AstraZeneca Neuroscience IMED has partnered with the Michael J. Fox Foundation for Parkinson’s Research (MJFF) to support research on levodopa-induced dyskinesias (LID), a complication of medicines commonly used to reduce Parkinson’s disease symptoms. Parkinson’s Disease is a chronic degenerative neurological disorder affecting cells in the brain that control body movements. It affects about 1% of the population over 60 years of age. The Neuroscience IMED will apply the $465,000 grant toward preclinical study of a novel nicotinic receptor agonist. If this research and subsequent clinical trials prove successful, AstraZeneca hopes to deliver a medicine that will reduce LID, enabling Parkinson’s disease patients to optimise their treatment with levodopa.
Our collaboration with Trinity College Dublin and Brigham and Women’s Hospital, Cambridge MA, investigates the toxic species of aggregating proteins found in brain samples of patients with Alzheimer’s disease. Using biochemical and in vivo electrophysiological approaches we aim to understand how these proteins interact with neurones to disrupt synaptic communication. The collaboration also supports the development of translational assays to profile key disease proteins in patient cerebrospinal fluid.
In 2017, we entered into an agreement with Takeda for joint development and – if clinical studies are successful – commercialisation of MEDI1341, an ɑ-synuclein antibody with high affinity and selectivity and reduced effector function. Phase I trials started at the end of 2017 to investigate the potential of the compound as a disease-modifying treatment for Parkinson’s disease. AstraZeneca will oversee the Phase I development and Takeda will lead future clinical development activities.
This collaboration with Berg aims to validate novel targets for treatment of Parkinson’s disease identified through Berg’s AI platform known as ‘Interrogative Biology’. The method employs human patient biosamples to identify disease targets, and the goal is to screen AstraZeneca small molecules against specific targets and to follow up hits derived from these screens.
We work closely with Steve Haggarty’s laboratory on pathways related to tauopathies and synapse-opathies such as Fragile X syndrome. We employ human induced pluripotent stem cell models to understand disease mechanisms and also test small molecules for modification of phenotypes. Our ambition is to develop and explore the potential of human inducible pluripotent stem cells (iPS) cell systems and ultimately identify candidate therapeutics for specific disorders.
Building on an existing strategic partnership between AstraZeneca, MedImmune and the University of Cambridge in the UK, the Neuroscience IMED began a 3-year collaboration with leading scientists to advance our understanding and treatment of neurodegenerative disorders such as Parkinson’s Disease, Alzheimer’s Disease and multiple sclerosis. Working with six key investigators (Professors Rubinsztein, Rowe, Barker, Livesey, Spillantini and Franklin), the collaboration aims to drive target selection, biomarker identification and personalised healthcare approaches by studying cell and animal models of proteinopathies, modulating autophagy and examination of the effects of aging on oligodendrocytes. The collaboration is co-directed by the IMED’s Iain Chessell, Keith Tan, Andy Billinton and Mike Perkinton.
The team of ten scientists continues to focus on targets related to neurodegeneration, epilepsy and neurodevelopmental disorders. The team thrives in the academic environment of Tufts with the support of key AstraZeneca scientists on the ground. Highlights from 2017 include providing data sets which led to a critical project transition and the publication of a number of excellent papers in journals such as PNAS, JBC and Nature Medicine.
The Neruoscience IMED has secured a grant from Target ALS in collaboration with two leaders of Amyotrophic lateral sclerosis (ALS), research– Dr Aaron Gitler (Stanford) and Dr James Shorter (Penn). As part of the collaboration, AstraZeneca will screen for modulators of a range of ALS-linked proteins, which have been implicated by genetics and pathology in the disease. Downstream deconvolution will be conducted in the academic labs. Target ALS is a philanthropic venture aiming to catalyze research and find treatments for ALS.
AstraZeneca Neuroscience IMED is partnering with the National Institute on Drug Abuse (NIDA), an arm of the U.S. government’s National Institutes of Health (NIH), to explore the potential of the Neuroscience IMED’s metabotropic glutamate receptor modulators as novel treatments for drug addiction. As part of the collaboration, NIDA will conduct and fund a Phase II trial of AZD8529 in smoking cessation as part of its strategic medications development program with AstraZeneca supplying drug for the study. The AstraZeneca molecule represents a distinct approach from existing treatments and holds potential for preventing relapse and sustaining abstinence from smoking, areas of high unmet need not served by current treatments. The collaboration also involves preclinical work providing critical supporting data for nicotine addiction and will expand to include substance abuse disorders.
Our collaboration with Professor Stephen McMahon investigates the role of inflammatory mediators such as nerve growth factor and tumour necrosis factor, in pathways central to chronic pain states. The work focuses on potential additive or synergistic effects due to interactions between these and other mediators. The studies are helping to elucidate the mechanism of existing clinical candidates and the potential to contribute new targets to the portfolio.
In 2016, we announced a collaboration with Lilly to co-develop MEDI1814, an antibody selective for Aβ42, which is currently in Phase I trials as a potential disease modifying treatment for Alzheimer’s disease. This agreement builds on the existing collaboration related to AZD3293, a BACE inhibitor in two pivotal Phase III trials.
AstraZeneca and Eolas Therapeutics have entered into a worldwide license and partnership agreement on the Eolas Orexin-1 Receptor Antagonist (EORA) program for smoking cessation and other indications. This program has been awarded a Blueprint Neurotherapeutics (BPN) grant from the National Institutes of Health (NIH) that would support development of the program through Phase I clinical trials. The collaboration is a great example of our unique approach to Neuroscience drug discovery and development, partnering to advance the most exciting scientific opportunities in areas of high unmet medical need.