Stem cell researcher in line to become Australian of the Year 2017

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Alan is acknowledged as having laid the foundation for the next generation of researchers in his field. Photo David Kelly

ALAN Mackay-Sim’s fascination with the human body stretches back to his childhood in Sydney.

“I remember being about 12 and wandering down an uneven bush track and thinking, ‘How the hell can I walk along here and compensate for the ground, the uneven ground, and it’s all automatic?’” He says. “It was a feeling of wonder at how we work and I remember even then thinking I’d one day like to figure it out.”

Today the celebrated biomedical scientist and professor at Queensland’s Griffith University is a world authority on the human sense of smell and his groundbreaking work with stem cells has given hope to thousands of Australians with spinal cord injuries.

As director of the National Centre for Adult Stem Cell Research, Alan championed has the use of stem cells to understand brain disorders and diseases including schizophrenia, Parkinson’s disease and hereditary spastic paraplegia.

Though he is now retired, Prof Alan Mackay-Sim’s goal is to progress clinical trials in a drug that he and his team have found for a disease called hereditary spastic paraplegia.

He also led the world’s first clinical trial using stem cells to treat spinal cord injury.

In 2014 Alan’s research played a key role in the first ever successful restoration of mobility in a paraplegic person. “The patient was a man in Poland who had a stab wound to his spinal cord in the thoracic chest region,” says Alan.

“Since the treatment he’s standing, he’s walking on a walker and this year I’ve seen a video of him walking better and riding a tricycle around a gym. His feet are strapped in but he can deliver power to his legs to ride and to steer and … it’s bloody amazing!”

Ever the scientist, however, Alan cautions that much work lies ahead if progress is to be made in benefiting other people with spinal cord injuries. “While the patient in Poland is a very good achievement, it’s scientifically the conservative to say, ‘Well that’s one example. Give me some more examples,’” says Alan.

“It’s three years since he had the injury and the odds are that this is because he had these cells put in his spinal cord rather than some other effect but, you know, yes — you really need to repeat it to show that it’s pretty impressive.”

Mackay-Sim led the world’s first clinical trial using stem cells to treat spinal cord injury.

Although retired, Alan remains emeritus professor at Griffith University and lists repeating the success that was had in Poland as one of his major goals. “We have a team whose intentions are to move the clinical trials forward,” he says. “I’m chair of a scientific advisory board for that so that’s one goal — to see the next phase of clinical trials.

“My other goal is to progress our clinical trials in a drug that we’ve found for a disease called hereditary spastic paraplegia. We’ve got a drug that we’re going to take to clinics to phase one clinical trials, for safety trials. My goal would be to take that through to phase two, which is the efficacy trial, and to get that drug into the population.”

Today, Alan is acknowledged as having laid the foundation for the next generation of researchers in his field and says the future of medical science is immensely exciting.

“I started my university degree in 1970,” he says. “In that time our understanding of neuroscience has multiplied 1000 times over. And with the technologies that are available, and with our application of all sorts of chemistries; all sorts of computing techniques, all sorts of machinery and instruments, technologies like the genome, the stem-cell technologies — these are all huge developments.”

“It’s an exciting time to be around and if we can afford the science I can definitely say can there’s a rosy future for humanity ahead.”

CommBank have been proud partners of Australian of the Year Awards for over 37 years, celebrating and championing those who make our country a better place. The awards honour an extraordinary group of respected Australians, whose actions inspire conversation on issues of national importance.

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This implantable micro-machine can deliver medications from inside the body

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Scientists have developed a bio-compatible micro-machine capable of being implanted inside the body, where it could act as a wireless medical device to deliver drugs directly under the skin.

The device, which measures only 15 millimetres long, is actually a squishy version of a mechanism called a Geneva drive, which has been used in wristwatches going as far back as the 17th century. Only this time, it would be worn inside and not outside the body.

Most of today’s implanted medical aids are made from static components that don’t allow freely moving parts. And because they often include batteries or other kinds of electronics that are toxic to the body, they can create complications with the human tissue that surrounds them.

Of course, devices such as pacemakers have been successfully implanted in patients for decades, but compared to inflexible, metallic devices, researchers think soft, supple implants could make a range of new medical treatments possible in the future.

“Traditional implantable devices are made of silicon or metal, and there are certain manufacturing processes that you would use to make devices out of those materials,” researcher Samuel Sia from Columbia University told Abby Olena at The Scientist.

“But they don’t work on biological materials, which are much softer, and so we had to develop our own methods.”

To develop an implant with moving parts that could be safely implanted inside the body, the team turned to hydrogels – a material composed of polymer chains with high water content (over 90 percent), which makes it soft, flexible, and highly compatible with biological tissue.

Using a method to stack layered sheets of this hydrogel, the researchers can fabricate their squishy Geneva drive in about 30 minutes – but developing the technique and discovering the right materials to use took some eight years of research.

The team ultimately decided on polyethylene glycol (PEG)–based hydrogels, which are biodegradable and approved by the FDA for use in medical devices.

“Of course, you have other devices that are also made out of bio-compatible materials, but those are mostly passive devices,” researcher Albert van den Berg from the University of Twente in the Netherlands, who was not involved in the study, told The Scientist.

“[T]hese are active, command-able devices. It’s really a breakthrough.”

Each full revolution of the small gear rotates a larger gear by 60 degrees, exposing one of six potential drug reservoirs to an aperture, through which medication can be released to the body.

While the device isn’t a fully independent micro-robot, capable of acting on its own, it is a machine that can perform its function inside the body without any direct physical contact with the outside world – save the nearby presence of a single magnet.

In testing with mice bred to develop bone cancer (osteosarcoma), the researchers magnetically triggered the release of the chemotherapy medication doxorubicin over the course of 10 days.

The results showed that using the device with just 10 percent of a regular doxorubicin dosage was more effective in stopping tumour growth and killing cancer cells than conventional chemotherapy – with a 56 percent reduction in cancer cells for iMEMS, compared with 39 and 19 percent reductions for high- and low-dosage systemic treatments respectively.

The device was also less toxic to the subject overall than a conventional treatment, since such a reduced amount of chemotherapy medication was released.

While it’s early days for the technology as a whole, and these promising results have only been seen in mice so far, the researchers hope that one day their micro-machines could be used to deliver cancer-fighting medications in humans – or other kinds of drugs we need, like insulin.

“People are already making replacement tissues and now we can make small implantable devices, sensors, or robots that we can talk to wirelessly,” Sia said in a press release.

“Our iMEMS system could bring the field a step closer to developing soft miniaturised robots that can safely interact with humans and other living systems.”

The findings are reported in Science Robotics.

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Scientists are genetically engineering Salmonella to destroy brain tumours

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Salmonella is commonly linked to fevers and food poisoning, and generally speaking, it isn’t good news at all for your body. But scientists have come up with an exception: a genetically engineered form of Salmonella bacteria that can eat away at cancer tumours.

The modified bacteria target tumours in the brain rather than seeking out the human gut where Salmonella usually causes damage – and the technique could lead to  a highly targeted technique of fighting one of the worst types of cancer there is.

Researchers from Duke University gave the treatment to rats with the aggressive brain cancer glioblastoma, and saw significant increases in lifespans, with 20 percent of the rodents surviving an extra 100 days compared to control animals – the equivalent of 10 years in human terms.

“Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal,” says one of the team, Johnathan Lyon.

“And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging.”

salmonella-close-lookBacteria (pink) take hold of cancer cells (blue). Credit: Duke University

It’s a promising direction of study, since survival rates of humans with this cancer are pretty bleak. Only about 30 percent of patients with glioblastoma live for more than two years after diagnosis.

Part of what makes it so hard to treat is that the tumours hide behind the blood-brain barrier, which separates the circulating blood from the brain’s own fluid.

Conventional drugs can’t easily reach through this membrane, so a more targeted approach is needed to stop glioblastoma from thriving.

To achieve this, the researchers used a genetically adjusted and detoxified form of Salmonella typhimurium, modified to be deficient in a crucial organic compound called purine.

Glioblastoma tumours are an abundant source of this enzyme, which induces the bacteria to seek out the cancer cells to get the purine that they need.

And when the bacteria get to the tumours, two more genetic tweaks kick into action.

Because cancerous cells multiply so quickly, oxygen is scarce inside and around tumours. Knowing this, the scientists coded their Salmonella to produce two proteins called Azurin and p53 in the presence of low levels of oxygen.

These compounds instruct the cancer cells to effectively self-destruct, so the end result is like a genetically-coded guided missile, seeking out the tumour and blitzing cancerous cells when it arrives.

The researchers say the technique is much more accurate than surgery, and because the bacteria are otherwise detoxified, there should be no damaging side effects for the patient.

Of course, having success with a group of rats is no guarantee that the treatment will translate to the human body, but the researchers are hopeful that the technique can be developed to treat cancer patients in the future.

The first step is to get that 20 percent success rate up. Based on initial tests, the 80 percent of cases where the treatment had no effect could be down to the tumour cells outpacing the bacteria, or inconsistencies in the Salmonella‘s penetration in the body.

“It might just be a case of needing to monitor the treatment’s progression and provide more doses at crucial points in the cancer’s development,” says Lyon.

“However, this was our first attempt at designing such a therapy, and there is some nuance to the specific model we used, thus more experiments are needed to know for sure.”

The research has been published in Molecular Therapy Oncolytics.

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Scientists have used bacteria to kill antibiotic-resistant superbugs

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I know you’ve already got a lot to worry about, what with the North Pole being 20 degrees hotter than it’s supposed to be, and the polar bear that went and crushed all our hearts this week, but don’t forget to feel concerned about the looming antibiotic resistance crisis sometimes.

If things keep going as they are, antibiotic-resistant superbugs are expected to kill 10 million people by 2050, and so far, we have no solution. But researchers have found that we could actually fight fire with fire – a predatory bacterium has been shown to kill antibiotic-resistant bugs.

The bacterium in question is called Bdellovibrio bacteriovorus, and it’s known as a predatory bacterium, because it seeks out and consumes its own kind.

A team from Imperial College London and the University of Nottingham in the UK decided to pit it against an antibiotic-resistant strain of the human pathogen Shigella flexneri – a common cause of food poisoning.

Shigella bacteria are responsible for making 160 million people sick each year (diarrhoea is its speciality), and more than 1 million people die each year from infection, mostly because of contaminated food.

There is currently no vaccine to prevent Shigella infection, and in many cases, antibiotics will not help – most patients are told to just wait it out until the infection resolves itself in five to seven days.

It’s a formidable foe – but not for Bdellovibrio, it seems.

When the researchers combined the two types of bacteria in the lab, Bdellovibrio caused the population of antibiotic-resistant Shigella to decline 4,000-fold.

Next they infected live zebrafish larvae with Shigella, and gave them a shot of Bdellovibrio. Rates of survival for the larvae were around 60 percent.

For the control group that didn’t get a shot of Bdellovibrio, only 25 percent of them lived long enough to reach the third day of infection.

The bacteria are so effective because they eat the Shigella bacteria from the inside out, growing large and swollen before bursting out of their dead host’s shell.

So far, the researchers have found no evidence of unwanted side effects from infecting the larvae with Bdellovibrio, and the same could be true for us, James Gallagher reports for the BBC, because previous research has found Bdellovibrio bacteria occurring naturally in healthy humans.

“This study really shows what a unique and interesting bacterium Bdellovibrio is, as it presents this amazing natural synergy with the immune system and persists just long enough to kill prey bacteria before being naturally cleared,” says one of the team, Serge Mostowy from Imperial College London.

While the introduced population of Bdellovibrio appeared to give the zebrafish larvae some level of protection even if they’d had their immune system compromised as part of the experiment, the researchers say the strongest response seems to come from the predatory bacteria working in tandem with the host’s own white blood cells.

“The predatory action of the Bdellovibrio breaks the Shigella-pathogen cells, and this stimulates the white blood cells; redoubling their ‘efforts’ against the pathogen and leading to increased survival of the zebrafish ‘patients’,” says one of the researchers, Liz Sockett from the University of Nottingham.

Of course, zebrafish aren’t humans, and humans aren’t zebrafish, so until similar results are demonstrated in humans, we can’t get too excited. But the researchers say this is a promising sign that the answer to the antibiotic resistance crisis could be the very thing we’re trying to fight.

“It may be unusual to use a bacterium to get rid of another, but in the light of the looming threat from drug resistant infections the potential of beneficial bacteria-animal interactions should not be overlooked,” Michael Chew from the Wellcome Trust in the UK, who wasn’t involved in the research, said in a press statement.

“We are increasingly relying on last line antibiotics, and this innovative study demonstrates how predatory bacteria could be an important additional tool to drugs in the fight against resistance.”

The research has been published in Cell Biology.

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USFDA reviews Pfizer’s drug for Metastatic Breast Cancer

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Image result for metastatic breast cancer

Pfizer has announced that the FDA accepted for review a supplemental New Drug Application (sNDA) for its first-in-class CDK 4/6 inhibitor, IBRANCE (palbociclib). The sNDA supports the conversion of the accelerated approval of IBRANCE in combination with letrozole to regular approval and includes data from the phase III PALOMA-2 trial, which evaluated IBRANCE as initial therapy in combination with letrozole for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer. This is the same patient population as the randomized phase II PALOMA-1 trial upon which the accelerated approval of IBRANCE plus letrozole was granted in February 2015.

The sNDA was granted Priority Review status, which accelerates FDA review time from 10 months to a goal of six months from the day of acceptance of filing.1 The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in April 2017.

“Since its introduction in 2015, more than 45,000 patients have been prescribed IBRANCE by more than 9,000 providers in the U.S.,” said Liz Barrett, global president and general manager, Pfizer Oncology. “We are pleased that the PALOMA-2 trial has further demonstrated the significant clinical benefit of IBRANCE in the first-line setting, providing additional evidence for its continued use as a standard of care medicine.”

PALOMA-2 is a randomized (2:1), multicenter, double-blind phase III study that evaluated a total of 666 women from 186 global sites in 17 countries. The study demonstrated that IBRANCE in combination with letrozole improved progression-free survival compared to letrozole plus placebo as a first-line treatment for postmenopausal women with ER+, HER2- metastatic breast cancer. The adverse events observed with IBRANCE in combination with letrozole in PALOMA-2 were generally consistent with their respective known adverse event profiles

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