Compositions and methods of treatment using modulators of...

G - Physics – 01 – N

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G01N 33/68 (2006.01) A61K 31/4741 (2006.01)

Patent

CA 2725138

The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); methods for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can improve MT-mediated transport of " synaptic vesicle cargo" molecules along and through axons; the discovery that such modulation of altered microtubule dynamics and improvement in MT-transport of molecules along axons can provide marked neuroprotective therapy for living subjects with motoneuron diseases, including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in response to therapeutic interventions in subjects with motoneuron diseases, allows diagnostic monitoring, to optimize therapeutic regimens and treatment strategies in individual subjects or in drug trials. The monitoring involves measuring isotope enrichment in secreted synaptic vesicle cargo molecules.

Linvention concerne une nouvelle cible thérapeutique pour des maladies des neurones moteurs (dynamique touchée des microtubules dans les neurones) ; de procédés de mesure de létat de lactivité de cette cible thérapeutique chez des sujets ayant une maladie des neurones moteurs établie, naissante ou potentielle ; la découverte dagents médicamenteux qui modulent la dynamique des microtubules neuronaux chez les sujets vivants atteints de maladies des neurones moteurs ; la découverte que ladministration de tels agents, seuls ou en combinaison, peut améliorer le transport à médiation par MT de molécules « cargo » le long et à travers des axones ; la découverte quune telle modulation de la dynamique touchée des microtubules et que lamélioration du transport MT de molécules le long daxones peuvent fournir une thérapie neuroprotectrice marquée pour des sujets vivants atteints de maladies des neurones moteurs, comprenant un retard des symptômes et une prolongation de la survie, et la découverte que la surveillance de la dynamique des microtubules neuronaux en réponse à des interventions thérapeutiques chez des sujets atteints de maladies des neurones moteurs, permet une surveillance de diagnostic, pour optimiser des régimes thérapeutiques et des stratégies de traitement chez des sujets individuels ou dans des essais de médicament.

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