by Viktoria Papp
Each month the eanNews editorial team reviews the scientific press for recently published papers of outstanding interest to neurologists. Below we present our selection for February 2025.
1) An Acetylcholine M1 Receptor–Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment – A Phase 2 Randomized Clinical Trial | JAMA Neurology
Patients with Parkinson’s disease (PD) have increased risk of developing cognitive impairment and tendency to fall. Emerging evidence suggests that both gait and cognitive impairment are linked to the disruption of cholinergic neurotransmission. In this phase 2 randomised double-blind placebo-controlled crossover trial, TAK-071, an acetylcholine M1 receptor positive allosteric modulator was tested in 54 PD patients with fall history and cognitive symptoms in order to evaluate the drug’s safety and efficacy. The results found no difference in the primary outcome regarding gait impairment between TAK-071 and the placebo. Cognitive impairment was the secondary outcome where TAK-071 improved the cognitive composite score, especially the domains of attention and executive function compared to placebo. In general, the drug was well-tolerated. There is a need for further investigations in larger patient populations to establish a better understanding of the benefits of TAK-071 in PD.
2) Novel Meningoencephalomyelitis Associated With Vimentin IgG Autoantibodies | JAMA Neurology
The spectrum of autoimmune CNS disorders is expanding and this case series reveals a rare novel astrocytopathy where autoimmune IgG antibodies target vimentin, a type III intermediate filament protein which is important for cellular structure and integrity. B-cells from CSF of the 2 index patients with suspected autoimmune encephalomyelitis were analysed by using single-cell immune repertoire and transcriptome sequencing to identify astrocyte-reactive autoantibodies and targeted antigen and led to the discovery of vimentin IgG antibodies. A comprehensive screening of 1669 CSF samples from patients with uncharacterised neuroimmune diseases revealed the presence of vimentin IgG autoantibodies in 12 additional patients with similar characteristics to the index patients. The common clinical features of these 14 patients are relapsing disease courses and symptoms predominantly from the cerebellum, brainstem, and corticospinal tract. All patients had intrathecal immunoglobulin synthesis and elevated CSF cells and protein. Magnetic resonance imaging showed bilateral lesions on the corticospinal tract. Large multicentre cohort studies are needed to determine the incidence and the spectrum of clinical features of this condition.
3) Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy A Randomized Clinical Trial With Open-Label Extension | JAMA Neurology
Hereditary transthyretin amyloidosis (hATTR) is an inherited progressive life‐threatening multiorgan disease caused by mutations in the transthyretin gene leading to deposition of amyloid in different organs. Patisiran, an RNA interference therapeutic inhibiting the hepatic transthyretin protein synthesis, is approved to treat polyneuropathy caused by hATTR amyloidosis. Here, the authors reported on the long-term safety and efficacy data from open-label extension (OLE) of the APOLLO randomised clinical trial and phase 2 OLE study. In the original APOLLO study, patients were randomised either to patisiran or placebo while during the 5-year extension all patients were treated with patisiran 0.3mg/kg, intravenously once every 3 weeks. Pooled data of the 138 patients who also completed the 5-year extension study showed that most patients who started in the phase 2 OLE and APOLLO patisiran groups had stable or improved polyneuropathy disability score and almost all patients maintained their ability to walk at the end of the 5-year extension study. Those in the APOLLO placebo group had disease progression during placebo treatment which decreased over 5 years of patisiran treatment in the extension study. Body mass index increased as sign of better nutrition status. Life quality and survival improved significantly with patisiran treatment. However, patients did not recover functions that they lost before starting patisiran treatment, which highlights the importance of early diagnosis and treatment initiation.
