Karolinska Institute. Sweden: Involuntary dyskinetic movements induced by treatment with levodopa (L-dopa) are a common problem for people with Parkinson’s disease. Now, however, researchers at Karolinska Institutet and Lund University in Sweden seem to be close to a novel therapy to this distressing side effect. A treatment study published in the scientific periodical Brain shows that a drug that stimulates certain serotonin receptors in the brain counteracts the dyskinesia causing effects of L-dopa.
The substance tested by the team, eltoprazine, is a so-called
serotonin receptor agonist that targets receptor types 5-HT1A and
5-HT1B. Serotonin is a neurotransmitter involved in the regulation of
many biological phenomena, such as satiation, sleep and mental
wellbeing, as well as movement. Earlier research on animal models for
Parkinson’s conducted by Anders Björklund, professor of histology at
Lund University
, and Per Svenningsson, professor of neurology at
Karolinska Institutet
, showed promising results using serotonin receptor agonists against
L-dopa-induced hyperkinesia, and have prompted the researchers to
examine if the principle also operates in humans.
“Eltoprazine has been tested on patients in the psychiatric
field, but this is the first time a study has been done with Parkinson’s
disease,” says professor Svenningsson, who led the clinical study with
Håkan Widner, professor of neurology, from Lund University. “What’s
particularly exciting is that we’ve managed to translate laboratory
findings into clinical application.”
The study included 22 patients with protracted and complicated
Parkinson’s disease and L-dopa-induced dyskinesia. In the four-way
crossover study, patients were given a single tablet of placebo and
eltoprazine 2.5, 5 and 7.5 mg, alongside a challenge dose of levodopa
that was 1.5 times that of their usual L-dopa dose.
It was found that a 5 mg and 7.5 mg dose of eltoprazine both
significantly reduced the patients’ dyskinesia. At the same time, the
preparation had no adverse impact on the anti-Parkinsonian effects of
the L-dopa treatment. Other than a few patients having some transient
episodes of nausea, dizziness and other minor symptoms the treatment was
well tolerated.
“The treatment seems to be tolerated well by most Parkinson’s
patients and counteracts L-dopa-induced dyskinesia via a new mechanism
of action,” says Professor Svenningsson. “If our initial findings can be
confirmed, this type of therapeutic principle can be of immense
clinical benefit to a particularly vulnerable patient group.”
Even though eltoprazine has been around since the 1990s, it
still has not been registered, and the combination study reported here
was done on the initiative of the lead investigators themselves. The
study was partly financed with a grant from the
Michael J. Fox Foundation for Parkinson's research
. Recently, however, the rights to eltoprazine were acquired by the US biotechnology company
Amarantus BioScience Holdings, Inc
. The compound is now advancing into a larger scale, longer duration
study to evaluate the full treatment effect of eltoprazine in
Parkinson’s patients with L-dopa-induced dyskinesia.
Publication:
‘
Eltoprazine counteracts L-dopa-induced dyskinesias in Parkinson's disease: A dose-finding study
’, Per Svenningsson, Carl Rosenblad, Karolina af Edholm Arvidsson,
Klas Wictorin, Charlotte Keywood, Bavani Shankar, David A. Lowe, Anders
Björklund, Håkan Widner,
Brain – A Journal of Neurology
,
first online 10 February 2015.
For further information about this study, please contact:
Professor Per Svenningsson, MD, PhD
Centre for Molecular Medicine, Karolinska Institutet
Tel:+46
(0)8-517 746 14 or 070 749 85 22
E-mail:
per.svenningsson@ki.se
Professor Anders Björklund, PhD
Faculty of Medicine, Lund University
Tel: +46(0)703 -146761
E-mail:
anders.bjorklund@med.lu.se
Professor Håkan Widner, MD, PhD
Faculty of Medicine, Lund University
Tel: +46(0)46-171425
E-mail:
hakan.widner@med.lu.se