I am excited about another iteration of capablilities with our new:
Intra-i-Fect Tissue Specific siRNA Kits.

These kits are designed to deliver siRNA in vivo via intravenous injections with high efficiency to specific tissue in rats and mice. The protocol involves these simple steps: prep, mix, dry, hydrate and inject.

They are developed using a proprietary platform that uses nano-particles as the delivery vehicle. This platform enables:

• Effective delivery (60%+ knockdown) with no toxicity.
• Scalable to high throughput siRNA based gene screening.
• Consistent and reproducible results

Getting Started with Alphagenix                     Steve is an advisor, collaborator and friend. He has the innate ability to bring his his scientific expertise and entrepreneural insticts together in a way that anticipates emerging needs of the research community we both serve. He is an expert in immunology, neuroscience, virology and regenerative medicine (stem cells).  Most notably, he is the sole inventor on the patent that formed the basis for using the Nodaviruses as vaccine and gene therapy vectors U.S. Patent 6,171,591. These vaccines are in various stages of preclinical development as are protoype therapeutic vaccines for neurodegenerative diseases.  Our two companies first worked together to identify and manufacture several important stem cell markers. We tested potency on our STEMEZ hNP1TM Human Neural Progenitors. They proved to effective. This confirmed Steve’s ability to identify, design and make these markers. The demand for them continues to grow. These successes were a prelude of good things to come. Current Focus Steve is currently  developing novel products and technologies for basic and clinical research with a particular emphasis on stem cell markers, biomaterials and regenerative medicine. The biomaterials product focus involves the design and application of 3-dimensional biomaterials comprised of extracellular matrix components and peptide nanofibers that have cell culture and tissue engineering applications. In addition, the company conducts regenerative medicine research that involves basic science and translational preclinical research using stem cell regulatory network discoveries and novel preclinical studies utilizing animal models with a focus on neurological disease and diabetes. He is a contributor to: Stem Cell Therapy for Neurological Diseases Stem cell therapy for the treatment of acute and chronic neurological diseases

2001-Present-President-Alphagenix 2006-2007-CSO-Neuromics 2000-2001-President-AmProx, Inc 1996-2004-President and CSO-Pentamer Pharmaceuticals 1996-1997-Sr. Research Fellow-Medical Biology Institute. 1995-1997-Research Associate-Scripps Research Institute 1995 PhD Purdue University Musashi-1 Antibody Image: Musashi (green) staining of neural rosettes(human). Nuclei are counterstained blue (DAPI). Image courtesy of Dr. Steve Stice and Dr. Patricia Wilson, University of Georgia.

Harting, Matthew T., Cox, Charles S. and Hall, Stephen G.  Adult Stem Cell Therapy for Neurological Disease: Preclinical evidence for cellular therapy as a treatment for neurological disease. In Vemore and Vinoglo (eds): Regulatory Networks in Stem Cells. Humana Press, pp 561-573, (2009). More information.

Specific Projects

1. Steve has 3 major projects underway:
   In collaboration with Dr.  Charles Cox , Distinguished Professor, UT Medical School @ Houston, Steve has been using stem cells to treat  Traumtaic Brain Injury (TBI) in Rat. Neural stem cells transplanted into the site of injury. In this model, treated rats showed injury significantly improved motor skills with a moderate recovery in cognitive ability. This research forms the base for eventually repairing damage in humans suffering TBI. Methods and reagents developed also could be useful for basic research and drug discovery.
2. Steve is working with Burnham Institute to develop methods for using  Human Mesenchymal Stem Cells to regenerate beta cells. This research holds promise for type 1 diabetics.
3. Steve developing biomaterials including extracellular matrix proteins in novel cell culture systems and synthetic peptide nanofibers for these purposes.  It is investigating stem cells and genetically engineered cells and their interaction with these biomaterials, which has the ability to increase the efficacy of cell therapy. This is highlighted by a human laminin sytem that shows promise in restoring function in Muscular Dystophry.

The last project is promising enough that it could lead to funding for phase 1 testing.

I will continue to keep you posted on progress. I am excited about the new regeants and method that evolve from Steve’s Research. As these prove to work in unique and novel ways, the will become available to Neuromics.

STEMEZ hN2 Primary Human Neurons

I have profiled Steve Stice’s research here. The focus has been the excellent research results he and his team at ArunA Biomedical have generated with STEMEZ(TM) hN2 Human Neurons and hNP1 Human Neural Progenitors.

The story continues. He will be presenting the latest at the 9th Annual World Pharmaceutical Congress in Philadelphia, June 14. Topics include: using these neural cell lines to study neurotoxicity in cell-based assays and disease modeling.  Recent work conducted in outside laboratories demonstrates that these lines are more sensitive to environmental toxicants than traditional cellular models.

Sample high throughput assay applications:

• Cell morphology and neurite outgrowth
• Cell signaling and transcription factor expression
• Receptor and ion channel function
• Cytotoxicity
• Apoptosis, genotoxicity and DNA damage

These capabilities has been confirmed by our customers. I look for the use of the STEMEZ cell lines to continue to grow as researchers discover their value in Drug Discovery and Basic Neuroscience capabilities.

Dr. Steve Hall

Dr Steve Hall has been a friend, collaborator and mentor since I purchased Neuromics. This includes being a Neuromics’ Premier supplier of Stem Cells and Related Markers, Media and Methods. Steve is currently President at AlphaGenix, Inc.

His expertise includes developing novel products and technologies for basic and clinical research with a particular emphasis on stem cell markers, biomaterials and regenerative medicine. The biomaterials product focus involves the design and application of 3-dimensional biomaterials comprised of extracellular matrix components and peptide nanofibers that have cell culture and tissue engineering applications. In addition, the company conducts regenerative medicine research that involves basic science and translational preclinical research using stem cell regulatory network discoveries and novel preclinical studies utilizing animal models with a focus on neurological disease.

He is a contributor to: Stem Cell Therapy for Neurological Diseases Stem cell therapy for the treatment of acute and chronic neurological diseases

Harting, Matthew T., Cox, Charles S. and Hall, Stephen G.  Adult Stem Cell Therapy for Neurological Disease: Preclinical evidence for cellular therapy as a treatment for neurological disease. In Vemore and Vinoglo (eds): Regulatory Networks in Stem Cells. Humana Press, pp 561-573, (2009). More information.

Stay tuned for Steve’s backstory in June!

A431 cells, treated with predetermined IC50
concentration of novel anticancer agents, fluoresce green and orange-red with MitoPT JC-1. Data courtesy of Zayas/ Carro, Universidad Metropolitana.

Anticancer Effects of Flavonoid Derivatives Isolated from Millettia
reticulata Benth in SK-Hep-1 Human Hepatocellular Carcinoma Cells.
SC Fang, CL Hsu, HT Lin, GC Yen. J. Agric. Food Chem., Jan 2010, 58
(2), pp 814–820.

Mechanisms of Apoptotic Effects Induced by Resveratrol,
Dibenzoylmethane, and Their Analogues on Human Lung Carcinoma Cells.
CJ Weng, YT Yang, CT Ho, GC Yen. J. Agric. Food Chem., Jun 2009; 57
(12), pp 5235–5243.

Of Chemicals and Parkinson’s Disease

Two recent studies have linked the chemical TCE, an industrial solvent, to the increased risk of Parkinson’s disease.  The first study, led by the University of Kentucky’s Don M. Gash and John T. Slevin, established a clear link between trichloroethylene and parkinsonism , which is a group of nervous disorders closely associated with Parkinson’s.

 The study investigated a group of people who had been occupationally exposed to TCE for over twenty-five years. Gash and Slevin found that of the 134 participants interviewed, 14–the group that worked closest to the TCE vat cleaning industrial parts–showed strong signs of Parkinsonism. 13 other patients who had worked further from the TCE source also showed signs of the disorder, although in milder form. The University of Kentucky study extended its investigation by exposing rats to TCE. The rats’ mitochondrial function was substantially inhibited and their dopamine-producing cells were severely damaged.

 A more recent study , revealed in January, established an even stronger link between TCE and Parkinson’s. Dr. Samuel Goldman, a researcher at the Parkinson’s Institute in Sunnyvale, California, examined 99 sets of twins in which one twin had Parkinson’s and the other didn’t. Goldman and his team gathered job histories from the group of twins and had an industrial hygienist evaluate the twins’ level of chemical exposure. The study found that those exposed to TCE had an almost six-fold increased risk of developing Parkinson’s. Occupations that often involve exposure to TCE include machinists, laundry cleaners, and electricians.

Even though the most recent findings are substantial, the idea that chemicals may be associated with increased risk of developing Parkinson’s is not very new. Earlier studies have suggested that certain pesticides and herbicides may increase risk as well.

Not all chemicals are bad news for Parkinson’s patients. A brain chemical, identified only about twenty years ago and named after the video game character, Sonic Hedgehog , has been shown to decrease the risk of developing Parkinson’s, meaning that increasing the chemical may be a viable treatment for the disease. Another study has suggested that urate, a naturally occurring chemical in the blood, may slow the progression of Parkinson’s, although the chemical has been proven to cause gout.

By-line:

This guest post is contributed by Pamelia Brown, who writes on the topics of associate degree .  She welcomes your comments at her email Id: pamelia.brown@gmail.com

I am excited to present a recent publication that includes use of this kit to study Opioid-Induced Hyperalgesia. In this study Dr. Zaijie Jim Wang and his team at University of Illiniois Chicago down regulate CaMKII alpa expression. Their data implicates, for the first time, an essential role of CaMKII alpha as a cellular mechanism leading to and maintaining opioid-induced hyperalgesia.

Yan Chen, Cheng Yang, and Zaijie Jim Wang. Ca2+/Calmodulin-Dependent Protein Kinase II Is Required for the Initiation and Maintenance of Opioid-Induced Hyperalgesia. The Journal of Neuroscience, January 6, 2010, 30(1):38-46; doi:10.1523/JNEUROSCI.4346-09.2010.

…KN93 and KN92 were administered intrathecally by percutaneous puncture through the L5-L6 intervertebral space, as described previously (Hylden and Wilcox, 1980; Chen et al., 2009). A lateral tail flick was considered as success of the intrathecal injection. To inhibit CaMKII, CaMKII was targeted by small interfering RNA (siRNA). Four days after morphine pellet implantation, mice were treated with CaMKII siRNA (5′-CACCACCAUUGAGGACGAAdTdT-3′, 3′-dTdTGUGGUGGUAACUCCUGCUU-5′) (Zayzafoon et al., 2005) or Stealth RNAi negative control (Invitrogen) (2 µg, i.t., twice per day for 3 consecutive days). These oligos were mixed with the transfection reagent i-Fect (Neuromics), in a ratio of 1:5 (w/v) (Luo et al., 2005). Mechanical and thermal sensitivity tests were performed daily…

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Teacher, Mentor and Friend    Dr. Pat Carr has been a key figure in helping shape the direction of my company. He has a gift for communicating the nuances of his research and coaching me on how to best serve labs like his. Based on these interactions, it came as no surprise to learn of his being Recognized for Excellence in Teaching, Research and Service at University of North Dakota. “Dr. Carr has a magic way of teaching,” said second-year medical student, Tyson Bolinske. “He is able to take the most difficult topics and, through detailed notes, logically break down the material.” From a recent dialog, I learned of his growing work on the Ventral Horn and search for root causes of Amyotrophic Lateral Sclerosis (ALS).   I wanted to learn more! I would like to thank Pat for agreeing to share his story and giving me the opportunity to feature highlights in  “News Behind the Neuroscience News”.  Information on ALS ALS is an insidious disease.  It is a progressive neurodenerative disease that is always fatal. Approximately 5600 new cases are diagnosed each year. Average survival is typically 3-5 years from onset. The most common form of ALS in the United States is “sporadic” ALS. It can happen to anyone at anytime.  The other is the inherited form named “Familial” ALS (FALS). Only about 5 to 10% of all ALS patients appear to have FALS. As the disease progresses the symptons become more acute. Paralysis spreads through the body affecting  speech, swallowing, chewing and breathing. Ventilator support is need in late stages  Pat’s Journey Pat took the “road less traveled”.  He was a passionate hockey player in Canada. He  concluded in his late teens that he was not at a level to take this road to wealth and fame.

Pat Carr 06/04–present Associate Professor, Department of Anatomy & Cell Biology, School of Medicine and Health Sciences, University of North Dakota  1996–98 Research Associate/Adjunct Assistant Professor/Auxilliary Assistant Professor, Department of Anatomy;Wright State University  07/98–06/04 Assistant Professor, Department of Anatomy & Cell Biology, School of Medicine and Health Sciences, University of North Dakota Postdoc, National Institutes of Health, Neuroscience, 1994-96 Postdoc, University of Manitoba, Neuroscience, 1992-1994     Ph.D., University of Manitoba, Physiology, 1992

Next was a stint as an automechanic in Brandon, Canada. The discipline and logic involved in fixing cars catalyzed an interest in Science which led to him going to Brandon University to study Geology. When the oil market collapsed in 1983, he decided to change his studies to Zoology and earned a BS in 1984.

A passion was sparked when he did field research in the Canadien Rockies studying parasites in Columbian Ground  Squirrels. He loved it, but recognized the limited value of continuing thsese studies. This lead to the wide open field of Neuroscience and the opportunity to study and solve problems that could benefit mankind. His graduate work at University of Manitoba and focusing on Neuropathic Pain and the Dorsal Horn. He then moved on to studying Ventral Horn and Motor Control Function for his Post Doc at Wright State.

From Pain to ALS

It was Pat’s work in Pain at the University of North Dakota that brought me into initial contact with him. He generously put some of our key Pain/Inflammation and  Neurotransmission Research Antibodies through their paces. These included some of our Neuropeptide and Neuropeptide Receptors , P2X Receptors and TRPV1s (Vanilloids).

His previous work in studying the Ventral Horn combined with a colleagues mouse model of ALS combined to create a prefect opportunity to advance the understanding of ALS.  Pat cautioned me with this insight:  ”sometimes it is  not what you want to study; it is what you can study.  The model is  SOD1 (superoxide dismutase 1) which is core to FALS.(occurs in only about 10% of the ALS cases).

Pat is broadening the play field by looking at what else is happening in sporadic ALS vs FALS. Specifically, he is looking at modulation of alpha Motor Neurons and how the activity of adjacent Renshaw Cells impact signaling and modulation.  Renshaw Cells act as a “governor” on the activity of these alpha Motor Neurons. 

He is drilling down by studying the signaling of ChAT (Choline Acetyltransferase), VAChT (Vesicular acetylcholine transporter) and related molecules. By gaining a deeper understanding of how Renshaw Cells signaling changes the activity of alpha Motor Neurons in ALS,  Pat and his team are taking steps towards discovering roots causes.

As these root causes are further illuminated, I will be reporting specifics in my blog.

Dr. Mark Tuszynski and his team of researchers at USCD recently published work that tested their hypothesis that chemotropic mechanisms would guide regenerating spinal cord axons to appropriate brainstem targets.

Laura Taylor Alto, Leif A Havton, James M Conner, Edmund R Hollis II, Armin Blesch & Mark H Tuszynski. Chemotropic guidance facilitates axonal regeneration and synapse formation after spinal cord injury. Nature Neuroscience. Published online: 2 August 2009 | doi:10.1038/nn.2365.

Their study included use of Neuromics’ NT-3 Antibody.