New studies shed light on the potential role of monoclonal antibodies in migraine prophylaxis and in Parkinson disease and on a common genetic pathway shared by PD and autoimmune diseases.
New studies shed light on the potential role of monoclonal antibodies in migraine prophylaxis and in Parkinson disease (PD) and on a common genetic pathway shared by PD and autoimmune diseases.
Study 1: American Headache Society Annual Scientific Meeting 2017. Abstracts IOR-12LB, PS88-LB, and PS89-LB. All presented June 10, 2017.
Study 2: Witoelar A, et al. Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases. JAMA Neurol. Published online June 5, 2017. doi:10.1001/jamaneurol.2017.0469
Study 3: International Congress of Parkinson's Disease and Movement Disorders 2017. Presented by Joseph Jankovic, MD, on June 8, 2017.
.Adults with episodic or chronic migraine can find relief with anti-CGRP treatments.
.CGRP levels increase during episodic and chronic migraine, and cause pain and disability. Treatment targeting the CGRP pathway can be delivered either IV intravenously or SQ to reduce migraine days.
.Galcanezumab significantly reduced monthly migraine headache days compared to placebo in two phase 3 clinical trials of more than 1700 patients with episodic migraine. Other anti-CGRP drugs that showed clinical benefits in phase 3 trials include fremanezumab, eptinezumab, and erenumab.
Clinical Implication: CGRP monoclonal antibodies are the first mechanism-based preventive treatment developed specifically for migraine and appear to prevent migraine attacks from actually happening.
Source: American Headache Society Annual Scientific Meeting 2017. Abstracts IOR-12LB, PS88-LB, and PS89-LB. All presented June 10, 2017.
.A common genetic pathway between Parkinson disease and autoimmune diseases suggests that the immune system influences PD pathogenesis.
.Analyses of existing data sets from genome-wide association studies in PD and 7 autoimmune disorders (T1D, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and MS) identified 17 novel loci with overlap between PD and autoimmune diseases. There was a considerable genetic overlap between PD and the autoimmune diseases T1D, Crohn’s disease, and rheumatoid arthritis.
Clinical Implication: These novel mechanistic insights into PD and autoimmune diseases identify a common genetic pathway that may have implications for future therapeutic trials involving anti-inflammatory agents.
Source: Witoelar A, et al. Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases. JAMA Neurol. Published online June 5, 2017. doi:10.1001/jamaneurol.2017.0469
.An investigational monoclonal antibody may inhibit cell-to-cell transmission of alpha-synuclein and modify disease progression in PD. Alpha-synuclein is a protein found in neurons and other cells that is a major component of pathology that characterizes several neurodegenerative disorders, including PD.
.In a phase 1b double-blind, placebo-controlled, multiple-ascending dose study, 80 patients with PD were randomized into 6 escalating dose cohorts to receive the drug PRX002 or placebo. The patients received 3 monthly doses by IV infusion once every 28 days of the humanized IgG1 monoclonal antibody or placebo for 6 months, and were observed for 3 months.
.The drug was well tolerated and showed a rapid dose- and time-dependent reduction of alpha-synuclein levels of up to 97% after a single dose. This result was consistent after 2 additional monthly doses. No serious or severe treatment-emergent adverse events were reported. No dose-limiting toxicities were observed.
Clinical Implication: The new drug represents a promising investigational approach as a disease-modifying immunotherapy designed to target the toxic form of alpha-synuclein that accumulates in PD. A Phase 2 clinical trial will assess how targeting alpha-synuclein may translate into a clinically meaningful delay of disease progression.
Source:International Congress of Parkinson's Disease and Movement Disorders 2017. Presented by Joseph Jankovic, MD, on June 8, 2017.