Research Highlights

Credit: Philip Patenall/Macmillan Publishers Limited PARKINSON DISEASE Prediction of cognitive decline in PD Structural and microstructural nucleus basalis of Meynert could be changes in the nucleus basalis of underlying cognitive impairment in In the news Meynert are associated with and patients with PD,” explains Politis. predictive of cognitive impairment “We chose MRI because we wanted to Stars of neurology meet in Parkinson disease (PD), according use a common imaging technique that at AAN 2018 to a recent study. The work identifies is accessible to patients in the clinic.” a clinically applicable marker that The researchers analysed data Los Angeles provided the venue for this year’s American could help with early identification from the Parkinson’s Progression Academy of Neurology Annual Meeting (AAN 2018). The and treatment of patients at risk. Markers Initiative database, including programme featured presentations from big names and rising Cognitive impairment is common 304 patients with PD and 167 healthy stars in the neurology field and highlighted an array of in PD, but predictive markers of controls. T1-weighted MRI data were promising new therapies. cognitive decline have not been used to assess grey matter volume, and Advances in migraine treatment came under the identified. Loss of cholinergic diffusion tensor imaging data were used spotlight at AAN 2018, with a particular focus on therapies function has previously been to assess diffusivity in white matter. that target calcitonin gene-related peptide (CGRP) — a linked to dementia and cognitive Cross-sectional analysis revealed neurotransmitter that is released from sensory neurons impairment, so in their new study, that in patients with PD, cognitive during migraine attacks. Joel Trugman reported on ACHIEVE Marios Politis and colleagues focused impairment was associated with I, a phase II trial of the CGRP receptor antagonist ubrogepant their attention on the cholinergic reduced grey matter volume and for the acute treatment of migraine. The drug provided nucleus basalis of Meynert. increased white matter diffusivity in significant benefits with regard to pain and “Using MRI, we wanted the nucleus basalis of Meynert. migraine-associated symptoms. to see whether structural and A longitudinal analysis of MRI data, Monoclonal antibodies against CGRP are also proving microstructural changes in the collected over 36 months from patients beneficial in individuals with migraine. Uwe Reuter presented evidence that erenumab can provide pain relief in patients with difficult-to-treat migraine. In addition, Richard Lipton PARKINSON DISEASE reported that patients with chronic migraine experienced a significant reduction in monthly migraine days in response to treatment with eptinezumab (8.2-day reduction, compared Designer exosomes with 5.6 days in placebo-treated patients). Antisense oligonucleotide (ASO) therapy received top billing at AAN 2018. Sarah Tabrizi reported on a phase I/IIa trial of alleviate neurotoxicity

IONIS-HTTRx in patients with early-stage Huntington disease. Investigators have developed a based on implanted mammalian The treatment was well tolerated and produced dose-dependent cell system that can mass-produce designer cells,” says Martin reductions in levels of mutant huntingtin (mHTT) in the exosomes to shuttle high levels Fussenegger, corresponding author cerebrospinal fluid. Although the trial was not designed to of therapeutic RNA across the on the new study. “However, outputs measure efficacy, mHTT lowering was found to correlate with blood–brain barrier and into target of the cells have been limited to improvements in motor scores and cognitive function. neurons. Implantation of these cells proteins, and therefore we thought Richard Finkel provided an update on emerging therapies alleviated neuronal death there may be some synergistic for spinal muscular atrophy (SMA), including the and neuroinflammation in a opportunity of using these two ideas: FDA-approved ASO nusinersen, and gene-replacement mouse model of Parkinson disease secreting designer exosomes from strategies. Small-molecule drugs could also have a starring (PD), suggesting that this system implanted cells.” role in the treatment of SMA in the future. Giovanni Baranelli presents a novel strategy for The investigators generated cells that presented data from the FIREFISH Part 1 trial, which tested the treatment of neurological were able to produce neuron-targeted the small molecule RG7916 in babies with SMA type 2. The disorders. exosomes over a prolonged time frame drug was found to increase blood levels of survival motor Exosomes are small secreted and could be implanted into living neuron protein (SMN) by modulating SMN2 gene splicing. vesicles that mediate communication animals. The cells were genetically between cells. These structures Trials are now underway to determine the clinical efficacy engineered to boost the efficiency have gained increasing attention of exosome delivery. of RG7916. as a method of delivering targeted The researchers tested the Summarizing the recent therapeutic advances in SMA and therapies, but their short half-life ability of their system to alleviate other neuromuscular diseases in the final plenary session of and inefficiency in cargo delivery neuroinflammation, an important the meeting, Ericka Simpson concluded that neuromuscular has limited their use. contributing factor in PD. Cells were medicine is reaching a “tipping point”, catalysed by a “perfect “Our laboratory has been generated that packaged RNA encoding storm of collaboration”. focusing on next-generation therapy the antioxidant enzyme catalase, which is Heather Wood

316 | JUNE 2018 | volume 14 www.nature.com/nrneurol