Clinical Research

USFDA approves CLOT Retrieval Devices to help with STROKE

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The U.S. Food and Drug Administration today allowed marketing of two Trevo clot retrieval devices as an initial therapy for strokes due to blood clots (ischemic) to reduce paralysis, speech difficulties and other stroke disabilities. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug (tissue plasminogen activator or t-PA), which needs to be given within three hours of symptom onset.

“This is the first time FDA has allowed the use of these devices alongside t-PA, which has the potential to help further reduce the devastating disabilities associated with strokes compared to the use of t-PA alone,” said Carlos Peña, Ph.D., director of the division of neurological and physical medicine devices at the FDA’s Center for Devices and Radiological Health. “Now health care providers and their patients have another tool for treating stroke and potentially preventing long-term disability.”

The Trevo device was first cleared by the FDA in 2012 to remove a blood clot and restore blood flow in stroke patients who could not receive t-PA or for those patients who did not respond to t-PA therapy. Today’s action expands the devices’ indication to a broader group of patients.

Trevo is a clot removal device that is inserted through a catheter up into the blood vessel to the site of the blood clot. When the shaped section at the end of the device is fully expanded (up to three to six millimeters in diameter), it grips the clot, allowing the physician to retrieve the clot by pulling it back through the blood vessel along with the device for removal through a catheter or sheath.

Stroke kills nearly 130,000 Americans each year and is the fifth leading cause of death, according to the Centers for Disease Control and Prevention. About 87 percent of all strokes are ischemic strokes. Until now, the only first-line treatment for acute ischemic stroke was t-PA administered intravenously.

The FDA evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device along with t-PA and medical management of blood pressure and disability symptoms with 249 patients who had only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent (ranging from no symptoms to slight disability) three months after their stroke, compared to 19 percent of patients who were not treated with the Trevo device.

Risks associated with using the Trevo device include a failure to retrieve the blood clot, device malfunctions including breakage and navigation difficulties, which can potentially damage blood vessels and cause perforation or hemorrhage.

The FDA reviewed the data for Trevo for stroke treatment through the de novo premarket review pathway, a regulatory pathway for devices of a new type with low-to-moderate-risk that are not substantially equivalent to an already legally-marketed device and for which special controls can be developed, in addition to general controls, to provide a reasonable assurance of safety and effectiveness of the devices.

Trevo is manufactured by Concentric Medical Inc. in Mountain View, California.

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USFDA approves Adlyxin to treat type 2 diabetes

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The U.S. Food and Drug Administration approved Adlyxin (lixisenatide), a once-daily injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.

“The FDA continues to support the development of new drug therapies for diabetes management,” said Mary Thanh Hai Parks, M.D., deputy director, Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “Adlyxin will add to the available treatment options to control blood sugar levels for those with type 2.”

Type 2 diabetes affects more than 29 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness and nerve and kidney damage.

Adlyxin is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug’s safety and effectiveness were evaluated in 10 clinical trials that enrolled 5,400 patients with type 2 diabetes. In these trials, Adlyxin was evaluated both as a standalone therapy and in combination with other FDA-approved diabetic medications, including metformin, sulfonylureas, pioglitazone and basal insulin. Use of Adlyxin improved hemoglobin A1c levels (a measure of blood sugar levels) in these trials.

In addition, more than 6,000 patients with type 2 diabetes at risk for atherosclerotic cardiovascular disease were treated with either Adlyxin or a placebo in a cardiovascular outcomes trial. Use of Adlyxin did not increase the risk of cardiovascular adverse events in these patients.

Adlyxin should not be used to treat people with type 1 diabetes or patients with increased ketones in their blood or urine (diabetic ketoacidosis).

The most common side effects associated with Adlyxin are nausea, vomiting, headache, diarrhea and dizziness. Hypoglycemia in patients treated with both Adlyxin and other antidiabetic drugs such as sulfonylurea and/or basal insulin is another common side effect. In addition, severe hypersensitivity reactions, including anaphylaxis, were reported in clinical trials of Adlyxin.

The FDA is requiring the following post-marketing studies for Adlyxin:

  • Clinical studies to evaluate dosing, efficacy and safety in pediatric patients.
  • A study evaluating the immunogenicity of lixisenatide.

Adlyxin is manufactured by Sanofi-Aventis U.S. LLC, of Bridgewater, New Jersey.

 

Study shows cancer cells can ‘hide’ in fatty tissue

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Cancer stem cells can take cover and evade chemotherapy by hiding in fatty tissue, according to new research.

A team of scientists in the US looked at the behaviour of leukaemia stem cells in mice and found they were building their own hideout in the fat – a bolt-hole that then increased their resistance to chemo treatments.

Not only that, but the cancer cells apparently use the fatty deposits to generate extra energy for themselves. The researchers say this activity could help explain why some cancers prove harder to treat, and are more likely to recur.

The fatty tissue acts as a  kind of “robber’s cave” for the cancer cells, according to the team from the University of Colorado Cancer Centre.

“The basic biology was fascinating: the tumour adapted the local environment to suit itself,” said researcher Craig Jordan.

 

When analysing a mouse model of leukaemia, the researchers noted the fatty (or adipose) tissue had a higher concentration of cancer stem cells to regular cancer cells.

Like healthy stem cells, cancer stem cells are capable of developing into several cell types, and are thought to form new tumours and cause relapses.

robbers-caveCredit: University of Colorado Cancer Centre

These cancer stem cells were also found to be triggering a process called lipolysis, where fatty acids are released from tissue to produce energy: in essence, the cells were creating a new energy source for themselves.

When a chemotherapy treatment was introduced, the cancer stem cells hiding in the fatty tissue and living off its acids were noted to be more resistant than the other cancer stem cells outside the tissue. The same effects were found in samples of human leukaemia.

Three clues prompted the scientists to carry out their research: obesity is already linked to a poorer recovery rate for leukaemia patients; cancer stem cells drive growth and can cause relapses in leukaemia; and they rely heavily on the tumour micro-environment they’re in.

With those factors in mind, the researchers wondered – could cancer stem cells in fatty tissue be causing poorer prognosis in obese patients? From the new findings, it seems the answer could be yes, although this is still just a hypothesis for now.

The researchers intend to follow up their study by testing mouse models of different obesity levels, to see if extra fat provides more space for cancer stem cells to hide away in (or more energy for them to live off).

Obesity increases the risk of several cancer types, although scientists haven’t yet pinned down the reason why.

Although this new study doesn’t solve the problem, it means we’re getting closer, giving us new understanding into why leukaemia in overweight patients is harder to fight and more likely to come back.

The findings are published in Cell Stem Cell.

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China on the verge of re-writing HUMAN DNA!

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Next month, Chinese researchers will edit adult human DNA using the revolutionary CRISPR/Cas-9 tool, commonly known as CRISPR, for the first time anywhere in the world.

The researchers will attempt to cut faulty DNA out of the cells of lung cancer patients who have failed to respond to all other conventional treatments.

Chinese scientists have previously used CRISPR on non-viable human embryos, without much luck, but this is the first time any researchers, anywhere in the world, will use the tool to edit DNA in an adult. 

If successful, the hope is that it could lead to further CRISPR treatments – CRISPR/Cas-9 allows researchers to effectively cut and paste DNA in cells, and, in animals, it’s already been shown to treat genetic diseases such as Duchenne muscular dystrophy.

The new trial will begin at Sichuan University’s West China Hospital next month, according to Nature, and will involve patients who’ve already gone through chemotherapy and radiation therapy – in other words, are out of options.

 In the past, scientists have spoken out about the ethical concerns surrounding the use of CRISPR, which is capable of causing genetic changes to sperm and egg cells that can be passed down to future generations.

There are also concerns that it could lead to the development of ‘designer’ babies – where parents pick and choose certain traits to write into their child’s DNA.

But it’s important to note that the new Chinese study will only edit patients’ immune system T-cells, and not affect gamete cells that could be passed down to offspring.

In other words, the changes made by CRISPR will be limited to the patient involved in the trial – a number that hasn’t been disclosed as yet.

We do know what the process will involve, though.

In the trial, the Chinese scientists will extract T-cells from patients’ blood and delete a gene that produces a protein called PD-1, which stops T-cells from targeting and killing cancer cells, from their DNA.

The team will then multiply these new CRISPR-modified T-cells in the lab, before injecting them back into the patients to flood their immune system.

The hypothesis is that, with PD-1 inhibited, the T-cells will be able to track down and wipe out lung cancer cells naturally.

While CRISPR/Cas-9 is capable of also inserting new DNA into a cell’s genome, in this study, genetic information will only be deleted, not added.

This is a similar process to immunotherapy studies that are already common around the world – researchers take immune cells, genetically modify them, and insert them back into patients. In fact, gene editing has already saved the life of a girl with ‘incurable’ leukaemia.

But what’s different in this case is the use of CRISPR, which is incredibly simple and versatile.

While in the past it’s taken years for scientists to develop the right molecular ‘scissors’ to cut out specific genes, CRISPR simply needs to be programmed and can then work for any part of the genome – no costly development required.

Last month, the US National Institutes of Health (NIH) approved a similar trial in the states – although the American research will also add an extra gene to help combat three types of cancer: melanoma, sarcoma, and myeloma. 

The research could begin as early as this year, but if reports are anything to go off, China will be the first to try out this incredibly powerful tool in humans.

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Researchers trick our cells into treating UTIs without antibiotics

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New research shows that our bodies own immune systems have another way to fight off urinary tract infections (UTIs) without antibiotics – and it’s super effective.

This is a pretty big deal, seeing as UTIs are one of the most common infections treated with antibiotics in humans – something that’s contributing to the rise of drug-resistant superbugs.

Right now, bacteria in the US are readily becoming resistant to our last lines of antibiotics, hospital infections are getting more and more deadly, and even gonorrhoea is on the verge of being untreatable in the near future.

So finding anything that can treat bacterial infections without antibiotics is incredibly exciting for scientists.

UTIs are usually caused by E. coli (Escherichia coli) or other bacteria entering the urinary tract and attaching to the cell wall of the bladder, urethra, or kidneys (with kidney infections being the most severe).

Researchers already know that the bladder has a bunch of defence mechanisms it uses to try and minimise infection. One of these involves the lining of the bladder shedding frequently, so any bacteria that attach get washed out.

 But that doesn’t work in all cases, and if E. coli does manage to attach to the bladder wall, the resulting infection can be painful, and unpleasant – especially if antibiotics aren’t able to clear it. There are currently 8.1 million doctors’ visits annually in the US just as a result of UTIs.

But now Duke University researchers have shown in detail for the first time a pathways through which bladder cells can actually kick out the bacteria that cause UTIs – and are now looking into how they can harness it to treat the infections without antibiotics.

“We found that the process which cells use to secrete chemicals also appears to be the way to clear urinary tract infections,” said Yuxuan Phoenix Miao, one of the researchers, in an interview with ResearchGate.

 “Bacterial pathogens hide within a membranous vesicle in the bladder cells,” said Miao. “We revealed that a protein complex important for secreting hormones called ‘Exocyst’ can precisely recognise and locate bacteria hiding in those vesicles, then promote transport of these bacteria-laden vesicles towards the cell surface, and throw the bacteria out of the bladder cell.”

Even cooler, bladder cells can tag those vesicles with bacteria inside, so the immune system can remove the offending bacteria.

To do that, the immune system usually sends in lysosomes – organelles that eat and break down virtually anything in a cell, including bacteria. But occasionally the bacteria manage to survive this process, and when a lysosome eventually bursts, the freed bacteria go back and re-infect the cell.

But last year the same researchers also discovered that lysosomes can detect if the bacteria they’ve eaten isn’t breaking down, and vomit up the offending bacteria – which means they can be cleared away by other parts of the immune system.

“It was thought that lysosomes always degrade their contents,” Miao said last year. “Here we are showing for the first time that when the contents cannot be degraded, the lysosome appears to have a back-up plan which is to expel the contents in capsules.”

So, in other words, the team has shown in detail how our cells have the ability to clear even the most stubborn of bacteria – which means they can look for ways to tweak the process to make sure it happens more regularly, and on demand.

The researchers are now looking into current medicines and other substances to see if they can trigger this natural clearing mechanism with more accuracy and control. The plant extract Forskolin is currently a possible candidate for testing.

“Previous studies from our lab have found that Forskolin can dramatically enhance the bacteria clearance effect by promoting the bacteria export process,” said Miao. “Now that we have identified the pathway which the bladder cells use to export bacteria, we can start to examine whether Forskolin enhances bacteria expulsion by promoting the function of the Exocyst and if so, how.”

The research was published in Immunity

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