Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: a phase 1 placebo-controlled trial.

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF).

RBD-Protein/Peptide Vaccine UB-612 Elicits Mucosal and Fc-Mediated Antibody Responses against SARS-CoV-2 in Cynomolgus Macaques.

Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein-peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays.

A Randomized First-in-Human Study With UB-312, a UBITh® α-Synuclein Peptide Vaccine.

Background: α-Synuclein (αSyn) is believed to play a central role in Parkinson's disease (PD) neuropathology and is considered a target for disease modification. UB-312 is a synthetic αSyn peptide conjugated to a T helper peptide and is expected to induce antibodies specifically against oligomeric and fibrillar αSyn, making UB-312 a potential immunotherapeutic for synucleopathies.

Objective: To investigate the safety, tolerability, and immunogenicity of UB-312 vaccination in healthy participants and to determine a safe and immunologically optimal dose for the first-in-patient study.

Variant-selective stereopure oligonucleotides protect against pathologies associated with C9orf72-repeat expansion in preclinical models.

A large GC-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal degeneration associated with this expansion arises from a loss of C9orf72 protein, the accumulation of RNA foci, the expression of dipeptide repeat (DPR) proteins, or all these factors. We report the discovery of a new targeting sequence that is common to all C9orf72 transcripts but enables preferential knockdown of repeat-containing transcripts in multiple cellular models and C9BAC transgenic mice.