Sunday, March 5, 2017

Pain, Penile Erection, Panacea, in Poison Pillbox.


        Pain, Penile Erection, Panacea, in Poison Pillbox.          

 


Hunting Pain-Relief Drugs at a Marine Snail’s Pace

 This blog includes the recent note published http://www.chennaicitynews.net/news/hunting-pain-relief-drugsat-a-marine-snails-pace-by-dr-rao-v-l-papineni-40945/ and the potential of these cysteine scaffolds as pharma in Pain, Erectile Dysfunction, and aging related diseases.


Two recent news items brought back memories about my post-doctoral days in Baylor College of Medicine two decades ago. One directly associated with Tamilnadu that describes about the Irula Snake Hunters recruited for Python round-up at Miami Everglades https://www.washingtonpost.com/news/animalia/wp/2017/01/26/florida-is-deploying-snake-hunters-from-india-to-catch-invasive-pythons/?utm_term=.40fad59a62ad.  The other exciting news that appeared in innumerable news sites is about University of Utah’s finding of “Fish hunting Marine Conus Snail and its venom’s effect in Pain Management.  British Broadcasting Corporation BBC pointed out how the cone snail venom RG1A can be clinically used to treat chronic pain http://www.bbc.com/news/health-39028557.  These toxins can provide treatment with no side effects such as addiction which is common with morphine or other Pain relief drugs.  Globally, the Pain Management drug market is around 60 Billion US Dollars annually.
I started my post-doctoral research career at Baylor College of Medicine, Houston, working on these conotoxins.  This was in mid-90’s we made some seminal advances in this field primarily by thinking smarter that the Conus snail, producing modified version of toxin by chemical tinkering and by genetic manipulations using recombinant technologies ( Papineni et. al. J. Biol. Chem. 2002  http://www.jbc.org/content/276/26/23589.long).   The conus snails are found in the Philippines, Australia and Indonesia. The snail feeds on fish by injecting its venom using a harpoon like projectile from its mouth. The fish hunting process is so fast that the word “snail pace” gets a whole new meaning.  A link here https://www.youtube.com/watch?v=zcBmMPJrrKk will provide a glimpse of the weaponry, predator-prey mismatch. There are nearly 500 species of snail, and each one produce more than 100 different toxin molecules in its venom. These molecules are peptides, called Conotoxins, and its action in prey is by muscle paralysis.
Those were the exciting days, working with conotoxins, its pharmacology, very rewarding- note, it was a virgin territory.  Each chemical modification I made, and each recombinant toxin generated by
our collaborator in Puerto Rico Dr. Krishna Baksi, started providing tantalizing results.  It was all conotoxin in my life those days… During the finishing stages of the work, I invited Dr. Steen Pedersen, one of my many mentors in my life, for a brooski at BCM’s favorite watering-hole Gingerman.  My neighbor Arun who was there took the opportunity and started complaining to Steen about my incessant conotoxin related harangue during the course of that work.
Back in late 90’s, it was a taboo in academia to think of patents or commercialization. That view on patents rapidly changed by the turn of the century.  A patent on conotoxin was successfully filed in Utah by Dr. Baldomero Olivera.  It was nice to notice that work was duly cited in the USPTO patent. Dr. Olivera is a pioneer in conotoxins establishing a dedicated conotoxin laboratory in 1987. They determined the effect of Omega-conotoxin which specifically blocks neuronal voltage activated Ca++ channels and estimated to be 1,000 times more powerful than morphine. The drug was targeted to provide pain relief to patients with HIV and cancer.


Dr. Steen Pedersen and Dr. Rao Papineni at Biophysics Meeting, New Orleans 2000.


Along with Conotoxin, we worked on recombinant cobratoxins looking at ion channel structure-function.  The Miami Everglades Snake Hunters news item again made me look back at our two decade old research work on toxins and ion channel pharmacology.  Romulus Whitaker seen with Irula Snake Hunters is a world renowned herpetologists and founded the Madras Snake Park in my Hometown Madras.  A center, where Rom rehabilitated Irula Tribesmen in developing ant-venom drugs by extracting snake venom.  A haven for future toxin based Pain pharma. Utilizing the progress in Systems Pharmacology the past two decades, at PACT & Health, we are interested in harnessing the power of these cysteine scaffolds in Pain, Erectile Dysfunction, and anti-aging Drug Development.


Dr. Rao V. L. Papineni
Professor (Adjunct- assistant)
University of Kansas Medical Center KUMC
USA
Dr. Rao V. L. Papineni is an Adjunct faculty member at University of Kansas Medical Center, and a molecular theragnostics scientist at PXI, USA. He received his doctoral degree in Biochemistry from University of Hong Kong (British Terr). Dr. Papineni had his early education from University of Madras, where he earned his Bachelors and Master’s Degree. After ten years in Research and Faculty positions at University of Hong Kong and Baylor college of Medicine (USA), he joined Kodak/Carestream Health, USA.  Dr. Papineni has made several inventions and chaired scientific sessions in International Biomedical Meetings and serves on the editorial board of Nanotech and Experimental Pharmacology journals.  As a distinguished scientist, he initiated advanced research programs to study Inflammation and oncology utilizing molecular imaging and nanotechnology based molecular tools.  He recently identified and coined “Radiobioluminescence” a novel X-ray induced radiation phenomena that have immense potential in development of cancer therapeutic strategies.  His lab is instrumental in development of MIGRT  Molecular Image Guided Radiation Therapy technology and utilizing radiobiophotonics and MIGRT in Drug Discovery related to Cancer and radiation medicine.