CSO: Dr. Niva Segev Amzaleg
Nevrox, is a drug discovery company developing a neuroprotective small molecule modulator of protein disulfide isomerase (PDI) for the treatment of Huntington disease (HD) and Amyotrophic Lateral Sclerosis (ALS).
PDI, is a thiol-oxireductase protein located in the endoplasmic reticulum (ER), serves two major functions: (1) general chaperone activity; (2) oxidation, reduction and isomerization of protein disulphide bonds. A by-product of the latter function is generation of reactive oxygen species (ROS), specifically H2O2. While ROSs have various physiological roles, their accumulation, known as oxidative stress, is toxic to cells. In healthy cells, accumulation of ROSs is prevented by the cell’s natural antioxidant mechanisms, but in neurodegenerative diseases, oxidative stress is considered a major factor in ongoing cell damage. In light of the physiological roles of ROSs, general ROS targeting has shown disappointing therapeutic effect. Inhibition of PDI’s redox activity may provide specific, disease relevant, ROS targeting.
Neurodegenerative disorders constitute a class of diseases that express characteristic misfolded proteins that aggregate and induce neuronal toxicity and death.
Huntington disease (HD) is one such fatal protein misfolding disease that afflicts primarily medium spiny neurons in the striatum. HD is caused by expansion to more than 36 CAG trinucleotide repeats in the huntingtin gene (Htt). Although the mechanisms through which mutant Htt (mHtt) is deleterious to neuronal function remain elusive, accumulating data from HD models as well as from human post-mortem brain analyses suggest that endoplasmic reticulum (ER) stress and oxidative damage are important contributors to mHtt toxicity in neurons. HD is a rare disease that affects 5 to 10 per 100,000 people in the European and USA. Currently, there is no cure for HD and available treatments can only assist patients with management of selected symptoms.
ALS is characterized by the degeneration of upper motor neurons of the motor cortex and lower motor neurons of the brainstem and spinal cord. This degeneration results in symptoms of fatigue, muscle weakness and atrophy, followed by eventual paralysis. ALS is an orphan disease (estimated 50,000-70,000). Effects usually age ≥40 years, with peak incidence at 65-74 years. Median survival is only 3-4 years from onset. 15% of patients live over 5 years, and only 5% over 10 years. Sporadic ALS accounts for 90-95% of cases, and hereditary ALS for the remaining 5-10%. There are only two approved drugs: Riluzole and Radicava with most patients receive Riluzole.
Niva Segev-Amzaleg, PhD, CSO
PhD and Postdoctoral Studies from Tel-Aviv University in neuroimmunology research focusing on stroke therapy, neuroprotection and glia. Worked at Teva as part of R&D team, including innovative CNS research and generic drug development. Last years gained experience in pharmacokinetic studies and project management.
Niv Dobzinski, PhD, Scientist
Niv has received his Ph.D. at the Weizmann Institute and was a post-doctoral fellow at UCSF, San Francisco. In his Ph.D. Niv was studying the molecular mechanism of neurodegenerative diseases and stress response in cells, while as a post-doc he was studying the ER Unfolded Protein Response at the lab of prof. Peter Walter at UCSF. Niv is a highly experienced cell biologist with a passion to elucidate mechanisms and molecular pathways.
Hadas Sar Shalom, PhD, Scientist
Hadas earned her Ph.D. at the department of Biomolecular Sciences, Weizmann Institute of Science, where she gained extensive experience in in-vivo and in-vitro models of cellular and molecular neurobiology. Hadas continued as a post-doctoral fellow at the department of Biological Regulation, investigating alpha Synuclein, Parkinson’s disease aggregated protein, in neuronal cell lines and differentiated human dopaminergic neurons.
Tamar Getter, PhD, Medicinal Chemist
Tamar has received training in organic and medicinal chemistry during doctoral and postdoctoral studies in Israel (Bar-ilan University, Department of Chemistry) and United states (University of California Irvine (UCI) Health Gavin Herbert Eye Institute). As a postdoc at UCI at the laboratory of Prof. Krzysztof Palczewski, she was responsible for the establishment and management of the Small-Molecule High Throughput Screening (HTS) facility. Tamar responsibility included development of cell-based assays, along with validation of the hit molecules and rigorous SAR studies to identify lead molecules, used as drug candidates for multiple vision related disorders.
Professor Brent R. Stockwell, PhD, Inventor and advisor
Dr. Stockwell is a Professor at Columbia University with joint appointments in the Department of Biological Sciences and the Department of Chemistry; he is also a member of the Motor Neuron Center and the Cancer Center at Columbia University Medical Center. Dr. Stockwell is the author of >100 scientific publications, 43 published patent applications and 18 issued US patent.