“He said ‘this works to stop seizures,’ ” says Poulter, the director of the graduate neuroscience program at the school’s Robarts Research Institute.
“My first thought, of course, was ‘yeah, right, sure.’ ”
Since that May 2011 meeting, however, Nadeem Ashraf’s powdered elixir has proven to be the most promising epilepsy agent that Poulter has ever studied.
Indeed, its been so effective as an anticonvulsant in rat models, that Poulter recently launched a pharmaceutical startup to bring it towards human trials in as little as two years.
“It’s been very exciting for me … since this fellow arrived,” he laughs.
Ashraf’s pilgrimage to Poulter’s lab in London, Ont., originated the previous year with an emailed plea to come study his powder there as a graduate student. But Poulter, who has worked on epilepsy for two decades, never expected he’d actually show up.
“I must get four or five emails a week from people around the world who say they want to come and work in my lab,” he says.
Strapped for funding himself, however, Poulter tells most of the applicants that they’d be welcome so long as they could scrape together enough money in their home countries to provide their own financing.
And it usually ends there.
“But about six or eight months later (Ashraf) emailed again and said he’d gotten money from the Institute of Higher Education in Pakistan … and that he was going to be here.”
What Ashraf brought with him was a root extract from a small, lavender- colored flower — the Delphinium Denudatum — that grows wild in the outer ranges of the western Himalayas.
There, Ashraf says, the plant’s crushed roots have been brewed into a tea that’s been used for centuries as a folk remedy to control seizures.
“It grows on grassy slopes in western regions of the Himalayas and Kashmir at a high altitude of around 10,000 to 12,000 feet above sea level.” Ashraf said in an email interview.
Now an assistant pharmacy professor at Pakistan’s Islamia University of Bahawalpur, Ashraf says parts of the plant have also been used to treat everything from facial palsy and paralysis to brain and nerve poisonings.
He had been studying the plant’s anti-epilepsy properties for several years before he met Poulter, and had helped to isolate its active ingredient.
Ashraf says, he wanted to bring that isolated molecule to Western, where he’d be better able to investigate its effects on various epileptic conditions.
Poulter says that active agent is a small molecule known as isoxylitone, for which his OB Pharmaceuticals startup has obtained a patent to license as ISOX.
Having further isolated and purified the compound, Poulter’s team then administered it to the London lab’s rat models, which were engineered to go into epileptic spasms when stimulated electronically.
“And much to my surprise … the majority of the animals that we treated with this drug, we could not get them to become epileptic,” Poulter says.
“That was what really got us quite excited because drugs that stop the genesis of the seizures are exceedingly rare, and I would guess there aren’t any.”
Poulter’s research on the Himalayan molecule was enticing enough to attract financial support from the Ontario Brain Institute, a provincially backed body that helps navigate potential medicinal breakthroughs to human trials and beyond.
University of Toronto pharmacologist McIntyre Burnham, co-leader of the institute’s epilepsy program, says Poulter’s startup will receive at least $132,000 for two years, with the possibility of three further years of support if results warrant it.
Burnham says it’s typical in new drug development for university researchers to form a company to develop their compounds through to human trials and to seek funding from the institute and other sources.
Currently his organization is helping to finance animal studies on three epilepsy drugs, each of which have earned a “promising” label from Burnham.
Poulter says he and several colleagues have also poured some of their own money into the company.
As with any therapeutic compound that has yet to be tested on humans, Poulter offers the usual and altogether proper caveats about isoxylitone.
Key among these are that it may not be usefully absorbed by the far more complex human biological system and that the side effects that will accompany any medication could outweigh its therapeutic value.
“I don’t want to oversell this,” Poulter says.
“It’s really hard to predict, once you put the molecule into hundreds of thousands of people, what kind of side effects are going to pop out.”
But so far, Poulter says, he’s seen no evidence in his rats of the sluggishness and muscle stiffness that current epilepsy drugs often cause.
And the knowledge that it’s been used for centuries in traditional Himalayan medicine gives him greater hope that it will be well tolerated and effective in human patients.
Dr. Peter Carlen, head of the Toronto Western Research Institute’s fundamental neurobiology division, agrees that its previous and anecdotally effective use in Himalayan populations increases the compound’s chances of becoming an approved drug in the West.
“Absolutely, why not,” says Carlen, also a neurologist in the University Health Network’s epilepsy program. “I think that (folk medicine use) is fine, it certainly doesn’t hurt it.”
And Carlen — who has consulted for Poulter, but has received no money from his company — says isoxylitone “certainly shows great potential” as an anti-epileptic drug.
“It seems to be in animal studies … quite non-toxic and it’s very effective as an anti-convulsant,” he says.
Epilepsy is a spasmatic disorder that’s triggered by haywire bouts of electrical activity in the brain. It can have a host of different causes, including head injury and genetic defects.
It can also have a cumulative severity, with each seizure increasing the frequency or intensity of the ones that follow, Poulter says.
That’s one reason, he says, that the new chemical has generated so much excitement in his lab and elsewhere.
“There doesn’t seem to be any medication that can stop that (progression), and what we’re seeing with this molecule is it seems to stop that,” he says.
A 2013 paper published in the Journal of Neurochemistry showed the drug could prevent the “kindling” of even one seizure, meaning the severity spiral might be avoided altogether.
The paper also postulated the basic mechanism of the drug, which works by blocking a sodium-based chain reaction in the brain.
This sodium chain runs amuck in epileptics, eventually triggering the creation of a brain protein known as BDNF, which appears to fire the ailment’s convulsive fits.
While other epileptic medications also act on the sodium channel, Poulter’s compound appears to do it at an earlier stage in the cascade and at a smaller dosage.
If it works at low dosages in humans, the side effects that often accompany epileptic medications could be minimized.
As well, Poulter says that 30 per cent of epileptics do not respond to any current drugs and that any new medication could help to close that drug gap.
Source: Metro News