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Light-off jump response habituation and PPI system for high-throughput testing of non-associative learning and sensorimotor gating in the visual sensory modality |
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Aktogen Ltd. – www.aktogen.com – is a Cambridge University start-up company, founded in 2003 for the discovery of drugs to treat Central Nervous System (CNS) related disorders, such as neurodegenerative disorders, intellectual disability (mental retardation) and neuropsychiatric disorders. The company has been funded to date by private investment, a DTI SMART Award and a European Union research fund. Founding director is Dr. Zoltan Asztalos, who has long standing experience in Drosophila, fruit fly behaviour genetics. Investor-directors are Dr. William Budenberg and Mr. Mike Thilo and the company is supported by an internationally renowned Advisory Board from the fields of business, technology, Drosophila and vertebrate behaviour genetics and drug discovery.
Aktogen has developed a fruit fly based automated cognitive behaviour screening technology, which has already been employed to fulfil a service contract work for the University of Cambridge. The company is currently part of a European Union 7th Framework consortium, GENCODYS (see http://www.gencodys.eu/). The consortium is dedicated to study the functions and dysfunctions of the brain with particular focus on intellectual disability and autism. Although Drosophila CNS disease models are well established for neurodegenerative disorders GENCODYS provides the opportunity for Aktogen to validate its fruit fly behaviour and drug delivery platform for other CNS disorder models, as well.
Currently the company is finishing the development of a high-throughput insect drug delivery system to complement its behaviour paradigms. Furthermore, -- in collaboration with a EU knock-out mouse center, the Institut Clinique de la Souris (ICS), Strasbourg, France, http://www.ics-mci.fr/ – we are developing a Drosophila behaviour test battery that matches many of the tests employed in mouse during drug target (knock-out mouse) and compound tests. The currently planned assays include: motor abilities, pain sensitivity, vision, anxiety related behaviour, learning and memory, sensorimotor gating, circadian activity, social recognition.
In 2010 Aktogen Limited founded Aktogen Hungary, a wholly owned subsidiary in Hungary to accelerate the development of Alzheimer’s and prion Drosophila disease models. Aktogen Hungary operates within the Biological Research Centre (BRC) of the Hungarian Academy of Sciences in Szeged and makes collaboration with reserch groups at the institute.
Drug Target and Drug Candidate Screening Capabilities Aktogen uses the fruit fly to accelerate the discovery of drug targets and potential drugs. Our particular edge is the development of automated systems for fast screening of complex behaviour phenotypes that have relevance for human CNS disorders. Aktogen’s technology allows initial fast screening of potential drug candidates in vivo and furthermore enables it to directly link genetic information to neural conditions.
Although, our first applications are in intellectual disability and neurodegenerative disorders, the technology will be readily adaptable to other CNS conditions such as Parkinsonism, drug abuse, sleep disorders, chronic pain, neuropsychiatric disorders, safety pharmacology, etc. Drosophila show a wide repertoire of behaviour, for example several forms of learning, including habituation. Habituation is a non-associative learning mechanism whereby an initial response wanes with repeated stimulation. Pre-pulse Inhibition (PPI) is a neurological phenomenon in which a weaker pre-stimulus (pre-pulse) inhibits the reaction of an organism to a subsequent strong startling stimulus (pulse).
Habituation and PPI are measures of sensorimotor gating, a process by which irrelevant information is filtered from the environment and brain processes. Habituation and PPI deficits of startle have been identified as features of schizophrenia, although it has been noted in panic disorder, schizotypal personality disorder, obsessivecompulsive disorder, Huntington’s disease, attention deficit hyperactivity disorder, as well. Aktogen developed semiautomated habituation assays and a novel PPI paradigm for high-throughput testing of drug targets and drug candidates for the treatment of relevant CNS disorders. Strong habituation phenotype was already found in the fly model of a certain type of intellectual disability (ref. Kramer et al. PLOS Biology, 2011, 9(1): e1000569).
While developing its platform, Aktogen is offering platform services and initiating collaborations with pharmaceutical companies.
The offered services include:
A. Drug target screening through behaviour mutant
B. Disease models
C. Behaviour assays
Aktogen also aims to establish contacts with medium-sized and large pharmaceutical companies to initiate further collaborative projects.
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| Movement tracking and olfactory jump response habituation system. This behaviour system is established for high-throughput testing of general activity (motility), shock reactivity and non-associative learning in the olfactory sensory modality. |
