Movement disorders and neurodegeneration
Studies in Parkinson’s disease
Pharmacokinetics of levodopa are important for symptom control in Parkinson's disease (PD). A strategy to smooth out the levodopa concentration-time curve is to use a gel formulation of levodopa/carbidopa for intraduodenal administration. This strategy was developed in our department. Pharmacokinetic-pharmacodynamic studies are undertaken to improve therapy of motor fluctuations in PD. Microtablets of 5/1.25 mg levodopa/carbidopa are under investigation. Studies on pharmacoepidemiology, objective movement analysis, a test battery for self-reported subjective and objective functionin Parkinson’s disease are ongoing. A randomized study between deep brain stimulation and intestinal levodopa/carbidopa gel infusion is supported by the Swedish Research Council. This is a multicenter study coordinated from Uppsala.
Proteomics and biomarkers in neurodegeneration
The underlying causes of amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and atypical parkinsonism such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are largely unknown. The accumulation of protein aggregates in neurons is thought to play a role in the pathogenesis of these disorders, and therefore studies of protein expression in tissues from patients suffering from these conditions may be of importance for the understanding of the pathogenic mechanisms and may also result in the identification of biomarkers for these neurodegenerative diseases. Biomarkers may be used for early diagnosis, when symptomatic treatment is of clinical value for the patients and for following of disease progression. In collaboration with the Department of Physical and Analytical Chemistry, peptides and proteins from CSF from patients with ALS, PD, MSA and PSP and muscle biopsy specimens from patients with ALS are investigated by masspectrometry. Screening for potential protein biomarkers in plasma from patients with PD is performed in collaboration with the Human Proteome Resource group (HPR) at the Rudbeck laboratory and the Royal Institute of Technology (KTH) Stockholm. Biomarker studies in Huntington’s disease are planned. The differential diagnosis between PD andatypical parkinsonism is often difficult to make. We have used PET as a diagnostic tool with the tracers 11C-L-DOPA and 18F-deoxyfluoro-D-glucose (FDG). We are, in collaboration with the PET-centre, performing a retrospective analysis of all these investigations and relate the findings to clinical parameters and the clinical outcome. We are also performing PET with a new promising dopaminergic tracer (PE2I) in patients with different types of parkinsonism.
The neurology clinic in Uppsala, as the first Swedish center to use Botulinum toxin in clinical practice, has a longstanding experience of this treatment for a broad range of clinical disorders, such as cervical dystonia, spasticity after stroke and hyperhidrosis. Our research is
focused on defining the optimal use and dosage of Botulinum toxin for various clinical indications, as well as on analysis of the effects on symptomatic relief.
Quality of life in patients with ALS and their next of kin
Most studies of psychological health, quality of life and coping strategies in patients with ALS and their next of kins have been performed in North America and in European countries where the social welfare systems are different from that in Sweden. In a prospective study with a longitudinal and descripive design we are examining psychological health, quality of life and coping strategies in patients with ALS and their next of kin. The results may be of value for the future care of patients and the support of their next of kin.