Tuesday, June 24, 2014

More Gains on Pain Research

Discovering the Related Pathways

There are multiple descriptions for chronic and acute pain: stabbing, burning, cutting, itching, numbing, crushing and more. Understanding the pathways are important to optimizing the therapies and treatments for the many different forms of pain.

The foundation of Neuromics is providing top notch pain research markers, gene expression analysis tools and cell based assays. Here I share recent publications from customers using these:
Inflammatory Joint Pain: Fiona B Carr, Sandrine M Géranton and Stephen P Hunt. Descending controls modulate inflammatory joint pain and regulate CXC chemokine and iNOS expression in the dorsal horn. Molecular Pain 2014, 10:39 doi:10.1186/1744-8069-10-39...mu opioid receptor, 1:10,000, Neuromics (RA10104)...

Images: Representative single plane confocal images of MOR immunohistochemistry in the 1.5pmole dermorphin-saporin group and saline control. Double labelling with NeuN indicated that although many MOR+ neurons are depleted at this dose, some surviving MOR- neurons remain in the region, indicated by white arrows. Scale bars indicate 25 µm

Temperature Sensation: Marics I, Malapert P, Reynders A, Gaillard S, Moqrich A (2014) Acute Heat-Evoked Temperature Sensation Is Impaired but Not Abolished in Mice Lacking TRPV1 and TRPV3 Channels. PLoS ONE 9(6): e99828. doi:10.1371/journal.pone.0099828. ...TRPV1 antibody (1/1000 dilution, Neuromics)...

Acute PainPaulino Barragán-Iglesias, Hector I. Rocha-González, Jorge Baruch Pineda-Farias, Janet Murbartián, Beatriz Godínez-Chaparro, Peter S. Reinach, Thiago M. Cunha, Fernando Q. Cunha, Vinicio Granados-Soto, Inhibition of peripheral anion exchanger 3 decreases formalin-induced pain, European Journal of Pharmacology, Available online 27 May 2014, ISSN 0014-2999, http://dx.doi.org/10.1016/j.ejphar.2014.05.029. (http://www.sciencedirect.com/science/article/pii/S0014299914003914). ...substance P (guinea pig; 1:200; Cat # GP14110; Neuromics, Edina, MN), and purinergic P2×3 receptor (guinea pig: 1:1000; Cat # GP10108 ...

We are pleased with the many publications and customer provided data proving the quality of our many pain research tools. I am always available to serve you, Pete Shuster (pshuster@neuromics.com) or direct phone: 612-801-1007.

Sunday, June 15, 2014

Neuromics-Vitro Biopharma in Posrche Cup

Racing to Health and Peak Performance.

Neuromics and Vitro Biopharma are proud sponsors of the European Porsche Cup Car driven by our partner, friend and race car driver extraordinaire, Dr. Joe Smarda.
Dr. Smarda, an applied immunologist, is our partner in Europe for testing and treating sufferers of autoimmune diseases, sports injuries and autism with Stem Cell Activators. We are also testing these activating agents for the ability to improve the mental acuity and physical performance of healthy individuals.

He recently won a race at the Nurbring Ring in Germany. Hmmm, I wonder if the Stem Cell Activators he is taking, helped? Stay tuned.

Saturday, June 07, 2014

Stem Cell Therapies without Transplants

Neuromics is partnering with Vitro Biopharma to develop stem cell activating/boosting therapies. 

Stem cell based therapies represent a shining light of hope for sufferers of chronic or life threatening diseases.  Though, for most, realization of this hope is light years into the future.

Dr. Jim Musick, CEO of Vitrobiopharma, recently blogged on the obstacles to approved therapies : "Transplantation of hematopoietic stem cells has been widely used as an approved treatment of leukemia, lymphoma and certain autoimmune conditions for the past fifty years. Other adult stem cells have demonstrated safety and efficacy in pre-clinical research and clinical trials. Mesenchymal stem cell transplants have been most widely studied in animals, especially horses and dogs. Many of these studies have focused on skeletal-muscular effects. There is significant support for safety and efficacy in osteoarthritis, including cartilage regeneration, pain and inflammation reduction as well as recovery of function using intra-articular MSC injections (1). There are fewer studies of neural stem cell and Satellite cell transplants, but these also suggest safety and efficacy in various conditions. There are minimal adverse effects of these stem cell transplants

However, there are significant obstacles to routine clinical use of non-hematopoietic adult stem cell transplantation. First, therapeutic effect is dependent on cell concentration and exhibits characteristic dose-response relationships, necessitating expansion and characterization of MSCs prior to transplantation. While MSCs readily proliferate in vitro, this may result in cellular/genetic modifications and the cell culture conditions necessary for expansion of clinical grade MSCs have not yet been determined. Autologous sources appear superior to allogeneic, but controlled expansion of autologous MSCs could be limited. Also, there are regulatory obstacles including the US FDA that considers expanded stem cells “altered” with associated regulatory burdens prior to approval. Thus, it is likely that MSC transplantation has a long and expensive pathway to attain routine clinical implementation."

We are in the process of developing a new paradigm.
Images: UCB Derived hMSCs Activation Assays

The development of this new model includes assays that enable us to determine optimal dosing for these activators (see above).  Here's more from Dr. Musick: "Stem cell activation awakens innate stem cell systems to optimize healing, cellular regeneration and functionality. This approach has numerous advantages over stem cell transplantation including innately autologous therapy without acute or long-term complications from introduction of allogeneic cellular materials. The approach involves administration of an activating agent or agents and effects are controlled by dosage/pharmacokinetics of the stem cell mobilizing, epigenetic or proliferative agents thus avoiding transplantation issues including possible cellular modification during expansion, contamination, etc. The pathway to regulatory approval is shorter and less costly since certain combinations of generic drugs may be effective and there are natural substances exhibiting apparent efficacy. Also, new drug targets are associated with this paradigm, such as specific combinations of proliferation and epigenetic agents.

Vitro Biopharma has been pursuing this approach for the past six months using patients treated within a clinical network. The primary approach is to resolve toxicity, infectivity and specific deficiencies thus restoring physiological conditions while monitoring clinical status. Optimum cellular functionality is viewed as a necessary condition to elicit therapeutic benefit from activation of endogenous stem cells. We also use proteomic arrays to quantify various cytokines, growth factors and neurotrophins to develop disease profiles. We establish baseline results and are now testing agents known to activate stem cells to determine effects on the biomarker disease profile as well as clinical status. We are also developing additional biometric analysis of stem cell activation including MSC mobilization to peripheral blood, serum content of key stem cell biomarkers and tools for imaging of stem cell activation.

Vitro Biopharma is nearing commercialization of stem cell-based assays utilizing live cell imaging of cell migration, proliferation and reprogramming for drug discovery and support of clinical trials. We are also developing a clinical trial testing of stem cell activation for treatment of TBI and advanced molecular diagnostics while developing new stem cell activators. Vitro Biopharma is committed to further development and testing of the activation of latent, internal stem cells since this approach is widely supported by pre-clinical research and obviates several problematic issues associated with the transplantation of adult stem cells."

I will continue post here developments with our exciting, new approach to stem cell related therapies.

References: 1. Jo, CH. et al., Stem Cells 32: 1254-1266, 2014 2. Sinha, M. et al., Science 344: 649, 2014