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Johnson & Johnson : Janssen Neuroscientists And Colleagues Discuss Role Of Mitochondrial Dysfunction In Neuropsychiatric Disorders In Nature Reviews Article

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04/25/2012 | 06:19pm CEST

Article Points to Major Role Mitochondrial Function May Play in Development of Depression and Bipolar Disorder; Calls for New Treatment Approaches, More Efficient Drug-Development

TITUSVILLE, N.J. - April 24, 2012 - Janssen Research & Development, LLC announced today the publication of an article that reviews the growing evidence that impaired mitochondrial function may play a major role in mood and psychotic disorders.  The review discusses recent data from a wide array of human and animal studies that strongly support the theory that impaired mitochondrial function might disrupt neural plasticity pathways and reduce cellular resilience.  These changes may, in turn, promote the development or progression of mood disorders such as major depression and bipolar disorder (BPD), as well as other psychiatric disorders for which the evidence is more limited, such as autism and schizophrenia.  The article, "Impaired mitochondrial function in psychiatric disorders," is published in the May 2012 issue of NATURE REVIEWS/Neuroscience.

The studies discussed in the review highlight the high incidence of psychiatric illness in many diseases where mitochondrial dysfunction or genetic mitochondrial defects are present.  Further, the studies suggest that 'healthy' mitochondrial function may be a key regulator of synaptic strength and cellular resilience in neuronal circuits that mediate complex, high-order brain functions such as cognition, affect, perception, and behavior. 

"Unlocking the mysteries of brain function is fundamental to addressing the health and wellness of people who suffer from disorders like depression, bipolar disorder, and autism," said Husseini K. Manji, M.D., Global Therapeutic Area Head for Neuroscience, Janssen Research & Development, LLC and lead author of the review.  "In elucidating the role of mitochondrial function in the development and progression of these diseases, we are uncovering potential new avenues for their treatment.  Our goal is to advance additional research and the development of new and novel therapeutics for these complex disorders."

To help advance the development of such novel therapies, the authors call for increased research into mitochondrial dysfunction, and stress the need for new strategies in the development of truly novel treatments for highly disabling psychiatric illnesses.  In particular, they advocate the testing of compounds with improved central nervous system (CNS) penetration, as well as compounds other than simple antioxidants. 

Because mitochondria play a broad and fundamental role in cellular processes, the development of novel therapeutics that specifically target mitochondria might be considered particularly challenging, given their potential CNS-specific effects.  Thus, the authors also propose an innovative and potentially more efficient approach to drug development: one in which the smallest common denominator is targeted as the treatment; subsequent efforts would be aimed at scaling up treatments to yield benefits that are more broadly applicable across a range of diseases sharing underlying origins.  In the context of the review, disorders for which either the primary defect occurs in the mitochondria or where there is strong evidence that mitochondria play a key role in disease pathology would represent the most likely targets for treatment success.  If successful, this strategy could potentially benefit an entire family of disorders associated with mitochondrial dysfunction in an efficient, cost-effective way.

The complete text of the review article, "Impaired mitochondrial function in psychiatric disorders," is available at:   http://www.nature.com/nrn/journal/v13/n5/full/nrn3229.html?WT.ec_id=NRN-

About Mitochondria and Psychiatric Disorders
Mitochondria are specialized sub-units of cells that play a pivotal role in cellular energy metabolism; they are also involved in the metabolism of amino acids, lipids, and steroids, the modulation of cellular calcium levels, the production of free radicals, and the regulation of cell death.[1-5]  In the brain, mitochondria are essential to neurotransmission, to the regulation of synaptic activity, learning, and memory,[6-9] to short- and long-term neuronal plasticity, to cellular resilience to stress, and to behavioral adaptation.  Dysfunction in these metabolic processes is implicated in a wide variety of diseases, including psychiatric disorders.

Healthy Minds
Janssen's work in mental health is part of its Healthy Minds initiative, which builds on Janssen's longstanding legacy of achievement in advancing neuroscience research.  The company's work in this area dates back to the 1950's, and to the discovery and development by Dr. Paul Janssen of one of the first breakthrough treatments for schizophrenia.  Indeed, Janssen Research & Development, LLC is named for Dr. Paul Janssen-known as one of the 20th century's most gifted and passionate physicians and pharmaceutical researchers.  Over the last half century, Janssen has discovered, developed and launched many innovative treatments for brain and central nervous system (CNS) conditions and remains firmly committed to neuroscience.  Janssen commits more than $12 million annually to public and professional education about mental illness and brain disorders, sponsorships and philanthropy in the field of neuroscience and mental health. 

Janssen Research & Development, LLC
Janssen Research & Development, LLC is headquartered in Raritan, N.J., and has facilities throughout Europe, the United States, and Asia.  The company is actively involved in drug discovery and development to address key, unmet medical needs worldwide across a variety of therapeutic areas, including Cardiovascular and Metabolism, Central Nervous System, Immunology, Oncology, and Virology to address unmet medical needs worldwide.  More information can be found at http://www.janssenrnd.com/.



1.  Mattson, M. P., Gleichmann, M. & Cheng, A. Mitochondria in neuroplasticity and neurological disorders. Neuron 60, 748-766 (2008).
2.  Gleichmann, M. & Mattson, M. P. Neuronal calcium homeostasis and dysregulation. Antioxid. Redox. Signal. 14, 1261-1273 (2011).
3.  MacAskill, A. F., Atkin, T. A. & Kittler, J. T. Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. Eur. J. Neurosci. 32, 231-240 (2010).
4.  Jonas, E. BCL-xL regulates synaptic plasticity. Mol. Interv. 6, 208-222 (2006).
5.  Jonas, E. A. Molecular participants in mitochondrial cell death channel formation during neuronal ischemia. Exp. Neurol. 218, 203-212 (2009).
6.  Hu, D., Serrano, F., Oury, T. D. & Klann, E. Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase. J. Neurosci. 26, 3933-3941 (2006).
7.  Thiels, E. et al. Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase. J. Neurosci. 20, 7631-7639 (2000).
8.  Li, Z. et al. Caspase

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Financials ($)
Sales 2016 72 080 M
EBIT 2016 21 940 M
Net income 2016 16 371 M
Finance 2016 19 430 M
Yield 2016 2,74%
P/E ratio 2016 19,38
P/E ratio 2017 17,09
EV / Sales 2016 4,08x
EV / Sales 2017 3,80x
Capitalization 313 422 M
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Average target price 126 $
Spread / Average Target 10%
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Alex Gorsky Chairman & Chief Executive Officer
Dominic J. Caruso Chief Financial Officer & Vice President
Paulus Stoffels Chief Scientific Officer
Susan L. Lindquist Independent Director
Charles O. Prince Independent Director
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