Personalised treatment of Parkinson’s disease provides greater reliability

Dag Nyholm, a specialist doctor and professor of neurology, together with his neurology research group, has studied the optimisation of the treatment of Parkinson’s disease. The most important treatment for Parkinson’s disease is a drug called levodopa, named after to the substance L-dopa that is converted into dopamine in the brain.

“Levodopa is an effective treatment for Parkinson’s disease, but it also has its disadvantages and we have tried to solve these with three different formulations of levodopa,” says Dag Nyholm.

“These include what is known as a microtablet and two different pump variants where the solution is pumped into the patient. Most patients feel equally well with the optimised treatments as they have done in the years prior.”

Less and less effective over time

The treatment of the symptoms is effective, however, after five years, problems begin to emerge for approximately half of the patients. From a reliable effect, the medicine begins to be less and less effective. Simply increasing the dosage creates problems with severe side effects in patients, such as sudden movements.

“These include involuntary movements such as a spasm of the neck or irregular movement of an arm, which is very logical,” explains Dag Nyholm.

“Parkinson’s disease means that patients have reduced mobility and because the treatment with dopamine increases mobility this can in turn lead to too much mobility. The challenge is to fine-tune and achieve sufficient effect without side effects, which is referred to as the therapeutic window.”

Precision medicine reduces side effects

In the first few years, levodopa in tablet form therefore works relatively well, but it is difficult to establish the right dosage. In order to provide exact doses at short intervals, the Flexilev 5-milligram tablets and the Duodopa pump were invented by Sten-Magnus Aquilonius, professor emeritus of neurology. Further research has then been carried out over the years. In 2018, the latest treatment, Lecigon, was approved by the Swedish Medical Products Agency.

The most recent invention is a further development of Duodopa, with three instead of two active substances. The third substance allows patients to use levodopa a little more frequently, lowering the dose, but with the same effect.

“In published studies, we also have results that show patients are happy that the sizes of the pump and the ampoule are smaller, making it easier to carry with them. It improves daily life and is something that patients have requested for many years. Now we have been able to satisfy this need,” says Dag Nyholm.

“We need to adapt to the exact needs of each individual, so it really is precision medicine. Our research shows that patient needs for levodopa vary between 200 mg and 4400 mg per day. So there is a twenty-two-fold difference in what different patients need. Parkinson’s is an incredibly complex disease, but that is also where the motivation lies, we want to make a difference for patients.”

Improved quality of life

For some people with Parkinson’s disease, life can be very debilitating. Their daily lives are limited by not knowing what their body's motor skills will be like from one hour to the next. Patients with the most problems are those who fell ill at a young age, around 30–50 years old. The average age of diagnosis and initiation of treatment is usually around 70 years of age.

“Our latest treatment provides reliability and predictability for the patient; they are given more freedom and are able to rely on their body more. The fact that the research advances have made it possible for patients to experience more years of active life with work and leisure activities feels great. However, the treatment only stops the symptoms, not the disease. That is the next challenge,” says Dag Nyholm.

Antibodies to stop Parkinson’s disease

A research study is currently underway at Uppsala University to detect early symptoms of Parkinson’s disease, known as prodromes. The cause of Parkinson’s disease is also yet to be identified. 

“The aim is to learn how to detect Parkinson’s at an early stage, perhaps up to two decades earlier than diagnoses are typically made today. Anyone between the ages of 50 and 75 is welcome to participate in the study via our website,” continues Dag Nyholm.

“We believe that healthy food, lifestyle and physical activity are important and that the cause of Parkinson’s disease is a combination of environmental and genetic factors. Research on this is also ongoing.”

The mechanisms of Parkinson’s disease are similar to those of Alzheimer’s disease. During the autumn, Lars Lannfelt’s research group and the pharmaceutical company BioArctic made a breakthrough with the lecanemab antibody to halt Alzheimer’s disease.

“If the development of the new BioArctic drug proves to be as good as we hope, Parkinson’s may be able to follow the same path to prevent the development of the disease with similar antibody treatments as those tested in people with Alzheimer’s. The hope is to be able to develop disease-modifying treatments. If that is the case, we want to be prepared and able to make early diagnoses. The ultimate goal is to stop the disease,” concludes Dag Nyholm.