Nerve growth factor (NGF) deficits are linked to Alzheimer's Disease (AD), due to the role of NGF on basal forebrain cholinergic neurons (BFCN). We have further established that a disequilibrium in NGF signaling and/or processing from its precursor proNGF is also directly and causally related to the aberrant activation of an amyloidogenic route to neurodegeneration. The therapeutic potential of using human NGF to provide a long-lasting cholinergic trophic support, thereby preventing or slowing cognitive decline in AD patients, has therefore a strong rationale. However, a simple and practical means of delivering NGF to the brain in a safe and long-term manner, limiting the undesired adverse effects of NGF in activating nociceptive responses, has represented a significant challenge. For this reason, pilot clinical studies have been performed so far with invasive approaches requiring neurosurgery. We obtained a proof of principle, in neurodegeneration animal models, of an alternative, non-invasive delivery of NGF through an intranasal route, which facilitates access of NGF to the central nervous system (CNS), while minimizing the biodistribution of NGF to compartments where it activates undesired effects, such as pain. The ideal NGF product for a non invasive NGF-based therapy would be a recombinant NGF that, while exhibiting an identical biological activity to that of human NGF, can be traced, against the endogenous NGF, in order to optimize the therapeutical dose range and meet the required therapeutic window. We describe an engineered mutein of hNGF, hNGF-61, that is selectively recognized, against endogenous NGF, by a specific antibody. hNGF-61 mutein has an identical potency and bioactivity profile as hNGF, in vitro and in vivo. Moreover, hNGF-61 and hNGF are equally effective in rescuing the behavioral and neurodegenerative phenotype in adult and aged AD11 anti-NGF mice. Finally, we demonstrated that intranasally delivered hNGF-61 is significantly more effective than ocularly applied hNGF-61, to determine phenotypic rescue in AD11 mice. The development of hNGF-61 towards clinical applications in AD patients is under way.

16 Feb 2009·Journal of Alzheimer's DiseaseQ3 · MEDICINE

Delivery of NGF to the Brain: Intranasal versus Ocular Administration in Anti-NGF Transgenic Mice

Q3 · MEDICINE

Article

Author: Stefanini, Barbara ; Covaceuszach, Sonia ; Spirito, Francesca ; Amato, Gianluca ; Ugolini, Gabriele ; Capsoni, Simona ; Vignone, Domenico ; Cattaneo, Antonino

Nerve growth factor (NGF) has a great potential for the treatment of Alzheimer's disease. However, the therapeutic administration of NGF represents a significant challenge, due to the difficulty to deliver relevant doses to the brain, in a safe and non-invasive way. We previously demonstrated the efficacy of a non-invasive delivery of NGF to the brain in animal models, by an intranasal route. Recently, topical eye application of NGF was proposed, as an option for the delivery of NGF to the brain. Here, we compare the efficacy of the two delivery routes of hNGF-61, a recombinant traceable form of human NGF, in the mouse neurodegeneration model AD11. The intranasal administration appeared to be significantly more effective than the ocular one, in rescuing the neurodegenerative phenotypic hallmarks in AD11 mice. The ocular administration of hNGF-61 showed a more limited efficacy, even at higher doses. Thus, NGF nasal drops represent a viable and effective option to successfully deliver therapeutic NGF to the brain in a non-invasive manner.

07 Oct 2008·Journal of Alzheimer's DiseaseQ3 · MEDICINE

Towards Non Invasive Nerve Growth Factor Therapies for Alzheimer's Disease

Q3 · MEDICINE

Review

Author: Cattaneo, Antonino ; Paoletti, Francesca ; Capsoni, Simona

In the past thirty years, nerve growth factor (NGF) has received much attention for its potential role as a therapeutic agent for Alzheimer's disease (AD) due to its neurotrophic activities on basal forebrain cholinergic neurons. This attention has been renewed by recent findings that provide new causal links between defects in NGF signaling, transport or processing to the activation of the amyloidogenic route and, more generally, to AD neurodegeneration. Thus, the concept of therapeutic administration of human recombinant NGF in AD patients has a strong rationale, being further validated by recent and ongoing clinical trials with a gene-therapy approach. However, the widespread clinical application of gene or cell-therapy strategies for the delivery of NGF to AD patients seems unpractical, and it would be more advantageous to have non-invasive methods, that should also limit the adverse effects of NGF in activating nociceptive responses. This review will describe: 1) the data from preclinical and clinical studies underlying the rationale of NGF as a potential therapeutic agent for AD; and 2) the alternative strategies to reach adequate concentrations of NGF in relevant brain areas while preventing the onset of adverse effects.

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29 Mar 2005

·www.biospace.com

Venture Valuation Strengthens Advisory Board

Gamil G. de Chadarevian, Vice Chairman of the Board of Antigenics Inc. (NASDAQ: AGEN) has recently joined the advisory Board of Venture Valuation, Switzerland. He will advise and support the company on its expansion of the Biotech and Life Sciences Company Database "Biotechgate" in Europe and Venture Valuations assessment and valuation services. Zurich, April 2005 - With the addition of Gamil G. de Chadarevian, Venture Valuation strengthens its Biotechnology and Life Sciences focus even more. Mr. de Chadarevian will provide his network and knowledge to extend Venture Valuations Biotechgate Company Database ( ), an extended company directory of European companies in the biotechnology and life sciences field. Current featured countries include Austria ( ), France ( ), Italy ( ) and Switzerland ( ). Mr de Chadarevian was very instrumental starting the Italian Biotech Database which was developed in cooperation with the governmental organization InvestinItaly. As a serial entrepreneur, investor, world citizen and biotechnology expert, Gamil G. de Chadarevian supports Venture Valuation also in the expansion of its independent, third party valuations. He is on the Advisory Board of Venture Valuation along with Dr. Christian Suter, formerly Director of Research and Development of Hoffmann-LaRoche's Vitamin Division and Prof. Cuno Pümpin, Extraordinarius for management at the University of St. Gallen, entrepreneur and also on the Advisory Board of Invision and The Blackstone Group. About Gamil G. de Chadarevian Gamil G. de Chadarevian has served as Vice Chairman of the Board since 1995 and as Executive Vice President International from 1998 to 2001 of Antigenics Inc. (NASDAQ: AEGN). Until April 1998, Mr. de Chadarevian was Managing Director of Special Projects at Alza International and the Vice President of Corporate Development for Corange London Limited, two pharmaceutical companies. Prior to 1992, he held positions at Pasfin Servizi Finanziara SpA, GEA Consulenza and Credit Suisse. Mr. de Chadarevian is the founder and Lead Director of OphthalmoPharma Ltd. and a co-founder of Ikonisys Inc. and CambriaTech Holding SA. He serves on the advisory board of Syntek Capital AG and is a non-executive board member of Friends of San Patrignano, Inc., a charitable organization. In Italy he is an advisor for biotechnology to Sviluppo Italia, a government agency dedicated to promoting inward investment opportunities, and to Lay Line Genomics SpA, a biotechnology company. Mr. de Chadarevian received his degree from the University of Zurich in Switzerland. About Venture Valuation Venture Valuation specializes in independent, third party assessment, valuation and monitoring of emerging high growth companies in industries such as biotechnology, med-tech and high-tech. Services are provided in the form of proprietary software ( ) and independent Valuation Reports to entrepreneurs (seed to pre-IPO) and investors. With offices in Switzerland, Germany, Canada and South Korea, Venture Valuation has an experienced team of scientists and business professionals with expertise in finance, biotechnology, pharmaceutical and high technology industries. Further more, Venture Valuation has initiated, maintains and further develops the Biotech and Life Sciences Databases Biotechgate ( ) For further information, please contact: Venture Valuation AG Patrik Frei, CEO patrik.frei@venturevaluation.ch Badenerstrasse 18 8004 Zurich Switzerland Tel. +41 (43) 321 86 60 Fax +41 (43) 321 86 61 Austrian Biotech Database French Biotech Database Italian Biotech Database Swiss Biotech Database European / Global Biotech Database

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Humanized anti-NGF mab(Lay Line Genomics SpA) ( NGF )	Osteoarthritis, Knee More	Discontinued
huIM-13	Alzheimer Disease More	Pending
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