Parkinson’s treatment minus side effects
A new drug combination may be able to eliminate the negative side effects of medicine used for treating Parkinson’s disease.
Drugs used for treating Parkinson’s disease often have side effects that are disabling for the patient. But trials with a new drug combination show it can potentially eliminate these side effects.
One of the most effective – and widest-used – drugs currently on the market for treating Parkinson’s disease is Levodopa, which is most frequently given to older people or to people severely affected by the disease. But after several years of treatment with Levodopa, 80 percent of patients experience severe negative side effects.
One of Levodopa’s side effects is dyskinesia, a movement disorder seen in the form of involuntary movements or spasms. Over time, these can be so violent in some patients that their doctors see a need to reduce the patient’s drug dose – and thus the treatment.
Such side effects may be eliminated before long by a combination of two existing, known drugs that was discovered by Danish biotechnology company Concit Pharma, which has yet to publish the names of the drugs.
“The medicine used to treat Parkinson’s disease isn’t perfect,” says John Bondo Hansen, who holds a PhD in medicinal chemistry and is one of Concit Pharma’s founders. “This medicine very often induces some severe side effects – and you must either accept them or a lower dose that gives poorer treatment.”
Hansen explains that his company used some drugs that have already been thoroughly tested “because we wanted to improve the patients’ treatment quickly. In fact, things have happened so quickly that we have yet to find a name for the new drug combination.”
Animal trials to verify results
Clinical trials of the new drug with patients should start in the second half of 2012. Concurrently, the Neurobiology Research Unit (NRU) at the Copenhagen University Hospital, will start a new trial with the drug combination on rats and mice to verify initial test results showing that the combination works as expected.
In this two-year trial, the animals’ behaviour will be monitored after they have been given Levodopa and either the new drug combination or a placebo with no drug content, says Morten Skøtt Thomsen, a postdoc at the NRU.
“Initially we want to verify the effect of this drug combination,” says Thomsen. “The first tests had some very positive results, and we now want to see if they are valid and then find out whether the combination of drugs can be improved.”
Brain cells die from Parkinson’s disease
Although the animals’ behaviour is Thomsen’s prime focus, he will also measure the levels of various biomarkers and dopamine, which are closely related to Parkinson’s disease, and study how the drug combination affects the brain’s production of dopamine.
Dopamine is a reward response substance in the brain and it is generated by e.g. physical activity and when we predict a situation correctly.
In people suffering from Parkinson’s disease, some of the brain cells that normally generate dopamine are dead. This is particularly true in a region of the brain that regulates the body’s movements. The disease is therefore mainly characterised by muscle rigidity, shaking and reduced and slow movements.
Levodopa contains a form of precursor to dopamine and this helps the brain generate the dopamine it lacks. Although the cause of Levodopa’s side effects is unknown, Thomsen says they could arise because the dopamine from this source is not as finely regulated as that produced naturally by the brain – and this may impact negatively on brain areas with sufficient dopamine.
According to another researcher, Stephen W. Pedersen, a consultant at the department of neurology at Glostrup Hospital, it is not known whether Levodopa is the actual cause of the side effects.
“Some experts argue that dyskinesia is a product of the disease and is triggered by Levodopa,” he says. “Dyskinesia often arises after many years of high doses of the drug, and in people who also get other medicines at the same time, so it is unclear whether Levodopa is the cause.”
Pedersen says it is important to remember that dyskinesia first arises after many years’ treatment with large doses of Levodopa, and that there are different degrees of severity of dyskinesia.
“Otherwise people will stop taking Levodopa – which is the most effective treatment for Parkinson’s disease currently on the market,” he says.
Concit Pharma believes that its new drug combination can also be used to treat the side effects of medicine for other movement-related ailments, such as tardive dyskinesia, which is a side effect of drugs treating schizophrenia.
Read the article in Danish at videnskab.dk
Translated by: Michael de Laine
