Abstract: The present invention relates to novel diagnostic, prognostic, predictive and pharmacodynamic properties with regard to amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD) with and without dementia components. The methods described herein will prove very useful in the development of diagnostic as well as treatment strategies for patients with amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD).

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); a method 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 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 subjects with motoneuron diseases, in response to therapeutic interventions, allows diagnostic monitoring for optimization of therapeutic regimen and strategy for individual subjects or for drug trials.

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules and microtubule-mediated axonal transport of cargo molecules in neurons), with or without dementia, and in dementia; methods for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease, with or without dementia, and in dementia; 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 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 microtubule-m

Abstract: 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

Abstract: Stable isotope labeling was used to measure dynamics of tubulin incorporation into microtubule subpopulations representing different neuronal compartments in the murine hippocampus. Neuronal microtubules were largely static. Basal turnover was highest in tau-associated (axona) and growth cone), lower in MAP2-associated (somatodendritic), and lowest in cold stable (axonal shaft) subpopulations. Intracerebroventricular glutamate injection stimulated label incorporation into axonal shaft and somatodendritic microtubules, the latter dependent on cAMP-PKA. Hippocampus-dependent memory formation after contextual fear conditioning was accompanied by increased assembly of MAP2- and cold stable-microtubules. Both microtubule assembly and memory formation were inhibited by the microtubule depolymerizing drug, nocodazole. This approach allows for correlation with behavioral measures of learning and memory and for the screening of candidate agents for stimulatory activities on learning memory.

Abstract: The Applicants have established a simple, rapid assay of measuring the dynamics of self-assembling systems of biological molecules, based on stable isotope labeling technology that can be used in intact animals including humans. Examples of self-assembling systems of biological molecules include microtubule polymers, actin filaments, amyloid-beta plaques or fibrils, prion plaques or fibrils, fibrin aggregates, tau filaments (e.g., neurofibrillary tangles), ?-synuclein filaments, and mutant hemoglo-bin aggregates. The method reveals constitutive differences in the dynamics of assembly and disassembly between tissues and is sensitive to the action of compounds that stabilize these dynamics.

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); a method 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 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 subjects with motoneuron diseases, in response to therapeutic interventions, allows diagnostic monitoring for optimization of therapeutic regimen and strategy for individual subjects or for drug trials.