Multiple Sclerosis (MS) and Sleep

Tuck is an excellent resource for people who suffer from sleep disorders. That said, we all can gain from better sleep so if you are looking to improve your sleep by making changes, Tuck has great content to help you optimize your sleep-related decisions.

Tuck has expertise on MS and Sleep. As if the disease isn’t insidious enough, it is often accompanied by disrupted sleep. These range from insomnia to its opposite hypersomnia.

If you or someone you love has the combination MS and sleep disorders, Tuck can help. You can start by checking out MS and Sleep.

Gerry Shaw-Master of World Class Neuronal/Glial Markers

Build it and They will Come

Gerry and One of His Triumph's MCs
Gerry and One of His Triumph’s MCs

I am pleased to profile Dr. Gerry Shaw, a Professor at the University of Florida and also the Head of EnCor Biotechnology Inc.  His story is a guide for incubating and spinning out a successful biotech company (EnCor Biotechnology, Inc.) from a university research laboratory. It should provide an inspiration for fledgling entrepreneurs as the model required little capital investment and has enjoyed profitable growth.

The Backstory

Gerry’s major area of research interest can be summarized as the study of cellular changes resulting from central nervous system damage and disease states. These changes help neuroscience researchers understand the progression and hopefully discover root causes of diseases like Alzheimer’s, Parkinson’s and ALS. Understanding which proteins are involved in particular disease states also has the potential of identifying targets for therapies.

The story starts with Gerry’s Post Doctoral research at the Max Planck Institute for Biophysical Chemistry in Goettingen, in what was at the time West Germany. Here he joined the world renowned laboratory of Klaus Weber and Mary Osborn. This lab had pioneering several important techniques, notably SDS-PAGE for protein analysis and the use of antibodies in immunocytochemistry. Later, after Gerry left the same lab made key contributions leading to the routine use of RNAi in “knock down” of normal cellular proteins. The lab had developed antibodies to tag the subunit proteins of microtubules, microfilaments, intermediate filaments and other cellular proteins, and then used these antibodies to visualize the proteins in immunofluorescence microscopy and on western blots. This enabled researchers to look at changes in the cellular expression of these proteins in powerful new way. These methods have become vital tools for understanding normal cellular function and what happens when cells transition from healthy to diseased states. This lab was an ideal location for Gerry to learn how to make quality monoclonal and polyclonal antibodies. Good antibody reagents are vital for the correct interpretation of immunofluorescence microscopy and western blots, and he was soon supplying his reagents to friends, collaborators and other researchers all around the world. Success is value as antibodies that do not as work as expected waste research time and resources, while quality reagents soon become appreciated and may get to be standard lab reagents.

University of Florida

The University of Florida, in Gainesville imported his expertise when Gerry joined the institute in 1986. Here he continued to make antibodies to Neurofilaments or NFs and other Neuronal-Glial Markers. It’s hard to keep a good thing a secret and Gerry faced growing demand from all over for these reagents. This proved a drain both financially and in terms of time commitment, as well as a significant conflict of interest with his basic biomedical research program.

MAP2_Doering IHC Image: Co-culture of embryonic mouse hippocampal neurons and astrocytes. Primary embryonic hippocampal neurons at 7 days in vitro, were stained with Microtubule Associated Protein-2 (MAP, green) to enable the visualization of the dendritic arbors. These neurons were cultured on top of a monolayer of primary cortical astrocytes, stained with an antibody directed against

Glial Fibrillary Acidic Protein (GFAP, red). The cell nuclei were visualized by staining with 4′,6-diamidino-2-phenylindole (DAPI, blue). BMC Image of the Month October 2010

As a result Gerry took his first entrepreneurial step by selling his most popular reagents in bulk initially to Chemicon (now Millipore-Merck). Like any new business venture, he did not really know what to expect. It should come as no surprise that the reagents sold like hot cakes and the check started rolling in. Other immunoreagent companies approached Gerry and soon he was supplying antibodies to pretty much every major biotechnology vendor.

ABC Biologicals to EnCor Biotechnology Inc.

Success breeds success and as sales increased over the 1990s, it was time to form an independent business and so ABC Biologicals Inc. was incorporated in 1999 initially to buy equipment and develop licensing agreements. Since Gerry had income from sales, he was in the unusual and enviable position of not needing grants, investors, loans or cash from any other source, and so could proceed with almost total independence. The company was renamed EnCor Biotechnology Inc. in 2002, and at the same time moved into the Sid Martin Biotechnology Incubator, a lab dedicated to commercialization of intellectual property generated by the faculty of the University of Florida. The University of Florida is unusually experienced at this and is well known for launching Gatorade, Trusopt and many other products. After 4 years EnCor “graduated” from the Incubator and now occupies a facility in Gainesville. The company now has almost 100 products with many more under development. This is good news for the Neuroscience community.

The EnCor-Neuromics Connection

Neuromics provides EnCor Biotechnology reagents to researchers studying neuro-degeneration, neuro-regeneration, neuro-development, neural stem cells, mood disorders, brain injury and spinal cord injury. My customers have found EnCor’s reagents to be rock solid and versatile.

In addition, Gerry and his team have proved adept at culturing our E18 hippocampal neurons and ESC derived hN2TM primary neurons. This is a big plus as we can actually see how the cells and markers could resonate together for use in cell based assays.

Hippo_MAPT_DC1 Image: E18 hippocampal neurons stained with Tau (red) and Doublecortin (green). The two proteins overlap in the proximal dendrites (yellow) Axons (low doublecortin content) are red. Blue staining is the nuclear DNA.

Futures

I am excited by the glimpse of the future that Gerry shared. We can expect many new, novel and important markers in the coming months and years. In addition, he will be manufacturing various Enzyme-linked immunosorbent assays (ELISA). These kits have the potential to help clinicians diagnose the early onset of diseases like ALS, Parkinson’s and Alzheimer’s.

For example, his company currently sells an ELISA kit for sensitive detection of Phosphorylated Neurofilament-H (pNF-H). Expression of this protein is up regulated in a variety of damage and disease states, and can be used to accurately quantify this up regulation. The kit can also detect pNF-H in the sera and spinal cord fluid (CSF) of animals with spinal cord and brain lesions. This protein is not normally found in sera or CSF, so its presence indicates recent axonal injury as a result of either damage or disease. This suggests pNF-H is a useful biomarker of neuronal and more specifically axonal injury or degeneration, a suggestion supported by a growing list of basic science publications on various animal models and patient types from Gerry’s research lab (e.g. Shaw et al. 2005, Lewis et al. 2008, Boylan et al. 2009, Lewis et al. 2010).

Given the capabilities of EnCor’s markers, the development of more kits is coming. There could be a day in the not distant future where they give clinicians tools to better diagnose and monitor serious neurodegenerative diseases, leading to better disease treatment and management.

I will keep you informed on Gerry’s and EnCor’s future developments.

Satish Medicetty-Platforms for MS Drug Discovery

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

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 Vito Assays Example

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.