Weissmann C.,Scripps Florida |
Li J.,Scripps Florida |
Mahal S.P.,Scripps Florida |
Browning S.,Scripps Florida |
Browning S.,Cytonics Corporation
EMBO Reports | Year: 2011
Prions consist mainly, if not entirely, of PrP Sc, an aggregated conformer of the host protein PrP C. Prions come in different strains, all based on the same PrP C sequence, but differing in their conformations. The efficiency of prion transmission between species is usually low, but increases after serial transmission in the new host, suggesting a process involving mutation and selection. Even within the same species, the transfer of prions between cell types entails a selection of favoured 'substrains', and propagation of prions in the presence of an inhibitory drug can result in the appearance of drug-resistant prion populations. We propose that prion populations are comprised of a variety of conformers, constituting 'quasi-species', from which the one replicating most efficiently in a particular environment is selected. © 2011 Euroopeean Moleolecullar Bioloology Organnization. Source
Browning S.R.,Cytonics Corporation
The Journal of bone and joint surgery. American volume | Year: 2012
The effect of platelet-rich plasma on chondrocytes has been studied in cell and tissue culture. Less attention has been given to the effect of platelet-rich plasma on nonchondrocytic cell lineages within synovial joints, such as fibroblast-like synoviocytes, which produce cytokines and matrix metalloproteinases (MMPs) that mediate cartilage catabolism. The purpose of the present study was to determine the effect of platelet-rich plasma on cytokines and proteases produced by fibroblast-like synoviocytes. Platelet-rich plasma and platelet-poor plasma from harvested autologous blood were prepared with a commercially available system. Fibroblast-like synoviocytes were treated with platelet-rich plasma, platelet-poor plasma, recombinant PDGFββ (platelet-derived growth factor ββ), or phosphate-buffered saline solution and incubated at 37°C for forty-eight hours. The concentrations of IL-1β (interleukin-1β), IL-1RA (IL-1 receptor antagonist), IL-6, IFN-γ (interferon-γ), IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemotactic protein-1), MIP-1β (macrophage inflammatory protein-1β), PDGFββ, RANTES, TNF-α (tumor necrosis factor-α), VEGF (vascular endothelial growth factor), MMP-1, MMP-3, and MMP-9 in the culture medium were determined by multiplex immunoassay. Platelet-rich plasma cultured in medium contained multiple catabolic mediators in substantial concentrations, including MMP-9 (15.8 ± 2.3 ng/mL) and MMP-1 (2.5 ± 0.8 ng/mL), as well as proinflammatory mediators IL-1β, IL-6, IFN-γ, IP-10, MCP-1, MIP-1β, RANTES, and TNF-α in concentrations between 20 pg/mL and 20 ng/mL. Platelet-poor plasma contained significantly lower concentrations of these compounds. Platelet-rich plasma was used to treat human fibroblast-like synoviocytes, and the resulting concentrations of mediators were corrected for the concentrations in the platelet-rich plasma alone. Compared with untreated fibroblast-like synoviocytes, synoviocytes treated with platelet-rich plasma exhibited significantly greater levels of MMP-1 (363 ± 94.0 ng/mL, p = 0.018) and MMP-3 (278 ± 90.0 ng/mL, p = 0.018). In contrast, platelet-poor plasma had little effect on mediators secreted by the synoviocytes. PDGFββ-treated fibroblast-like synoviocytes exhibited a broad proinflammatory cytokine response at four and forty-eight hours. Platelet-rich plasma was shown to contain a mixture of anabolic and catabolic mediators. Synoviocytes treated with platelet-rich plasma responded with substantial MMP secretion, which may increase cartilage catabolism. Synoviocytes responded to PDGF with a substantial proinflammatory response. Source
Cytonics Corporation | Date: 2008-04-04
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.60M | Year: 2011
DESCRIPTION (provided by applicant): This is a proposal to collect the necessary data for FDA regulatory approval of the Cytonics assay as a diagnostic tool to identify patients who will respond to steroid injection therapy for LBP due to radiculopathy. Low back pain (LBP) syndromes include spinal degenerative conditions with and without nerve root or cauda equina irritation. These syndromes represent some of the most common reasons for patients to seek medical attention. LBP syndromes associated with neurological irritation are often effectively treated, whereas those not primarily associated with neurological irritation have proven resistant. The greatest current challenge in the clinical care of patients with LBP syndromes is identifying those who sufferfrom active neurological irritation and therefore may benefit from interventional therapies, such as corticosteroid injection (ESI). However, there is currently no validated test to discriminate between patients who will or will not respond to ESI. For example, only ~50% of the gt10 million yearly epidural steroid injections successfully relieve pain. Many patients that don't respond to initial steroid injections will receive follow-up injections at the same or a different spinal location. These unnecessaryinjections are costly and have side effects. In Phase I, we developed and validated an assay that can prospectively identify patients who will respond to steroid treatment. Our Specific Aim in Phase II is to collect the necessary data for FDA regulatory approval of the Cytonics assay as a diagnostic tool to identify patients who will respond to steroid injection therapy for LBP due to radiculopathy. To achieve this Objective, we will carry out the following Tasks: Task #1: Validate our assay to meet FDA manufacturing guidelines. Task #2: Carry out a large prospective study appropriate for obtaining PMA clearance using our validated assay. Task #3: Prepare and submit a PMA to the FDA. The assay will be sold as a kit, complete with all of the reagents required for the assay. We will provide the diagnostic kit to CLIA labs that are interested in providing the testing service, many of which will be located in surgical hospitals or outpatient centers. We will utilize a network of medical product distributors to provide information on the diagnostic to spine surgeons, neurologist, and pain management specialists in an effort to encourage the use of the test for their patients. We will also publish and present extensively on results of using our product. Phase II will result in a diagnostic assay to be submitted for FDA approval. PUBLIC HEALTH RELEVANCE: This is a project to develop a diagnostic assay that helps physicians know when to use steroid injections for treating back pain. Currently, 10 million such injections are made each year at a cost of about 2000 per injection. Half of the injections are ineffective. Our assay will allow physicians to know when a patient will not respond to an injection, thereby avoiding the needless injections and saving about10 billion dollars per year in ineffective treatments, as well as allowing the physician to focus on treating the patient more effectively.
Cytonics Corporation | Date: 2013-02-21
Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.