: scientific knowledge gained from mitochondrial disease models.
“Actually the effect of food is entirely logical. Mitochondria convert the food we consume into energy and cellular building blocks, so it is not neutral with what kind of nutrition the cells are fed,” she points out. Certain trace elements, such as vitamins and cofactors, are powerful regulators of energy metabolism. “But we need to know which of them are useful for a specific disease – vitamins are not harmless either”.
“In light of research findings, it is looking increasingly clear that healthy nutrition may mean something entirely different to those suffering from a mitochondrial disease compared to healthy individuals, while a certain diet may not be equally suitable even to patients with different mitochondrial diseases.”
In research conducted by Wartiovaara’s group, links between mitochondrial diseases and vitamin B metabolism were found. Currently vitamin B3 therapy is being tested in the treatment of mitochondrial diseases expressed in muscles.
Further findings of interest were gained in a study where a low-carbohydrate diet was trialled in patients with PEO (progressive external ophthalmoplegia). At first, the diet caused muscular damage, but this was not permanent: the patients recovered and their muscle strength was not diminished in the long run – for some, muscle strength even improved compared to before the diet.
Talk of vitamins easily leads to misinterpretations
“Society considers dietary supplements ‘only vitamins’, and misinterpretations and generalisations are common when talking about their dangers and treatment responses,” notes Wartiovaara.
“If I am recommending a certain dietary supplement to a patient suffering from a mitochondrial disease, my recommendation is based on our molecular studies understanding how this specific substance is tweaking the direction of metabolic flow in a particular disease. This knowledge does not mean that the recommendation applies to everyone, or even to another patient with another mitochondrial disease.”
Knowledge gained through disease studies has spurred Wartiovaara to ask how nutrition affects the metabolism of healthy children. A vegan food experiment conducted by the City of Helsinki at certain daycare centres provided the researchers with an opportunity to collaborate with the City, to investigate the metabolism of healthy infants eating vegan or mixed diets.
“We are combining expertise in nutritional science and molecular medicine. It is great how enthusiastically parents and their children have participated in this study.”
Videos: Helena Hiltunen