Project: DIAGNOSIS OF SARCOPENIA

DISARCO project is aimed at the clinical development of a biochemical test for the diagnosis of sarcopenia. Sarcopenia is an age-related muscle atrophy that contributes to a significant part of mobility disability in the elderly. A comprehensive, simple, generally applicable and low cost diagnostic method for sarcopenia is not yet available. DISARCO will also address one of the most important problems associated with sarcopenia, namely frequent falls. Falls pose a major threat to many sarcopenia patients. Although the clinical problem of frequent falls has long been recognized it has not received the necessary attention. Generally it is accepted that the falls are caused by the inability of sarcopenia patients to adequately respond to slight imbalances that occur during movement (walking). In this program the factors underlying falls are investigated by accelerometric studies relating concentrations in serum of a small protein, CAF with the loss of muscle capacity and the associated loss of central and peripheral neurological function involved in gait, balance and coordination. Neurotune AG has developed a preliminary laboratory test in the form of an immunoassay focused on the measurement of CAF linked to the functioning of neuromuscular junctions. CAF is a small proteolytic fragment of agrin (an extra-cellular proteoglycane secreted by the neuron axons) soluble and detectable in serum. The rationale behind the blood CAF monitoring is that agrin plays an important role in the formation and stabilization of neuromuscular junctions (NMJs), which are specialized for the communication between motoneurons and muscle fibres. Depletion of agrin leads to a destabilization of the NMJs. In addition, Neurotune has generated transgenic mice over-expressing neurotrypsin. These mice have increased CAF levels, are weak and develop sarcopenia at young age. Neurotune AG's working concept is that an increased production of CAF (corresponding to an increased activity of neurotrypsin) implies the presence of sarcopenia. The concept has been proved in a small clinical study on patients from nursery homes suffering from sarcopenia-like symptoms._x000D_However, these preliminary results need confirmation with larger control and patient groups with state of the art inclusion and exclusion criteria using a certified ELISA test. _x000D_The proposed project, starting from Neurotune AG's preliminary assay and the project P's ongoing clinical studies, will develop:_x000D__x000D_• An ELISA assay for CAF suitable for clinical use;_x000D_• A clinical validation and preliminary calibration._x000D__x000D_The clinical CAF ELISA assay will be developed by the Microcoat Biotechnologie GmbH P in collaboration with Neurotune AG. Microcoat is an expert company specialized in clinical IVD test development. The clinical validation and preliminary calibration of the ELISA will be done by Klinikum Nürnberg in collaboration with the Hochschule für Technik Rapperswil. _x000D__x000D_Clinical diagnosis of sarcopenia is not simple for the following reasons:_x000D_• There is no absolute level of lean mass, body cell mass, or muscle mass for comparison. _x000D_• There is no accepted threshold of functional decline at which sarcopenia is implied._x000D__x000D_We are confident that our ELISA CAF test will fill the gap and become the missing definite tool for reliable diagnosis of sarcopenia. _x000D_The planned clinical validation of the ELISA (and preliminary calibration) will be performed through the execution of an experimental design suitable to compare the biochemical test data with other types of data and information (muscle mass, muscle strength, MUNE and accelerometric tests) currently used to diagnose sarcopenia._x000D__x000D_

Acronym	DISARCO (Reference Number: 5599)
Duration	01/07/2010 - 30/06/2012
Project Topic	The scope of the project is the development of an ELISA immunoassay for the diagnosis of sarcopenia a debilitating muscles disorder affecting frequently elders._x000D_ Neurotune AG will provide the scientific background, Microcoat GmbH the ELISA technology and the academic Ps the clinical trial.
Project Results (after finalisation)	1. The current CAF-ELISA, developed within the project, measures CAF(0). CAF(0) comes from Agrin without any insert. CAF(0) seems to be more a marker for kidney function than for sarcopenia. Further research reveals that CAF(8) with inserts should be able to detect sarcopenic patients caused by loss of neuromuscular junctions (NMJs). _x000D__x000D_2. The Motor unit number index (MUNIX) of the hypothenar muscle measured in the recruited study participants seems to be a marker for motoneuron loss responsible for the onset of sarcopenia._x000D_
Network	Eurostars
Call	Eurostars Cut-Off 4

Project partner

Number	Name	Role	Country
4	Friedrich-Alexander University Erlangen-Nürnberg - Department of Geriatric Medicine	Partner	Germany
4	Hochschule für Technik Rapperswil - Institute for Communication Systems	Partner	Switzerland
4	MicroCoat Biotechnologie GmbH	Partner	Germany
4	NEUROTUNE AG	Coordinator	Switzerland