Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial

  title={Safety and immunogenicity of the $\alpha$-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial},
  author={Dieter Volc and Werner Poewe and Alexandra Kutzelnigg and Petra Lührs and Caroline Thun-Hohenstein and Achim Schneeberger and Gergana Galabova and Nour K Majbour and Nishant N Vaikath and Omar M. A. El‐Agnaf and Dorian Winter and Eva Mihailovska and Andreas Mairhofer and Carsten Schwenke and G{\"u}nther Staffler and Rossella Medori},
  journal={The Lancet Neurology},

Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson’s Disease: A Randomized, Placebo-Controlled, Phase 1 Study

The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials

A comprehensive comparison between experimental and clinical studies in Aβ and αSyn immunotherapy is provided and the possible reasons for the disconnection in their outcomes are determined.

Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance

PD03 and Anle138b can selectively target oligomeric α-synuclein, resulting in attenuation of neurodegeneration in the PLP-α-syn mice, and both approaches are potential therapies that should be developed further for disease modification in α- synucleinopathies.

Slowing Parkinson’s Disease Progression with Vaccination and Other Immunotherapies

The latest disease-modifying treatment options being investigated in PD are active and passive immunization against α-synuclein, which aggregates and is the primary component of Lewy bodies, the histopathological hallmark of PD.

Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease

The various approaches that are being investigated to prevent and mitigate α-synuclein toxicity in PD are discussed, including clearing its pathologic aggregates from the brain using immunization strategies, inhibiting its misfolding and aggregation, reducing its expression level, enhancing cellular clearance mechanisms, and targeting other proteins associated with or implicated in PD that contribute to α-Syn toxicity.

Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies

Diverse approaches include removal of aggregated asyn with passive or active immunization or by expression of vectorized antibodies, modulating kinetics of misfolding with small molecule anti-aggregants, lowering asyn gene expression by antisense oligonucleotides or inhibitory RNA, and pharmacological activation of asyn degradation pathways.

Disease-Associated α-Synuclein Aggregates as Biomarkers of Parkinson Disease Clinical Stage.

It is shown that combining SAA and ELISA assays is more promising diagnostic tool than SAA alone, providing information about the disease stage by correlating with clinical measures of disease severity.

Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

The mechanisms underlying the interaction between α-synuclein and the immune system of Parkinson’s disease are discussed, which can guide the development of associated therapeutic strategies in the future.

Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies

The logical points for gene therapy to intervene in α- Syn-mediated disease are discussed and the preclinical body of work where gene therapy has been used, or could conceptually be used, to ameliorate α-Syn induced neurotoxicity is reviewed.



Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–&agr;-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial

Single and multiple doses of PRX002 were generally safe and well tolerated and resulted in robust binding of peripheral &agr;-synuclein and dose-dependent increases ofPRX002 in cerebrospinal fluid, reaching cerebro Spinal fluid concentrations that may be expected to engage extracellular aggregated aggregated synuclein in the brain.

Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease

The combination of CSF o-/t- α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls and correlated significantly with the severity of PD motor symptoms.

Reducing C-Terminal-Truncated Alpha-Synuclein by Immunotherapy Attenuates Neurodegeneration and Propagation in Parkinson's Disease-Like Models

It is demonstrated that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease.

Next-generation active immunization approach for synucleinopathies: implications for Parkinson’s disease clinical trials

A large library of peptides that mimic the C-terminus region of α-syn were screened and a novel set of AFF that identified α- syn oligomers were discovered, which supported the efficacy of this novel active vaccination approach for synucleinopathies.

Role of α-synuclein in inducing innate and adaptive immunity in Parkinson disease.

The role of α-syn and modified forms of this protein in the initiation of innate and adaptive immune responses is examined and may reveal novel targets for neuroprotective interventions.

Parkinson disease

One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.