The International Congress of Parkinson’s Disease and Movement Disorders is taking place this week (Oct 5-9) in Hong Kong. This is an annual meeting of Movement Disorders scientists and physicians from around the world. At the meeting, research findings are presented, often for the first time. APDA is there and is reporting exciting news and highlights. Below, Dr. Rebecca Gilbert shares summaries of this research as it is revealed, along with a key takeaway (in lay terms) to help understand what each particular project could mean for people living with PD.
Saturday, October 6, 2018
Zonisamide improves parkinsonism in DLB patients: A randomized phase 3 trial (P17 – Murata M, et al)
Zonisamide, a medication approved for use in seizure control, was tested in patients with Dementia with Lewy Bodies (DLB). 351 patients were randomized to receive either placebo, zonisamide 25 mg a day or zonisamide 50 mg a day, for 12 weeks. Motor scores of parkinsonism (which measures tremor, slowness, stiffness and balance issues) were recorded throughout the trial. The medication was well-tolerated and improved motor scores over placebo. Although after 12 weeks, cognitive scores were worse on zonisamide as compared to placebo, after longer follow up, this difference disappeared.
Takeaway – consider zonisamide for motor symptoms in patients with DLB.
Alleviation of freezing of gait in patients with Parkinson’s disease by high-frequency rTMS over SMA is associated with normalization of brain connectivity patterns (P32 – Mi TM, et al)
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive procedure that uses magnetic fields to modulate the activity of nerve cells in the brain. In this study, the stimulation was administered, by placing a coil against the scalp, to the supplementary motor cortex (SMA), an area of the brain that contributes to control of movement. The study investigated whether this procedure could help improve freezing of gait (FOG) in PD. Results suggested that high-frequency rTMS over the SMA can alleviate FOG in PD.
Takeaway – Although rTMS is not yet performed clinically for FOG, in the future, rTMS may be used as a treatment for FOG.
The anti-dyskinetic effect of the clinically-available 5-HT3 receptor antagonist granisetron in the 6OHDA-lesioned rat model of Parkinson’s disease (P251 – Kwan C, et al)
The powerful anti-nausea medication granisteron (brand name Kytril) was tested in a rat model of Parkinson’s disease and found to alleviate levodopa-induced dyskinesias.
Takeaway – More studies will be needed to see if granisetron is helpful for Levodopa-induced dyskinesias in people, and not just rats. However, because granisetron is already approved by the FDA for use as an anti-nausea agent due to chemotherapy and radiation, if trials do show that it works in people for dyskinesias, it will be able to be used right away for this purpose.
Sex differences by design and outcome in the Safety of Urate Elevation in PD (SURE-PD) trial (P380 – Schwarzschild M, et al)
The SURE-PD study tested Inosine, a chemical that can raise levels of uric acid, as a potential neuro-protective agent in people with early Parkinson’s disease. The results of the trial are currently being analyzed to see whether Inosine slowed down the disease in the trial participants. This poster reports that inosine produced greater increases in serum and cerebrospinal fluid urate in women as compared to men.
Takeaway – as the results of the SURE-PD study are analyzed, we will know more about whether Inosine is a neuroprotective agent for people with early PD. This poster suggests that there may be a difference between men and women in their responses to Inosine and it is possible that only women with early PD will benefit from taking Inosine.
Sunday, October 7, 2018
Multiple research initiatives were presented today which focused on the use of technology for the detection and monitoring of Parkinson’s disease (PD). Here is a selection:
Quantitative mobility metrics from a body-fixed sensor predict incident parkinsonism in older adults (P929 – von Coelln R, et al)
683 older adults without PD symptoms were evaluated with a belt containing sensors to measure walking and turning. The patients were also examined clinically. The metrics derived from a wearable belt sensor were able to identify older adults without PD who developed Parkinson’s symptoms over time.
Takeaway – In the future, a device may be used to screen patients for their risk of developing Parkinson’s disease.
Does the Parkinson’s Kinetigraph change clinical practice? (P1103 – Jones S, et al)
The Kinetigraph is a wearable watch-like device that is worn continuously for 6-10 days at home and records data on motor function and medication use. Information about the patient’s motor patterns (bradykinesias and dyskinesias) over time are represented in graphs and shared with the patient’s physician before an office visit. The current study concluded that the information provided by the Kinetigraph was used by the physician to change clinical practice.
Takeaway – Results like this will hopefully encourage more physicians to use this device or similar devices, thereby allowing detailed quantitative long-term information on the mobility of a PD patient to be accessible by his/her physician and influence treatment decisions.
The use of smartphone task derived features to predict clinical scores in Parkinson’s Disease (PD) (P1111 – Lo C, et al)
Current methods of evaluating patients with PD in the clinic involve testing that can be inconsistent from one examiner to another. Researchers are looking for more objective ways of scoring a patient’s motor symptoms. Smartphone apps assessing voice, balance, gait, dexterity, reaction time, rest and postural tremor were used to collect data from many PD patients and correlated to the clinical scores obtained in clinic. These objective smartphone assessments of voice and movement were able to predict the clinical scores among PD patients.
Takeaway – In the future, objective, quantitative data of how a PD patient’s motor symptoms will be easily collected, more accurate than current assessments of motor function, and used to influence treatment.
Objective monitoring of drug response in early PD patients using remote, at-home typing data through machine learning analysis (P1124 – Matarazzo M, et al)
Using information about how a person types – the amount of time spent on a key and the amount of time spent between keys — was analyzed as a way of monitoring drug response in an unmonitored setting, at home between office visits.
Takeaway – In the future it may be possible to collect more continuous data on motor function in PD without any additional wearable sensors beyond the interaction between a patient and his/her keyboard.
Monday, October 8, 2018
Resistance to Parkinson’s disease (PD) among LRRK2 mutation carriers is associated with higher plasma levels of urate but not its purine precursors (P1304 – Schwarzschild M, et al)
Leucine repeat rich kinase 2 (LRRK2) mutations are a genetic cause of PD. However, LRRK2 has incomplete penetrance, which means that not everyone with this mutation will develop PD. The reason why some people with the LRRK2 mutation develop PD and others do not is currently unknown. This current research showed that people with LRRK2 mutations who did not develop PD had higher blood levels of uric acid that those who did develop PD. This suggests that blood uric acid levels may be protective of PD in the setting of a LRRK2 mutation.
Takeaway – It is possible that a medication that raises uric acid levels could be neuroprotective in people with LRRK2 and other mutations. This is the hypothesis being tested in the SURE-PD trial which is currently underway investigating the compound inosine, which raises uric acid levels, as a neuroprotective agent in PD.
Bidirectional gut-to-brain and brain-to-gut propagation of α-synuclein pathology in non-human primates (P1663 – Arotçarena ML, et al)
A common hypothesis is that abnormal alpha-synuclein molecules (which form Lewy bodies (LBs)) enter the brain via the gastrointestinal (GI) tract (see my blog for more on this topic). This current research injected LBs into the gut of non-human primates and saw development of LBs in the nervous system of the GI tract as well as in the brain, in keeping with the well-accepted hypothesis. However, in animals that only received brain injections, LB pathology formed in the brain as well as in the gut.
Takeaway – This research further confirms that the gut and brain are intimately linked in PD.
LRP10 genetic variants in familial Parkinson’s disease and dementia with Lewy bodies: A genomewide linkage and sequencing study (LBA6 – Mandemakers W, et al)
Currently there are a few genes known to be linked to development of PD. Most cases of PD however, (even those with a family history) do not harbor one of the identified genes. An Italian family with 10 affected family members who did not carry any of the known gene mutations was investigated. Mutations in a gene encoding the protein LDL receptor related protein 10 (LRP10) was identified as a new genetic causes of parkinsonism in these patients.
Takeaway – By identifying new genes that cause PD, new treatments can be developed to counteract the effects of the genetic mutation. In addition, knowing which gene mutations cause PD can help explain the underlying mechanisms that cause PD in everyone, even those without that particular mutation.
Safety, tolerability and pharmacokinetics of oral venglustat in Parkinson’s disease patients with a GBA mutation (LBA 21 – Peterschmitt MJ et al)
Mutations in glucocerebrosidase (GBA) are associated with an increased risk of PD. This research presents the results of Part 1 of a phase 2 trial investigating the use of venglustat in PD patient who specifically harbor a mutation in glucocerebrosidase (GBA). Venglustat is a small molecule which is able to cross the blood brain barrier and counteract the effects of the mutated GBA in the brain. The study showed that venglustat was safe and tolerated at all the doses used in the trial. Part 2 of this trial is now underway which will look at whether the medication is effective.
Takeaway – This is one of the first trials in PD which is recruiting only patients with a particular genetic mutation. This type of approach suggests that in the future different types of PD patients may receive different treatments, which is often referred to as “personalized medicine”.