Delivering drug straight to the brain could cut required dose by as much as 75 per cent — ScienceDaily


A team of neuroscientists and engineers at McMaster University has created a nasal spray to deliver antipsychotic medication directly to the brain instead of having it pass through the body.

The leap in efficiency means patients with schizophrenia, bipolar disorder and other conditions could see their doses of powerful antipsychotic medications cut by as much as three quarters, which is expected to spare them from sometimes-debilitating side effects while also significantly reducing the frequency of required treatment.

The new method delivers medication in a spray that reaches the brain directly through the nose, offering patients greater ease of use and the promise of improved quality of life, including more reliable, effective treatment.

Ram Mishra, a Professor in the Department of Psychiatry and Behavioural Neurosciences and Co-Director of McMaster’s School of Biomedical Engineering, and Todd Hoare, a Canada Research Chair and Professor of Chemical Engineering, describe their research in a newly published article in the Journal of Controlled Release.

They and their co-authors Michael Majcher, Ali Babar, Andrew Lofts, and Fahed Abuhijleh have proven the concept of their new delivery mechanism in rats, using PAOPA, a drug commonly prescribed to treat schizophrenia.

A problem for patients using antipsychotic medications, Mishra explains, is that taking them orally or by injection means the drugs must pass through the body before they reach the brain through the blood. To be sure enough oral or injected medication reaches the brain, a patient must take much more than the brain will ultimately receive, leading to sometimes serious adverse side effects, including weight gain, diabetes, drug-induced movement disorders and organ damage over the long term.

When delivered through the nose, the spray medication can enter the brain directly via the olfactory nerve.

“The trick here is to administer the drug through the back door to the brain, since the front door is sealed so tightly,” Mishra says. “This way we can bypass the blood-brain barrier. By delivering the drug directly to the target, we can avoid side effects below the brain.”

Mishra and collaborator Rodney Johnson of the University of Minnesota had previously created a water-soluble form of the medication, which was used in the current research. The new form they created was easier to manipulate, but they still lacked an effective vehicle for getting it to the brain. A particular issue was that drugs delivered via the nose are typically cleared from the body quickly, requiring frequent re-administration.

Hoare, in the meantime, had been working with an industrial partner to develop the use microscopic nanoparticles of corn starch for agricultural applications.

The two scientists, who work across campus from one another, came together after researchers in their labs met at an internal McMaster conference. Two of the researchers, Babar and Lofts, worked on the project in both labs.

The engineering team was able to bind the drug to the corn starch nanoparticles that, when sprayed together with a natural polymer derived from crabs, could penetrate deep into the nasal cavity and form a thin gel in the mucus lining, slowly releasing a controlled dose of the drug, which remains effective for treating schizophrenia symptoms over three days.

“The cornstarch nanoparticles we were using for an industrial application were the perfect vehicle,” Hoare says. “They are naturally derived, they break down over time into simple sugars, and we need to do very little chemistry on them to make this technology work, so they are great candidates for biological uses like this.”

The gradual release means patients would only need to take their medication every few days instead of every day or, in some cases, every few hours.

The research work was funded by a Collaborative Health Research Partnership Grant (from the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research) and McMaster University’s Interdisciplinary Research Fund.

The researchers are seeking a corporate partner to move the technology into the marketplace.

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Jockey Noel Callow shown tweets of alleged drinking and drug abuse before riding at Kilmore


Five-time Group 1-winning jockey Noel Callow was left in shock when shown texts of alleged drinking and drug use by stewards prior to riding a hot favourite at Kilmore.

A Twitter handle with just 38 followers sparked a heated stewards inquiry involving jockey Noel Callow before he rode $1.70 favourite Diamonds’n’stones to win at Kilmore on Tuesday.

Callow was at Kilmore for just one ride, the hot elect for Team Hawkes in the second race, when he was asked to provide a random urine sample under the normal drug testing procedure.

But it was the subsequent inquiry into an unsubstantiated “tweet”, responding to the official Racing Victoria stewards Twitter handle on an unrelated matter that raised the jockey’s ire as he prepared to ride the favourite.

The tweet, shown to Callow as a screen shot by stewards, alleged he was seen at a Richmond hotel on Monday “Had 100 pints last night 2 bags, last seen at the sporting globe Richmond claiming not to be Noel Callow”.

It followed another tweet response to Racing Victoria stewards from the same account that alleged Callow had “40 pints and a (picture of a bag) and can no longer ride”.

“I was absolutely stunned,” Callow told Racenet.

“I thought this couldn’t be serious, it rattled me.

“I’m self-employed, I’m there to do a job for my owners who employ me and the trainers. It’s a privilege to ride for John Hawkes and his family and after all that happened I’m behind the barriers thinking this isn’t happening. Thankfully the race couldn’t have gone any better and the horse won like he should have.”

“I arrived at the races early and had a sauna before being told my number was up for a random drug test. I have no problem with that, I had to drink a little water so I could provide a sample.

“I know the stewards have a job to do and absolutely no problem with the drug test, they happen all the time. But it was when stewards called me to the room to talk about the tweet and its allegations that shocked me. I thought ‘are they serious’.”

Callow was then asked to do a breath test, which he agreed to in the jockey’s room within 45 minutes of the race start time. It came back negative.

Callow, who objected to being asked personal questions about his whereabouts on Monday after the allegations were tabled, told stewards he had spent Monday watching American NFL football with fellow jockey Mark Zahra.

“I’m not on social media but it’s disappointing and frustrating that I have to answer these sort of allegations from someone with no credibility.” Callow said.

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Mesoblast holds out hope for heart failure drug


Shares in stem cell biotech Mesoblast jumped nearly 16 per cent after the company said it would pursue approval for its key heart failure drug in the US despite a clinical trial delivering mixed results.

On Monday the company told investors that additional data from the phase 3 trial of its Revascor product showed a “substantial and durable reductions in heart attacks, strokes and cardiac deaths” in patients with chronic heart failure.

Mesoblast shares bounced after a tough end to 2020, when shares were savaged after news its COVID-19 trial was unsuccessful.

The company had trialled Revascor on 537 patients with advanced chronic heart failure and it showed a reduction in mortality rates for heart failure patients. However, last December Mesoblast revealed this trial was unsuccessful in meeting its main stated aim: showing the drug reduced the incidence of trips to hospital for non-fatal heart failure events.

On Monday, the company released updated data from this study to the ASX, arguing that despite missing its main goal in regards to hospitalisations, the research suggested the drug could help reduce deaths of patients where there are few other treatment options.

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Honduras president took bribes from drug traffickers, US prosecutors claim


He has said that traffickers are falsely accusing him to seek vengeance for clamping down on them.

Honduras’ ambassador to the United States, Luis Fernando Suazo, on Saturday rejected the new filings, calling the prosecutors’ contentions “baseless” and reiterating the president’s position that they are based solely on statements from self-confessed drug traffickers.

Honduras’ President Juan Orlando Hernandez with US Vice-President Mike Pence in 2017.Credit:AP

“They’re the ones who have reason to get revenge, they’re the ones who have reason to reduce their sentences, those are the sources,” the ambassador said. “Why don’t we see other types of witnesses, other types of evidence?”

The motions seek pretrial approval to admit evidence in the case of Geovanny Fuentes Ramírez, who was arrested in Miami in March. And they expand upon allegations filed shortly after the arrest accusing Hernandez of taking bribes in exchange for protection from law enforcement.

Fuentes Ramirez is accused of conspiring to smuggle cocaine into the United States and the motions filed on Friday accuse him of producing “hundreds of kilograms a month” of cocaine and of having several people killed to protect his illicit business.

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“By late 2013, the defendant partnered directly with CC-4 and high-ranking officials in the Honduran military. At this time, CC-4 was pursuing election as the President of Honduras as a member of the Partido Nacional de Honduras (the “National Party”),” the motion said.

It added that a witness “would testify that that they and other drug-traffickers were paying massive bribes to CC-4 in exchange for protection from law enforcement and extradition to the United States;” and that the president-to-be “accepted approximately $US1 million in drug trafficking proceeds that was provided to his brother by the former leader of the Sinaloa Cartel, Joaquín Guzmán Loera.”

Prosecutors say he had agreed to work through the president’s now-convicted brother.

The motions also implicate senior military, police, political and business figures in laundering money and bribery.

Hernandez, who had been president of congress before being elected president in 2013, was reelected in 2017 to a term that ends in January 2022. He has co-operated with the Trump administration and its efforts to stem migration from his nation and others in Central America.

During a January 2020 visit to Honduras, acting US Department of Homeland Security Secretary Chad Wolf said, “Honduras is a valued and proven partner to the United States in managing migration and promoting security and prosperity in Central America.”

AP

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Motorcyclist dies in crash near Mannum, while Norwood pair are charged over drug and firearm offences


A man in his 30s has died after crashing his motorcycle about 80 kilometres east of Adelaide.

Just before 6:00am on Saturday, a motorist driving along Randell Road, just west of Mannum, came across the crashed motorcycle.

Authorities pronounced the rider, a 36-year-old man from Mount Barker, dead at the scene.

His death takes South Australia’s road toll for 2021 to five, compared to just one at this time last year.

Randell Road was closed on Saturday morning but expected to reopen in the afternoon after major crash officers investigated the scene.

SA Police have urged anyone who drove through the area last night and saw anything that may assist the investigation to contact Crime Stoppers.

Pair arrested, charged after city pursuit

Meanwhile, a man and woman were arrested and charged with a raft of offences — including possessing a firearm — following a police pursuit through Adelaide on Friday night.

Just after 9:00pm on Friday, a police patrol stopped a black BMW sedan on Grenfell Street, Adelaide, for a routine traffic stop.

Officers were checking the male driver’s licence, which appeared to be fake, when the car took off.

It drove through several red lights in the city and travelled the wrong way around the Britannia roundabout in heavy traffic.

The police helicopter located the car abandoned in a hotel car park on Regent Street in the CBD before police found and arrested the man and woman at a house on Church Avenue at Norwood.

Methamphetamines and an imitation firearm were found during a search of the property.

The man, a 32-year-old from Norwood, was charged with dangerous driving to escape police, trafficking a controlled drug and possessing a firearm without a licence.

The woman, a 23-year-old also from Norwood, was charged with trafficking a controlled drug, possessing a firearm without a licence and hindering police.

The pair were refused bail and will appear in the Adelaide Magistrates Court on Monday.

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Dayana Yastremska doping positive, male fertility drug, response


Ukraine tennis star Dayana Yastremska was suspended on Friday after testing positive for a banned anabolic agent used in male infertility treatment with the world number 29 insisting she was “astonished and shocked” by the result.

The International Tennis Federation (ITF) said Yastremska was positive for the banned mesterolone metabolite in an out-of-competition test conducted last November.

“I firmly state that I have never used any performance enhancing drugs or prohibited substances,” Yastremska said on Twitter.

“I’m astonished and under shock, particularly given that two weeks prior to this test on November 9, I tested negative at the WTA event in Linz.

“Only a very low concentration of mesterolone metabolite was detected in my urine. Given that low concentration and given my negative test two weeks earlier, I have received scientific advice that the result is consistent with some form of contamination event.

“Besides I have been informed that this substance is meant to be used as medication by men and women are advised not to use it due to adverse side effects.”

Yastremska has won three WTA titles in her career with a best Grand Slam performance a run to the fourth round at Wimbledon in 2019.

She was embroiled in scandal six months ago after posting a picture of herself wearing blackface to social media.

– AFP



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Safety probe reveals why alleged drug flight between PNG and Australia ended in disaster


An alleged drug flight to smuggle 500kg of cocaine from Papua New Guinea to Queensland came to a fiery end in July last year after a wing tip was ripped off a plane while landing in torrential rain on makeshift airstrip outside the capital Port Moresby.

Papua New Guinea’s Accident Investigation Commission has released a report that details how the drug run – thought to be the biggest in the country’s history – came undone. 

The report highlighted failures in the management of aviation distress signals and search and rescue operations in PNG.

Australian pilot David John Cutmore told investigators he turned off the plane’s transponder to fly at low altitude into PNG on 26 July.

Wing tip sheered off during landing.

AIC Report

“As the aircraft approached to land, the outboard section of the left wing clipped a tree and separated from the aircraft and the pilot continued on with the approach and landed,” the report said.

The damaged plane was loaded with “cargo”, which police allege was half-a-tonne of cocaine, and refuelled.

After 20 minutes on the ground at Papa-Lealea, Cutmore attempted to take-off.

“The pilot reported … he lined up and commenced the take-off roll. As the aircraft lifted off, he noticed that the airspeed indicator was not working and that the aircraft was not achieving a positive rate of climb,” the report said.

He touched back down and careered off the end of the airstrip. The AIC report said the missing section of left wing affected the plane’s ability to produce lift.

Alleged haul of cocaine.

Alleged haul of cocaine.

AFP

AFP officers waiting at Mareeba airport to nab the pilot and the estimated $160m haul were left empty handed after a two-year investigation code-named Operation Weathers.

But five people were later charged in Queensland and Victoria over the failed smuggling operation.

Cutmore, an unemployed flight instructor, turned himself in to authorities in PNG and has since pleaded guilty to one charge of unlawful entry in breach of immigration laws. He has not been charged with any other offences.

David John Cutmore arrives at PNG court last year.

David John Cutmore arrives at PNG court last year.

EMTV

AIC reported the force of the impact automatically set-off the plane’s emergency beacon but PNG authorities accounted for all local aircraft and ignored the distress signal.

Investigators said they could not be sure if the “cargo” contributed to the crash because it had been unloaded and the plane set on fire afterwards by the smugglers.

By the time AIC investigators finally arrived, PNG police and AFP officers had already secured the crash site.

The report into the safety issues recommended government-owned NiuSky Pacific (formerly PNG Air Services) “implement effective procedures” to manage distress signals and search and rescue operations to international standards.

It noted NiuSky responded saying “operational procedures are in the process of a full review and rewrite” as part of an upgrade of air traffic control systems and manuals “contain adequate procedures” and senior staff are trained for such incidents.

AIC described the NiuSky response as “unsatisfactory” for failing to “address the safety issues identified during the investigation”.

It also recommended PNG’s Civil Aviation Safety Authority (CASA) ensure effective oversight of aviation service providers’ search and rescue operations.

A spokesperson for Australia’s CASA said, “it will review the report and consider any associated safety related issues”.

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Canada to delay drug price reforms by six months, industry group says


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TORONTO — Canada has delayed the implementation of new drug price rules that had been due to go into effect on Friday by six months, the pharmaceutical industry’s main lobby group said on Wednesday.

The pharmaceutical industry has fought the new regime, meant to reduce patented drug prices that are among the highest in the world, for years.

“The middle of a global pandemic is not the time to implement measures that will distract from the fight against COVID-19,” said Innovative Medicines Canada (IMC), which represents major drugmakers in Canada.

“This delay provides the time and the opportunity for government to work closely with industry, patients and other health system stakeholders on a better path forward.”

The rules are now set to go into effect on July 1, 2021, according to IMC. Health Canada did not immediately comment.

Reuters reported in November that industry had made a last-ditch C$1 billion ($784 million) proposal to the federal government in hopes of fending off parts of the crackdown. The government said its position had not changed.

The regulations change which countries Canada’s Patented Medicine Prices Review Board (PMPRB) uses as a benchmark to set some maximum drug prices. The PMPRB will drop the United States and Switzerland from its comparisons, and add nations with lower prices.

They will also empower the PMPRB to consider the cost-effectiveness of new drugs, and their potential impact on government budgets, a new approach for the federal watchdog.

($1 = 1.2762 Canadian dollars) (Reporting by Allison Martell Editing by Nick Zieminski)



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Panthers’ Naden gets one-month drug ban


Penrith star Brent Naden is free to return to training on January 1 after he escaped with a one-month ban for cocaine use following the NRL grand final.

The sanction was announced on Tuesday at the end of anti-doping processes held by Sport Integrity Australia and the NRL, and is backdated to the start of his provisional suspension on December 1.

The NRL released a statement saying the penalty is in line with new provisions of the incoming World Anti-Doping Code 2021, which has slashed penalties for cocaine use provided the athlete can establish it was used out of competition and was unrelated to sport performance.

“Having established that the ingestion of the cocaine was out-of-competition and not for performance enhancing purposes, Naden is sanctioned in accordance with new provisions of the incoming World Anti-Doping Code 2021 which permit a one-month period of ineligibility for qualifying athletes who also undertake an approved rehabilitation program,” the NRL said.

“The sanction will come into effect on 1 January 2021 with the commencement of the new WADA Code.”

The NRL said the penalty only related to the anti-doping breach and the 24-year-old outside back could face further sanctions, with the matter to be reviewed in the new year.

Naden entered a rehabilitation facility in Sydney to deal with drug and alcohol issues after fronting Panthers staff in the days following the grand final loss to Melbourne, admitting recreational drug use.

The Panthers said they continued to support Naden, who was “working through his personal issues”.

“Our club acknowledges the penalty handed to Brent Naden by the NRL in relation to his use of a recreational drug,” said Panthers boss Brian Fletcher.

“Brent has come to understand the significant impact of his actions on his family, our club and the game of rugby league.

“He similarly understands how fortunate he is to have the opportunity to return to the NRL in 2021.”

The club said Naden would be back at pre-season training next week.





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