Publication Highlights Mode of Action for Santhera's Catena and its Relevance for Mitochondrial Disorders

Top Quote Santhera Pharmaceuticals (SIX: SANN) announced today the publication of details on the mode of action of idebenone (brand name Catena) in PLoS ONE (Public Library of Sciences ONE) End Quote
  • (1888PressRelease) April 06, 2011 - For the first time, a detailed biochemical pathway is described how idebenone can restore energy production in cells which are deficient in complex I of the mitochondrial electron transport chain. The observed activities confirm a unique mode of action and separate the effectiveness of idebenone from Coenzyme Q10. The data confirm the rationale for the use of idebenone in the treatment of mitochondrial disorders with impaired complex I function such as Leber's Hereditary Optic Neuropathy (LHON).

    "From previous studies it was clear that idebenone can transfer electrons onto complex III of the mitochondrial electron transport chain. This new work now closes the gap in our understanding how exactly this transfer is accomplished", summarized Thomas Meier, Santhera's Chief Scientific Officer. "Biochemical and cellular experiments now show that the cytosolic enzyme NQO1 uses idebenone as a substrate, which in turn can transport electrons into the mitochondria and onto complex III. This shuttling of electrons effectively by-passes the deficient complex I and increases the levels of ATP."

    Idebenone, a short-chain benzoquinone, holds therapeutic potential for several mitochondrial and neuromuscular disorders. Researchers at Santhera now found that idebenone upon reduction by the cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) generates a cytosolic-mitochon­drial electron shuttle that can effectively bypass complex I of the mitochondrial electron transport chain and increase cellular energy levels. Interestingly, this mechanism is not shared with long-chain quinones, such as Coenzyme Q10, which is a poor substrate for NQO1. This mode of action for idebenone is particularly relevant for disorders characterized by deficiencies of the mitochondrial complex I, such as Leber's Hereditary Optic Neuropathy (LHON), Mitochondrial Encephalomyopathy, and Lactic Acidosis and Stroke-like episodes (MELAS).

    [1] Haefeli RH, Erb M, Gemperli AC, Robay D, Courdier Fruh I, et al. (2011) NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels. PLoS ONE 6(3): e17963. doi:10.1371/journal.pone.0017963.

    About Santhera
    Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative pharmaceutical products for the treatment of severe neuromuscular and neurodegenerative diseases, an area of high unmet medical need which includes many orphan and niche indications with no current therapy. Santhera's first product, Catena, to treat Friedreich's Ataxia is marketed in Canada.

    For further information, contact
    Thomas Meier
    Phone: +41 (0)61 906 89 64
    thomas.meier ( @ ) santhera dot com

    Thomas Staffelbach, Head Public & Investor Relations
    Phone: +41 (0)61 906 89 47
    thomas.staffelbach ( @ ) santhera dot com

    Disclaimer/Forward-looking statements
    This communication does not constitute an offer or invitation to subscribe for or purchase any secu­rities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, un­certainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.

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