The goal of research into rare diseases is to find new and effective treatments

Together with the Finnish scientific community Orion is focusing on research into serious genetic rare diseases. Such diseases are still without treatments.

Above all, the purpose of research into serious genetic rare diseases is to find treatments that improve the condition of patients. Another aim is to produce tools and understanding that can be applied to other similar diseases and symptoms. This is according to director of the project Professor Antti Haapalinna from Orion and one of the partners Professor Reetta Kälviäinen from the University of Eastern Finland.

“Rare diseases are actually not very rare,” says Haapalinna, Global Head of the Therapy Area, Rare Diseases & Biologics, Biomarkers and New Modalities.

“In total over 60 million people in Europe and the USA suffer from a rare disease. It is estimated that there are about 6000–8000 different rare diseases.”

However, the number of patients per disease is low: in Europe, a disease is considered to be rare when it affects 1 person per 2000. In the USA, a disease is considered to be rare when it affects less than 200,000 in the USA.

36 genetic rare diseases in Finland

“80% of rare diseases are genetic. In many cases the disease is caused by a genetic mutation in a single amino acid. 75% of the rare diseases appear during childhood and 30% of the patients die of their genetic disease before they reach the age of five,” says Haapalinna.

Reetta Kälviäinen and Antti Haapalinna

36 genetic rare diseases have been discovered in Finland that are more common here than in the rest of the world. This Finnish disease heritage has been studied for nearly 30 years and the genetic mutations causing these diseases are known.

“Rare diseases include many degenerative illnesses that develop in the central or peripheral nervous system. These diseases are often under-diagnosed, as they may, for example, be mistaken for a more common illness with similar symptoms,” says Haapalinna.

“Though medical treatment has been developed for hundreds of rare diseases, most still lack current care guidelines and sometimes it is only possible to relieve the symptoms of patients suffering from these diseases.”

Treatments can be assigned special status

In the EU and the USA new treatments developed for serious rare diseases can be granted orphan drug status. The small number of potential users of the treatment is compensated, for example, by confirming a high reimbursable price for the drug, by granting the developer exclusive right to commercialise the drug and by supporting the marketing authorisation process.

“The key factor in the funding of the development work is that it may not be necessary to conduct expensive phase III trials on thousands of patients, and instead, as it is not easy to find patients, it is enough to conduct phase II trials that are carried out on fewer patients,” says Haapalinna.

Six teams of researchers

According to Haapalinna, there were several reasons why Orion decided to construct a new type of ecosystem based on researchers working together: to study the mechanisms of certain rare diseases, to create new technologies and above all to find functional treatments for these patients.

“In rare diseases our researcher partners have a deep understanding of the clinical progression of the disease and the factors of the disease that are the main problem for the patient,” says Haapalinna.

“Six different teams of researchers have been working on the project from the beginning of the year. Some are researching certain diseases, some are developing drug technologies and some are developing methods, such as biomarkers, genetic testing and other measurement methods. We will already be able to discuss the first patient results in October 2019.”

In order to demonstrate the efficacy of the drug actual measurable indicators are needed. In the worst case, if the wrong indicator has been selected, it will not demonstrate the efficacy of a functional drug.

New understanding and tools also being sought

Reetta Kälviäinen, Professor in Neurology at the University of Eastern Finland and Director of Epilepsy Center at Kuopio University Hospital, explains that the purpose of the project is to also gain new understanding and new tools that could be applied more broadly.

“In the final stage degenerative illnesses resemble each other and the mechanisms of two illnesses can be similar to a certain extent, even if their pathogenesis is different. There can also be mild and serious forms of the illnesses, and using the mechanisms of the milder version it might be possible to find out what factors protect patients from the more serious form,” says Kälviäinen.

“But even though it is important to gain information about the diseases, we, first and foremost, need effective treatments with significant benefits for patients. The need for treatments is significant as we have been able to offer these patients little more than support.”

Under-diagnosed EPM1 incapacitates patients at a young age

In Kuopio, a team lead by Kälviäinen is researching the EPM1 disease, which is also known as Unverricht–Lundborg disease. It is a form of progressive myoclonus epilepsy, which is caused by a mutation in one gene and which, even in its mildest form, is a serious and incapacitating disease.

Hundreds of people in Finland have EPM1. The disease usually onsets in children between the ages of 6 and 15 and its progression takes place in waves and very individually.

“The first symptoms resemble those of juvenile myoclonic epilepsy that has a good prognosis and the disease is often first diagnosed as this. It is usually possible to get seizures involving loss of consciousness under control and patients usually experience a stable phase during the teenage years and life can be very normal,” says Kälviäinen.

“However, muscle jerking or twitching (myoclonus) caused by various external stimuli and other mobility problems that belong to symptoms of the disease start to worsen in the end until they reach a climax, usually around the age of 25. Some patients are able to walk, some have to use a wheelchair and some require assistance with everything.”

The right diagnosis brings relief

Though EPM1 may not necessarily reduce life expectancy, this serious disease that starts at a young age is difficult to deal with mentally and often leads to depression.

“For this reason, in addition to treatment for their symptoms patients often require comprehensive personalised rehabilitation that aims at maintaining their neurological and cognitive functionality,” says Kälviäinen.

EPM1 is not just a form of epilepsy, it is also a movement disorder like Parkinson’s disease. Unfortunately, up to now treatment has only been available for the disease’s epilepsy symptoms and insufficient attention has been paid to the movement disorder nature of the disease.

“Though there is no cure for the disease, getting the right diagnosis is usually considered to be a good thing, as symptoms often start to get worse after the teenage years. Fortunately, the patients and their families are nowadays very knowledgeable on the subject and keep in close contact.”


Text: Jussi-Pekka Aukia
Profile: Jussi-Pekka Aukia


9 October, 2019