The General Hospital Corporation

Other

Avicena Group, Inc.

M Flint Beal

Rima Kaddurah-Daouk

Ghaleb Daouk

Matthew J During

Andrew Freese

Kenton J Swartz

The present invention relates to the use of creatine compounds including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer's disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

Use of creatine or creatine analogs for the treatment of diseases of the nervous system

The present invention relates to the use of creatine compounds including creatine, creatine phosphate or analogs of creatine, such as cyclocreatine, for treating diseases of the nervous system. Creatine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases. The Creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine; (3) creatine analogs which can act as reversible or irreversible inhibitors of creatine kinase; and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

Neurological diseases such as Huntington's caused by the toxic effects of excetatory amino acids are alleviated by administering metabolic precursors of kynurenic acid to afflicted individuals. These metabolic precursors include kynurenine and tryptophan. Since the amount of kynurenic acid in Huntington's Disease patient's brains is less than that in normal individuals and such decrease is associated with the lesions found in the formation of the lesions. This occurs because kynurenic acid is an inhibitor of excitatory amino acid interactions at their receptors.

Treatment of neurological diseases by increasing brain concentrations of kynurenic acid

Methods for inhibiting a nitric oxide-mediated pathological condition and a neurodegenerative disease such as Parkinson's disease, Huntington's disease, Alzheimers's disease, and amyotrophic lateral sclerosis in a human patient, comprising administering an effective amount of a nitroindazole capable of inhibiting a neuronal nitric oxide synthase.

Growing community of inventors

New York, NY, United States of America

M Flint Beal