Johns Hopkins University

Valted, LLC

Other

The United States of America

Sungkyunkwan University

Valina L Dawson

Ted M Dawson

Han Seok Ko

Solomon H Snyder

Jooho Shin

Seulki Lee

Magdalena Scully

Seung Pil Yun

Joseph P Steiner

Edythe D London

George R Uhl

David S Bredt

Jie Zhang

Richard J Traystman

Allen S Mandir

Shaida A Andrabi

Jun Bao

Mikael J Eliasson

Ho Chul Kang

Andrew Pieper

Tae-In Kam

Liana Rosenthal

Shaida Andrabi

Areum Jo

Patricia D Hurn

Kenji Sampei

Joo-ho Shin

Yunjong Lee

Poly(ADP-ribose) (PAR) is a protein implicated in numerous neurodegenerative disease states including Parkinson's disease (PD). To date, no routine laboratory test has been developed to diagnosis, assess or monitor patients suffering from PD. Disclosed herein a novel method to assess the PAR concentration in the cerebral spinal fluid (CSF) of a patient and correlate that concentration to the medical condition of a patient with PD. Also disclosed is the use of PAR as a biomarker for PD.

Detection of PAR in the CSF of patients with Parkinson's disease

The present invention relates to compositions and methods for treating neurodegenerative conditions using GLP-1r agonists. In certain embodiments, long-acting GLP-1r agonists have neuroprotective and disease modifying effects on the central nervous system.

Long-acting GLP-1r agonist as a therapy of neurological and neurodegenerative conditions

Long-acting GLP-1R agonist as a therapy of neurological and neurodegenerative conditions

Research into neuroprotective mechanisms has at its heart the goal of developing new therapeutic strategies to treat patients. For example, the compositions and induction strategies disclosed herein have use for acute injuries such as stroke or trauma, and would be extremely useful in treating patients undergoing cardiac bypass surgery, neurosurgery or other surgical cohorts where ischemia is a risk. Further, patients with subarachnoid hemorrhage, transient ischemic attacks, soldiers at risk for blast injury or patients suffering from chronic neurodegenerative diseases would also benefit from enhanced neuronal survival based upon the techniques and compositions disclosed herein. In addition, protecting against cell death by, for example, interfering with PAR polymer signaling via the compositions and processes disclosed herein, offers new therapeutic strategies for the treatment of neurologic disorders.

Treatment and prevention of pathological conditions using iduna related techniques and compositions

Parkinson's disease is caused by the preferential loss of substantia nigra dopamine neurons. A Parkin Interacting Substrate, PARIS (ZNF746) is identified. The levels of PARIS are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human brain Parkinson's disease patients. PARIS represses the expression of the transcriptional co-activator, PGC-1&#x3b1; and the PGC-1&#x3b1; target gene, NRF-1 by binding to insulin response sequences in the PGC-1&#x3b1; promoter. Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons that is PARIS dependent. Overexpression of PARIS causes selective loss of DA neurons in the substantia nigra, which is reversed by either parkin or PGC-1&#x3b1; co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Transcriptional repression leading to parkinson's disease

Transcriptional repression leading to Parkinson's disease

Immunophilin-binding agents inhibit the phosphatase calcineurin, leading to the increased phosphorylation of certain brain proteins, including nitric oxide synthase. The increased levels of phosphorylation of nitric oxide synthase inhibits the enzymatic production of nitric oxide. Thus the neurotoxic effects of glutamate, which are ordinarily the result of vascular strokes and other neurodegenerative diseases, are minimized, because the neurotoxic effects are at least partially mediated by nitric oxide. Thus immunophilin-binding drugs can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.

Immunophilin-binding agents prevent glutamate neurotoxicity associated with vascular stroke and neurodegenerative diseases

Neutral tissue damage resulting for ischemia and reperfusion injury or neurodegenerative diseases can be prevented by administering therapeutically effective amounts of certain selective inhibitors of poly(ADP-ribose)polymerase. The inhibitors can be administered intravenously, intraperitoneally, intramuscularly, intraventricularly, or orally. They can be administered as a capsule or tablet containing single or divided dose. Alternatively, the inhibitors can be administered as a sterile solution, suspension or emulsion.

Method of using selective parp inhibitors to prevent or treat neurotoxicity

Inhibitors of poly(ADP-ribose) synthetase can be used to prevent neurotoxicity mediated through N-methyl-D-aspartate (NMDA) receptors. Poly(ADP-ribose) synthetase inhibitors can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease.

Inhibitors of poly(ADP-ribose) synthetase and use thereof to treat NMDA

Inhibitors of nitric acid synthase can be used to prevent neurotoxicity mediated through glutamate receptors. Nitric oxide synthase inhibitors can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.

Inhibitors of nitric oxide synthase and use thereof to prevent glutamate

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Baltimore, MD, United States of America

Valina L Dawson