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As Michael J. Fox Returns to Primetime, His Research Foundation Urgently Pursues the Cure for Parkinson’s

Last month, Michael J. Fox returned to television as the star of his own sitcom after more than two decades living with Parkinson’s disease. Fox’s decision to return to primetime has injected Parkinson’s into the national conversation — a conversation already transformed by The Michael J. Fox Foundation for Parkinson’s Research (MJFF), which the actor launched in 2000 with the exclusive goal of funding research to speed a cure for the disease.

Elevated Levels of Copper in Amyloid Plaques Associated with Neurodegeneration in Mouse Models of AD

Metals such as iron, copper, and zinc are important for many biological processes. In recent years, studies have shown that these nutritionally-essential metals are elevated in human Alzheimer’s disease (AD) brains and some animal models of AD. Scientists are now exploring whether these metals are causing the neurodegeneration seen in AD or are indicative of other ongoing pathologic processes.

In a new study, investigators used synchrotron x-ray fluorescence microscopy to image metal ions in the brain, focusing on the amyloid plaques that are the hallmark of AD. They found that, in two AD mouse models that exhibit neurodegeneration, the plaques contained about 25% more copper than an AD mouse model that shows little neurodegeneration. Looking at other metals, they found that none of the mouse models had significant increases in iron and very little increases in zinc. Metal content was not related to the age of the plaque. The study is reported in the current issue of Biomedical Spectroscopy and Imaging.

“Since excess copper should not be ‘free’ in the brain to bind to the plaques, these data suggest that the cellular control of copper is altered in AD, which may lead to toxic reactions between free copper ions and neurons,” comments lead investigator Lisa M. Miller, PhD, a biophysical chemist in the Photon Sciences Directorate at Brookhaven National Laboratory. In previous work, Dr. Miller’s group found very high levels of copper in human AD plaques.

Since elevated iron in the AD brain is well documented in both human brains and AD mouse models, the researchers measured iron content in the cortex of all three mouse models. They found that iron content was doubled in all AD mouse model cortices compared to controls, whether or not the models showed neurodegeneration. Upon further investigation, spectroscopic data revealed that the excess iron was present in the ferric (oxidized) state and consistent with the iron storage protein ferritin. “The increase in iron may be a reflection of changes in metalloprotein content and metal storage within the brain that is not well understood,” says Dr. Miller.

Nevertheless, since iron in ferromagnetic and detectable through MRI, Dr. Miller suggests that in the future iron may be used as a biomarker for AD at early stages of disease, even before plaques are formed.

Source: Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer’s disease that exhibit neurodegeneration [Biomedical Spectroscopy and Imaging]

Source: EurekAlert!

Lilly Acquires Novel Tau Tangle Diagnostic Program to Bolster Alzheimer’s Disease Research and Development

Eli Lilly and Company (NYSE: LLY) recently announced it has acquired two investigational positron emission tomography (PET) tracers from Siemens Medical Solutions USA, Inc. The tracers are intended to image tau (or neurofibrillary) tangles in the brain, one of two known hallmarks of Alzheimer’s disease. Based on studies of samples obtained at autopsy, the amount and location of tau tangles in an Alzheimer’s disease patient’s brain is thought to correlate with the severity of the disease. There are currently no approved diagnostics to detect tau tangles in living patients, creating challenges for scientists working to understand the progression of the disease and how therapies may impact it.

Lilly will initially focus on incorporating this new technology into its anti-amyloid and anti-tau research and development (R&D) programs. Use of a tau tangle tracer could enable tailoring and early identification of at-risk patients, as well as potentially provide a marker for treatment response. Lilly also has the option to commercialize the tracers. The tracers will be developed and validated by a team at Avid Radiopharmaceuticals, Lilly’s wholly owned subsidiary focused on molecular imaging. Financial terms of the deal are not being disclosed.

“The acquisition of these tau tangle tracers builds on our 25-year commitment of investing in Alzheimer’s disease research and development to bring new medicines to patients facing the terrible consequences of Alzheimer’s disease,” said Jan M. Lundberg, Ph.D., executive vice president, science and technology, and president, Lilly Research Laboratories. “We are hopeful that this technology will both enhance our understanding of tau and its role in Alzheimer’s disease, and contribute to the development of our anti-amyloid and anti-tau based therapies to treat this disease.”

“PET imaging is a valuable tool in the fight against Alzheimer’s disease, and Siemens is committed to helping fight this growing threat to our aging population,” said James Williams, CEO, Siemens Molecular Imaging business unit. “Lilly’s continued development of these tau PET tracers combined with Siemens’ ongoing investment in innovative PET imaging solutions is another great example of how Siemens is collaborating with pharmaceutical companies in an effort to provide new hope to patients and their families.”

There are two defining pathologies linked to the development of Alzheimer’s disease: the accumulation of amyloid-beta protein that forms beta-amyloid plaques outside of neurons, and the accumulation of tau protein that forms tau tangles inside them.The formation of tau tangles is thought to block the transport of nutrients and essential molecules throughout the cell, leading to neurodegeneration, or the progressive loss of structure or function of neurons. The formation of tau tangles mostly occurs after beta-amyloid plaques have developed, but unlike beta-amyloid plaques the evolution of tau tangle pathology is believed to closely mirror cognitive decline.

Scientists theorize that both beta-amyloid plaques and tau tangles are required for the development of Alzheimer’s disease, with the accumulation of amyloid beta representing the early trigger that initiates the disease process and tau tangles playing a secondary but critical role in the process of neuronal toxicity and death. For this reason, Lilly has established R&D programs to explore both the amyloid and tau hypotheses. Today’s acquisition will inform and help progress Lilly’s multiple approaches to treating Alzheimer’s disease, with the goal of speeding innovation to patients worldwide.

Source: Eli Lilly

Orion Bionetworks: Developing Predictive Models to Power the Search for Cures

Today we announce the launch of Orion Bionetworks, a multi-institution cooperative non-profit alliance that is unlocking the power of shared data and predictive modeling to help transform our understanding of diseases such as multiple sclerosis (MS) and accelerate the search for cures. Alliance partners include leading organizations in patient care, computational modeling, translational research, and patient advocacy: Accelerated Cure Project for Multiple Sclerosis, the Institute for Neurosciences at Brigham and Women’s Hospital, GNS Healthcare, MetaCell, and PatientsLikeMe. Janssen Research & Development, LLC, a New Jersey-based pharmaceutical company, has provided a $5.4 million scientific sponsorship as part of its Healthy Minds program for the initial phase of this effort.

Orion Bionetworks has been established as a program of the Marin Community Foundation. Its President & CEO, Thomas Peters, Ph.D., hailed the formation of the new alliance. “We are enormously proud to welcome Orion Bionetworks within the Foundation,” said Peters. “We are confident that this blend of expertise and creativity will lead to significant scientific success.”

Key supporting partners include One Mind for Research, Morrison & Foerster, Recombinant Data, and Weber Shandwick.

A Unique Cooperative Alliance

Through Orion Bionetworks, alliance partners contribute to a communal body of knowledge in the pursuit of better disease understanding, prevention and treatment, and gain access to state-of-the-art analytical tools, technologies and inter-disciplinary expertise.

Initially, Orion Bionetworks will focus on integrating clinical, biomarker and imaging data with rich real-world patient data from existing, independent databases of over 7,000 people with MS into a causal computational disease model.

PatientsLikeMe Co-Founder and Chairman Jamie Heywood said, “This silo-breaking initiative allows data from disparate sources, including our patient network of thousands of individuals who monitor their health and share their MS symptom and treatment information, to be analyzed in a way that will transform future discoveries and maximize the benefit for all.”

Computational Modeling

Computational modeling, or biosimulation, is an emerging research platform that has the potential to transform our understanding of human biology and predict which individual or environmental factors influence the development and progression of disease. Application of sophisticated modeling and simulation technologies for drug discovery and development could help the healthcare industry overcome the current economic and product pipeline challenges it faces in a number of therapeutic areas including neuroscience.

Orion Bionetworks is creating a framework to advance causal disease models by supporting the creation of new computational tools and communities and facilitating their access to integrated, large-scale, diverse biological and clinical data from registries and repositories.

“By bringing together this multidisciplinary group of collaborators and enabling the sharing of integrated clinical and ‘omics data, Orion Bionetworks could help realize the promise of computational modeling in disease research,” said Iya Khalil, Executive Vice President and Co-Founder of GNS Healthcare, one of the alliance members. “Causal models learned directly from data will help us understand the biology of the disease and predict which approach to treatment will work for individual patients. This could accelerate the search for cures.”

Advancing Understanding of Multiple Sclerosis

Orion Bionetworks’ initial focus is multiple sclerosis. MS affects over 2.5 million individuals worldwide. It is an exceedingly complex spectrum of diseases that involves both acute inflammation and chronic, progressive neurodegeneration in the brain and spinal cord. Physicians are challenged with managing patients whose course ranges from mild disease with modest levels of disability to a small number of treatment-refractory cases with profound disability. Currently, no one can predict an individual patient’s course or whether they will respond to a prescribed therapy. Further, while we can suppress the inflammatory component of MS to some extent, there is no treatment for its neurodegenerative component and no treatment that cures a patient. Thus, this unpredictable illness takes a tremendous toll on patients and their families. However, with recent advances in biomedical science and analytic methods, MS is uniquely ready for the new tools of predictive modeling, which can integrate diverse datasets and answer critical questions beyond the reach of individual research efforts.

“The path forward is clear: through Orion Bionetworks, one large dataset of patients can be explored very deeply with all available platforms to create a reference atlas of MS,” said Philip De Jager, MD, PhD, a physician researcher at the Institute for Neurosciences at Brigham and Women’s Hospital. “With such an atlas of MS, we can chart a route forward towards the personalization of MS care and the targeting of MS-related neurodegeneration.”

Additional information on the organization and partnership opportunities is available on the organization’s website, www.orionbionetworks.org.

Source: Business Wire

KineMed, Isis and CHDI Collaborate to Advance Therapeutic Development for Huntington’s Disease and Develop Novel Biomarkers for Pre-clinical and Clinical Use in Drug Development and Therapeutic Monitoring

KineMed, Inc., Isis Pharmaceuticals Inc. (NASDAQ: ISIS), and CHDI Foundation, Inc., announced today that they are collaborating to utilize KineMed’s translational biomarker platform with Isis’ antisense therapeutic program for Huntington’s disease (HD). This collaboration, which builds on an earlier alliance between CHDI and KineMed to develop companion biomarkers of therapeutic response in HD, will provide Isis access to novel biomarkers for use in the development of an antisense drug to treat HD.

“A pharmacodynamic biomarker could be an important contribution to our clinical development efforts, and we look forward to working with KineMed and CHDI to evaluate KineMed’s biomarker platform in our Huntington’s disease program,” said Frank Bennett, Ph.D., Senior Vice President of Research at Isis.

“This companion biomarker partnership represents personalized medicine in action,” said Patrizia Fanara, Ph.D., Vice President of Neuroscience KineMed. “Our neurodegeneration-specific biomarkers, which provide dynamic measures of axonal transport deficits in degenerating brain cells, predict therapeutic response in neurological and neuromuscular disorders. This is a translational biomarker that could prove crucial to the advancement of disease-modifying treatments. With the Huntington’s disease domain knowledge that CHDI brings and the therapeutic approach that Isis is pioneering, this partnership has the potential to develop biomarkers for specific therapeutics for Huntington’s disease and lead to personalized medicines for Huntington’s patients.”

“There is a critical need to identify appropriate biomarkers to determine target engagement and predict early clinical efficacy for future Huntington’s disease clinical trials,” said Jonathan Bard, Ph.D., Director of Molecular Pharmacology for CHDI Foundation. “Combining Isis’ knowledge of antisense therapies with KineMed’s expertise in developing unique pharmacodynamic biomarkers creates a collaboration with great potential for discovering such tools for Huntington’s disease.”

KineMed’s neurodegeneration biomarker of axonal transport deficit has been recently published in the Journal of Clinical Investigation1 and validated in patients with other neurological disorders.

Source: Business Wire