Probiodrug : Top-Line Results of the First Clinical Study of PQ912 for Treatment of Alzheimer’s Disease

November 14, 2011 - Phase 1 Study of the First Glutaminyl Cyclase (QC) Inhibitor, Which Blocks Formation of Highly Neurotoxic pyroGlu Aβ Variants, Shows that PQ912 is Well Tolerated With Therapeutically-Relevant Levels in Blood and Cerebrospinal Fluid –

Probiodrug AG (Probiodrug), a biotech company developing products for the treatment of neurodegenerative and inflammatory diseases, with a particular focus on Alzheimer's disease (AD), today announced top-line results of its Phase 1 single (SAD) and multiple ascending dose (MAD) study of PQ912 in healthy volunteers. PQ912 is a glutaminyl cyclase (QC) inhibitor for the treatment of AD and it is the first QC inhibitor to enter clinical development.

The Phase 1 trial, conducted in Switzerland, demonstrated that PQ912 is safe and well tolerated after oral dosing. Dose-proportional pharmacokinetics and a strong pharmacokinetic and pharmacodynamic relationship based on QC inhibition were observed in plasma and cerebrospinal fluid. The combined SAD/MAD study involved 100 volunteers in a blinded, placebo controlled randomized trial.

PQ912 is a small molecule that targets QC, an enzyme that catalyzes the formation pyroGlu amyloid-beta (Aβ) a highly toxic Aβ variant that is involved in the development and progression of AD. AD is a neurodegenerative disease characterized by deposits of extracellular Aβ plaques in the brain, intraneuronal tangles and cerebral neuronal loss. QC inhibitors address a major pathology associated with AD by inhibiting the formation of Aβ variants which lead to the assembly of highly neurotoxic Aβ-oligomers... Probiodrug's Press Release -

Astellas and RIKEN : Collaborative Research Launched to Explore Novel Drug Targets for Alzheimer’s Disease

November 8, 2011 - RIKEN Brain Science Institute and Astellas Pharma Form Strategic Alliance for New Drug Discovery -

RIKEN, Japan (President: Ryoji Noyori) and Astellas Pharma Inc. (President: Yoshihiko Hatanaka, hereafter called “Astellas”) have signed a five year joint research agreement for the purpose of “deciphering the pathogenic mechanism for and identifying novel drug targets for Alzheimer’s disease”. With the goal of conquering the social burdens of Alzheimer’s disease, synergies between the fundamental research function of RIKEN Brain Science Institute (RIKEN BSI, Director: Susumu Tonegawa) and drug discovery capabilities of Astellas will be leveraged to develop revolutionary new drugs.

1. Background

The number of patients within Japan suffering from Alzheimer’s disease and other forms of dementia is expected to rise along with the aging of the Japanese society and reach 3.25 million by the year 2020 (Source: “Everyone’s Mental Health” of the Ministry of Health, Labor and Welfare). About half of patients with dementia suffer from Alzheimer’s disease, and the burden upon their families and society is heavy. Consequently, the conquering of Alzheimer’s disease at an early stage is an important issue for Japan as a medically advanced country. However at the current time there are no fundamental treatments or preventative measures that have been established, and there are only symptomatic treatments. In order to establish fundamental treatments, it is critical to fully understand the pathogenic mechanisms of the disease and to translate the findings on important mechanisms into discovery of novel drugs for the disease.

Laboratory for Proteolytic Neuroscience at the RIKEN BSI conducts research designed to acquire fundamental knowledge for mechanisms of proteolysis responsible for pathological cascade in neurodegenerative diseases that can be used in the diagnosis, prevention, and treatment of patients with neurodegenerative disorders. In particular, the top priority given to Alzheimer’s disease has led to the acquisition of new information on the important causative agent (amyloid beta peptide) in July 2011... [PDF] Astellas Pharma's Press Release - RIKEN's Press Release -