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.
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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.