Headline July 21, 2017/ ''' PAINS... \ PUNS / ...PARSE '''

''' PAINS... \ PUNS / ...PARSE '''

*GLOBAL ELECTIONS   AT   PROUD PAKISTAN*      -the first conceptual host and sacred  trustee of the World Students Society,    l Task,,,,,,,, :

Student Engineer Wajahat Raja / University of Aberdeen, Scotland,  Student Umer Khan, Architect Furqan/MS Spain, Student Awais K, and-

Teacher and coach- Zara [Pakistan's Women Football team] to gradually and professionally  help set up the   psychological base   and coordination hub,  and public communications node, to enable Faraz and Ali to operate.

!WOW!  -the World Students Society belongs to every single student of Pakistan, One Share-Peace-Piece-  just as it belongs to every single student in the World  : One Share-Peace-Piece.

*Time to get  radical  about  joining up, and see for yourself : How Pain Works through and through*   And great Time for  you all to build a great model for the entire world,  to look at.

Clear?   :    Faraz, Ali, Umer, Wajahat, Furqan, Zilli, Zara, Saima, Sanyia, Dantini/Malaysia, Lakshmi/India, Zainab/ Hong Kong?       

FOLLOWING NEWS REPORTS   and word of mouth, Xenon tracked down and studied 12 families around the world with insensitivity to pain. [The Petes were not among them. Outside their immediate community, few people knew about the brothers condition].

For Sherrington, it was incredible that these individuals and and their genomes existed. Evolution should have weeded out most of their ancestors. ''Feeling pain is protective,'' Sherrington says. ''They would not have felt certain noxious stimuli. They should not have survived.''

By studying those 12 families genomes throughout 2001 and 2002, Xenon found a common trait among those with insensitivity to pain; mutations in a single gene, SCN9A, and the malfunctioning sodium channel it encodes, Nav1.7.

''This single channel, when it is nonfunctioning in a human being, renders them unable to understand or feel any form of pain,''  Sherrington says, summarizing the team's initial findings.

And of  Xenon  could develop a new drug that could somehow mimic this condition   -''to inhibit the Nav1.7 channel to partially replicate the absence of pain,'' he explains  -then it could relieve people's pain without any of the side effects of opioids.

It is rare for biology to deliver such a seamless positive-negative effect within a single gene. In man on fire patients, one SCN9A mutation leads to a hyperactive Nav1.7 channel, which causes extreme discomfort.

In those with  insensitivity to pain, another  SCN9A mutation leads to an inactive Nav1.7 channel, which results in total numbness. 

Given that the teams at Xenon and Yale were working on opposite coasts, and on conditions that fell on opposite sides of the pain spectrum, they only learned of each other's discoveries through published reports and journal articles.

[Sherrington first learned about Waxman's study at Yale in 2004' Waxman only read about Sherrington's work at Xenon after the company published its results in 2007]. 

Both teams arrived at the same clinical destination from a totally different direction, surprised as anyone that people like  Pam Costa and Steven Pete had anything in common.

''I was overwhelmed when we saw both sides of the genetic coin,'' Waxman remembers. ''SCN9A really is a master gene for pain.''

Not long after their discovery, technicians at  Xenon set to work putting Nav1.7 channels into tissue cultures, then testing each a compound from their vast library of molecules.

They were looking for a blocker that would shut off or at least turn down the faucet on Nav1.7 without affecting the body's other eight sodium channels. 

*If you block Nav1,4, for example, you might block muscle movement. Blocking Nav1.5  can inhibit the heart. Blocking Nav1.6   might impact the brain, causing double vision, confusion, balance problems, or even seizures*.

One by one, they experimented with thousands of combinations until they got a hit   -a compound that plugs up Nav1.7 without major side effects. From that, researchers then created a drug called  TV-45070 and conducted pilot tests on four erythromelalgia patients.

In three of the four,  ''these individuals''   pain responses were markedly blunted, and in case we couldn't elicit pain at all,'' says Simon Pimstone, president and CEO of Xenon. Now TV-45070 is being used in Phase 2 clinical trial on 330 patients who suffer from nerve pain.

As for Waxman, he and his researchers at Yale helped Pfizer test five eythromelalgia patients with another Nav1.7 blocker. Scientists triggered the subjects' pain with heating blankets and asked them to rate their feelings before and after taking the drug.

Last year  Pfizer and Waxman's team reported that three of the five patients described a decrease in pain with the blockers.

There are other, less conventional approaches under way too. At Amgen, a pharmaceutical company in  Thousand Oaks , California, scientists test up to 10,000  molecules against Nav1.7 each week.

In 2012 they discovered that the toxin of  Chilean tarantula can target Nav1.7 with minimal impact on their sodium channels. They're since engineered a synthetic version of the spider's toxin that's more potent the original.

These findings, while significant, are still small step forward. 

Over the past few years, with larger pools of patients suffering from arthritis, sciatica, shingles, and many other kinds of pain, researchers will continue to test the practical applications of these discoveries.

''At least half a dozen companies are trying to  sodium channel blockers  that preferentially or selectively block 1.7,''  Waxman says. And while obstacles remain   -ensuring that only the Nav1.7  channel is affected. creating compounds-

That will allow some pain to register without cutting it off altogether; surviving the rigors of  FDA approval  -he and many others see a way forward.     

The Honour and Serving   of the latest  Operational Research  for awareness, research and use,  all in the service of Humankind continues.

With respectful dedication to the Research Scientists, Hospitals, Students, Professors and Teachers of the World. See Ya all on !WOW!   -the World Students Society and Twitter-!E-WOW!   -the Ecosystem 2011:

''' !WOW! & !WOW! '''

Good Night and God Bless

SAM Daily Times - the Voice of the Voiceless


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