Up next will be Dr. Gerry Shaw.  Gerry is the founder and head of EnCor Biotechnology, Inc. His company is recognized for creating markers that are engines of Neuroscience and Stem Cell Research.

Dr. Gerry Shaw with Triumph MC

I am pleased to represent his company’s reagents. They are well designed, thoroughly tested and proven to work in my customers’ many application.

They have proven especially effective in working in cell based assays using our eSC derived hNP1 human neurons and e18 primary rat hippocampal neurons.

Applications include the study of TBI, SCI, ALS, AD, MS and PD.

Image:  hN2 cells stained with our chicken polyclonal antibody to Vimentin, in red. Islands of Hn2 cells form after 4 days in culture forming beautiful flower like structures. Vimentin is a well established marker of early differentiating neuronal lineage cells. Taken with a 10X objective lens. Blue staining is the nuclear DNA.

hN2 Cells stained with Vimentin

I am seeing increasing demand for these cells as these capabilities are published. Here’s the latest:

A. Young, D.W. Machacek, S.K. Dhara, P.R. MacLeish, M. Benveniste, M.C. Dodla, C.D. Sturkie and S.L. Stice. Ion channels and ionotrophic receptors in a human embryonic stem cell derived neural progenitors. doi:10.1016/j.neuroscience.2011.04.039. Markers used:…mouse nonoclonal anti nestin (neuromics), mouse monoclonal anti tuj-1 (neuromics)…

Abstract: Human neural progenitor cells differentiated from human embryonic stem cells offer a potential cell source for studying neurodegenerative diseases and for drug screening assays. Previously, we demonstrated that human neural progenitors could be maintained in a proliferative state with the addition of leukemia inhibitory factor and basic fibroblast growth factor. Here we demonstrate that 96 h after removal of basic fibroblast growth factor the neural progenitor cell culture was significantly altered and cell replication halted. Fourteen days after the removal of basic fibroblast growth factor, most cells expressed microtubule-associated protein 2 and TUJ1, markers characterizing a post-mitotic neuronal phenotype as well as neural developmental markers Cdh2 and Gbx2. Real-time PCR was performed to determine the ionotrophic receptor subunit expression profile. Differentiated neural progenitors express subunits of glutamatergic, GABAergic, nicotinic, purinergic and transient receptor potential receptors. In addition, sodium and calcium channel subunits were also expressed. Functionally, virtually all the hNP cells tested under whole-cell voltage clamp exhibited delayed rectifier potassium channel currents and some differentiated cells exhibited tetrodotoxin-sensitive, voltage-dependent sodium channel current. Action potentials could also be elicited by current injection under whole-cell current clamp in a minority of cells. These results indicate that removing basic fibroblast growth factor from the neural progenitor cell cultures leads to a post-mitotic state, and has the capability to produce excitable cells that can generate action potentials, a landmark characteristic of a neuronal phenotype. This is the first report of an efficient and simple means of generating human neuronal cells for ionotrophic receptor assays and ultimately for electrically active human neural cell assays for drug discovery.

STEMEZ hN2 Cells-Electrophysiology Data

I will continue to post updates here.

In Search of Remyelination Therapies

Multiple Sclerosis (MS) is an inflammatory disease with no known cure. It affects over 400,000 people in the US and over 2.5 million people worldwide and is the leading cause of non-traumatic neurological disability in North America.

It is a chronic and brutal disease that attacks the brain and spinal cord. MS symptoms are due to the damage or loss of myelin sheath that surrounds, isolates and protects axons of brain and spinal cord. The results are often debilitating and afflict most sufferers in the prime of their lives. The annual costs to slow the disease and treat related
symptoms are in the billions of dollars and rising. There are currently no therapies to reverse damage of MS. At this point, there are only immune suppressive therapies that slow attack on the myelin sheath.

It is with hope and optimism that I present Dr. Satish Medicetty and his company, Renovo Neural Inc. (RNI) in this edition of the “News Behind the Neuroscience News”.

I became aware of Satish and his company in my search for Stem Cells that would broaden Neuromics ability to serve early phase Neuroscience Drug Discovery.

Satish Medicetty

Apr 2010 – Present: President and Board Director Renovo Neural Inc.

June 2008 – Mar 2010: Director of Stem Cell Research and Lab Operations
NeoStem Inc

July 2005 – June 2008: Senior Scientist Athersys

2006 – 2008: MBA, Case Western University

2002 – 2005: PhD, Kansas State University

After my first conversation with him, I was impressed with the capabilities RNI offered.

RNI

The company, founded in 2008 with a$3 million grant from the State of Ohio’s Third Frontier Commission, is leveraging cutting edge research from Dr. Bruce Trapp’s lab at the Cleveland Clinic.

At the core, RNI offers pioneering and propriety assays that give Drug Discovery Companies the ability to screen small molecules and compounds that could be lead therapy candidates for MS and other myelin-related diseases. These screens use a type of stem cell called adult oligodendrocyte precursor cells (OPCs).

The Power of OPCs

So what makes these OPCs an engine for finding cures for MS?  Inflammation associated with MS attacks destroys cells called oligodendrocytes that produce myelin. The only way to reverse this autoimmune related process is for the brain to produce healthy cells that can catalyze re-myelination. Enter OPCs.

OPCs are the raw material for processes the central nervous system uses to manufacture oligodendrocytes.  The brain’s inability to produce enough healthy cells to keep up with the destruction is a root cause of the disease. Understanding how to kick start and keep the oligodendrocyte factory running is a key to reversing this relentless destruction.

Delivering Value

RNI has the capabilities to the decrease time required and increase the odds for discovering potential MS therapies.  They have the raw material (OPCs) and the know how to encourage their transformation into myelinating cells. This expertise can be utilized can be used then to rapidly test new compounds both in vitro and in vivo.

In Vitro Assays Example

The features of their in vitro assays include:

• Stringent protocols to generate relatively homogeneous (>85% pure) and consistent population of OPCs as a reliable starting material for HCS assays
• Relatively high throughput primary screen to identify potential candidates that promote OPC proliferation and/or differentiation
• Secondary screen to confirm and qualify compounds for further pharmacological testing
• Positive and negative controls that demonstrate the utility of HCS assays to identify lead candidates that promote OPC proliferation and differentiation.

The features of their in vivo cuprizone assays include:

• Stringent protocols to generate highly reproducible demyelination/remyelination cuprizone model
• Cuprizone model recapitulates the in vivo process of demyelination and remyelination in the brain.
• Cuprizone model provides consistent and accurate results for key regions of the brain that are affected in MS patients including both white and gray matter regions – corpus callosum, hippocampus and cortex.
• Proof of concept studies demonstrate the utility of our in vivo remyelination assays to evaluate preclinical efficacy of potential remyelination therapies

The end goal is to discover therapies that repair neurons damaged by MS via remyelination and to get them in the hands of people that need them. I will keep you posted on their progress.

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!

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.