A Mouse Model for Mental Disorders and Epilepsy


Current State of the Art

The Neuregulin/ErbB4 signaling pathway is involved in GABAergic neurotransmission, an important inhibitory neurotransmission that regulates several processes in the central nervous system including muscle tone. Aberrant GABAergic function has been implicated in Schizophrenia, Schizo-affective disorder and in Epilepsy. Clinically overlap has been observed in the development of Schizophrenia, Schizo-affective Disorder and Epilepsy. In some cases treatments for one disorder can cause symptoms of the other. This implies common pathways intertwine in the development of these diseases, implying that therapies can be designed to treat one or all disease states. Further, the Neuregulin/ErbB4 pathway is dependent on down-regulation of AMPA signaling, an anti-epileptic target, to function properly.


Abbott Laboratories, Cephalon, GlaxoSmithKline, Johnson & Johnson, Novartis AG, Pfizer, Sanofi-Aventis SA, Shire, and UCB Pharma contributes to the antiepileptic market which generated $12 billion in 2008. Anti-epileptic drugs including Lyrica and Neurontin (Pfizer), Topamax (J&J) and Keppra (UCB Pharma) comprise ~65% of the total 2008 market.


Schizophrenia affects ~ 1.1% of the adult population in the U.S. The global schizophrenia market was valued at $15.9 billion in 2008 which is expected to reach $17.2 billion by 2015. Therapeutics for patients suffering from Schizophrenia include Fanapt (iloperidone) from Novartis and Zyprexia Relprevv (olanzapine) from Eli Lilly.


Disadvantages with the Current Art

Mouse models available for studies in Schizophrenia, Schizo-affective disorder and Epilepsy include those that manipulate specific candidate genes, those thought to be causative of the disorder. In some cases these models only reveal discreet parts of the disease etiology or progression and do not represent the entirety of the symptoms. The most useful appear to be those that chemically and/or surgically manipulate the animal model to mimic the disorders. Although fruitful for therapeutic discoveries these cannot always be used to identify therapeutics that can treat a patient with an underlying genetic disorder.


Advantages of the Invention

Dr. Lin Mei and co-workers have developed a mouse model system where Neuregulin1/ErbB4 function is disrupted specifically in parvalbumin-positive synapses. PV-positive cells represent GABAergic interneurons responsible for the neurological output of pyramidal cells. Pyramidal neurons are the primary and most numerous excitation units of the mammalian prefrontal cortex and the corticospinal tract. This suggests that pyramidal cells play important roles in advanced cognitive functions and muscle tone. Mice in this model system displayed symptoms of hyperactivity, impaired working memory and deficits in prepulse inhibition, similar to other models for Schizophrenia.


Patent Status:


Inventor:  Lin Mei, PhD


Case Number: GHSU 2010-021 


Patent Information:
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For Information, Contact:
Augusta University
Lin Mei
Wen-Cheng Xiong
Drug Discovery
Drug Testing
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