Two ‘Spectacular' Studies & Other Movement Disorder Updates

Medscape

7 hours ago

This transcript has been edited for clarity.
Dear colleagues, I'm Christoph Diener, from the Faculty of Medicine at the University of Duisburg-Essen. In this month's video, I would like to concentrate on movement disorders.
We understand that biomarkers play a hugely important role in Parkinson's disease for identifying preclinical stages for differential diagnosis with multisystem atrophy and for the assessment of prognosis in people with manifest Parkinson's disease.
Prodromal Parkinson's and Two Spectacular Studies
There are a number of biomarkers, like alpha-synuclein in cerebral spinal fluid, serum, and skin biopsy, dopaminergic biomarkers, imaging, and neurofilaments. Although we have at present no disease-modifying therapy, there is a need to identify individuals in the prodromal stage of Parkinson's disease once these treatments become available.
There is a study based on the Health Professionals Follow-Up Study with 51,000 people and surveys between 2012 and 2017. In this particular manuscript, 6000 men were identified without Parkinson's disease. They were followed for 3.5 years, and 103 participants developed manifest Parkinson's disease.
Potential prodromal symptoms, such as constipation, hyposmia, and REM sleep disorders, were recorded. If three of these prodromal symptoms were present, the risk of developing Parkinson's disease in the next 3 years is increased by a factor of 23, and this shows how important it is to identify these prodromal symptoms early.
There were two spectacular publications in Nature , with a potentially new therapeutic approach for Parkinson's disease with the implantation of dopaminergic progenitor cells or blood-derived potent stem cells in the striatum in Parkinson's disease bilaterally.
One study in the United States with 12 patients, who also received immunosuppression, showed no serious adverse events and in particular no tumors, and an increase in 18Fluoro-DOPA uptake in the putamen in the high-dose group on PET. A second study in Japan with seven patients over 24 months showed no safety signals with clinical improvement in six patients and 18F-DOPA uptake increasing by approximately 45% on PET.
Both studies clearly show that stem cells can survive once they are implanted into the striatum. However, the clinical application is questionable, given the invasive nature and the high cost of these procedures.
GLP-1 Drugs Disappoint, and Subcutaneous Apomorphine
My next topic is GLP-1 agonists. There are epidemiologic studies and preclinical models that suggest the GLP-1 agonists, which are used for the treatment of diabetes and obesity, may be also effective in the prevention of neurodegenerative diseases. However, a randomized, placebo-controlled study with 2 mg exenatide per week subcutaneously vs placebo in 215 patients on dopaminergic medications showed no difference in the condition of medication.This is really frustrating, but further studies with different drugs are currently ongoing.
Continuous, subcutaneous apomorphine has long been used in Europe in patients with Parkinson's disease and serious fluctuations. There is an ongoing study in the United States with 85 patients over 52 weeks, which clearly showed that OFF times with continuous, subcutaneous apomorphine decrease over time with high patient satisfaction.The dose of levodopa can also be reduced. Typical side effects include local reactions, nausea, and somnolence. I think this is an important treatment, particularly in patients who cannot receive deep-brain stimulation.
Common problems associated with Parkinson's disease are falls and cognitive impairment.There was a small study that investigated an acetylcholine M 1 receptor-positive allosteric modulator called TAK-071 in 74 patients with at least one fall in the past 12 months. This was a crossover study with placebo over 6 weeks each.
Unfortunately, gait disorders and falls were not improved.Cognitive functions were slightly improved, but I think this does not justify the use of this drug in the near future in people with Parkinson's disease, falls, and cognitive impairment.
Dear colleagues, ladies and gentlemen, a few studies in movement disorders. The most spectacular, I think, are the two studies published in Nature .
I am Christoph Diener, from the Faculty of Medicine at the University of Duisburg-Essen. Thank you very much for listening and watching.