Archive for month: August, 2020

A drug that blocks neurotransmitters could reduce nausea and vomiting caused by chemotherapy, research co-authored by a Sanford Health physician and published in the New England Journal of Medicine finds.
Sanford oncologist and cancer researcher Steven Powell, M.D., was among a team of researchers who discovered that the drug olanzapine, which is FDA approved for use as an antipsychotic agent, significantly improved nausea prevention in patients who were receiving chemotherapy for cancer treatment. The drug blocks neurotransmitters involved with nausea and vomiting.

‘We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,’ said Powell. ‘The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.’
Researchers noted that within the first day after treatment, 74 percent of study participants experienced no nausea or vomiting when their chemotherapy was paired with olanzapine. When a placebo was used instead of olanzapine, that figure dropped to 45 percent. This benefit continued for five days after chemotherapy treatment for many patients.

Sanford Health www.sanfordresearch.org/newsevents/news/NewsDetail25278.cfm?Id=0,1887

A multicenter team of researchers led by Barbara Murphy, MD, of the Icahn School of Medicine at Mount Sinai has identified a panel of genes which can help predict whether a transplanted kidney will later develop fibrosis, an injury which can cause the organ to fail.

Researchers in the Genomics of Chronic Allograft Rejection (GoCAR) study obtained biopsy samples from transplanted kidneys three months and twelve months after transplantation. Using microarray, a method by which the expression levels of a large numbers of genes or proteins can be measured simultaneously, the researchers determined which genes were correlated with biopsy samples which had an increased Chronic Allograft Damage Index (CADI) score at the 12-month biopsy. The CADI score is a measure of the level of fibrosis in the transplanted kidney. The researchers then narrowed the genes down to a predictive gene set that identified patients at risk for decline in renal function and loss of the transplanted kidney beyond one year. The rate of correlation of the identified gene set with damage was greater than the clinico-pathological variables currently used in practice to identify kidney transplant recipients at risk of allograft damage and loss.

‘This is the first finding of its kind,’ said Barbara Murphy, System Chair of Medicine for the Mount Sinai Health System and Murray M. Rosenberg Professor of Medicine (Nephrology) at the Icahn School of Medicine at Mount Sinai, and the lead investigator on the study. ‘By helping us better understand the causes of damage to transplanted kidneys, this study has the potential to change how we monitor and manage all renal transplant patients.’

‘The study offers the potential to identify renal transplant recipients at risk for a loss of the new organ prior to the development of irreversible damage,’ said Dr. Murphy. ‘This would mean that doctors might eventually have the opportunity to change the therapeutic treatment approach in order to prevent fibrosis from progressing at all.’

Mount Sinai Health System www.mountsinai.org/about-us/newsroom/press-releases/mount-sinai-researchers-identify-way-to-predict-and-prevent-damage-in-donated-kidneys

For medics on the battlefield and doctors in remote or developing parts of the world, getting rapid access to the drugs needed to treat patients can be challenging. Biopharmaceutical drugs, which are used in a wide range of therapies including vaccines and treatments for diabetes and cancer, are typically produced in large, centralized fermentation plants. This means they must be transported to the treatment site, which can be expensive, time-consuming, and challenging to execute in areas with poor supply chains.
Now a portable production system, designed to manufacture a range of biopharmaceuticals on demand, has been developed by researchers at MIT, with funding from the Defense Advanced Research Projects Agency (DARPA).
In a paper the researchers demonstrate that the system can be used to produce a single dose of treatment from a compact device containing a small droplet of cells in a liquid.

In this way, the system could ultimately be carried onto the battlefield and used to produce treatments at the point of care. It could also be used to manufacture a vaccine to prevent a disease outbreak in a remote village, according to senior author Tim Lu, an associate professor of biological engineering and electrical engineering and computer science, and head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics.
‘Imagine you were on Mars or in a remote desert, without access to a full formulary, you could program the yeast to produce drugs on demand locally,’ Lu says.

The system is based on a programmable strain of yeast, Pichia pastoris, which can be induced to express one of two therapeutic proteins when exposed to a particular chemical trigger. The researchers chose P. pastoris because it can grow to very high densities on simple and inexpensive carbon sources, and is able to express large amounts of protein.

‘We altered the yeast so it could be more easily genetically modified, and could include more than one therapeutic in its repertoire,’ Lu says.
When the researchers exposed the modified yeast to estrogen β-estradiol, the cells expressed recombinant human growth hormone (rHGH). In contrast, when they exposed the cells to methanol, the yeast expressed the protein interferon.
The cells are held within a millimeter-scale table-top microbioreactor, containing a microfluidic chip, which was originally developed by Rajeev Ram, a professor of electrical engineering at MIT, and his team, and then commercialized by Kevin Lee – an MIT graduate and co-author – through a spin-off company.
A liquid containing the desired chemical trigger is first fed into the reactor, to mix with the cells.

Inside the reactor, the cell-and-chemical mixture is surrounded on three sides by polycarbonate; on the fourth side is a flexible and gas-permeable silicone rubber membrane. By pressurizing the gas above this membrane, the researchers are able to gently massage the liquid droplet to ensure its contents are fully mixed together.
‘This makes sure that the one milliliter (of liquid) is homogenous, and that is important because diffusion at these small scales, where there is no turbulence, takes a surprisingly long time,’ says Ram, who was also a senior author of the paper.
Because the membrane is gas permeable, it allows oxygen to flow through to the cells, while any carbon dioxide they produce can be easily extracted.
The device continuously monitors conditions within the microfluidic chip, including oxygen levels, temperature, and pH, to ensure the optimum environment for cell growth. It also monitors cell density.
If the yeast is required to produce a different protein, the liquid is simply flushed through a filter, leaving the cells behind. Fresh liquid containing a new chemical trigger can then be added, to stimulate production of the next protein.
Although other research teams have previously attempted to build microbioreactors, these have not have not had the ability to retain the protein-producing cells while flushing out the liquid they are mixed with, Ram says. ‘You want to keep the cells because they are your factory,’ he says. ‘But you also want to rapidly change their chemical environment, in order to change the trigger for protein production.’

The researchers are now investigating the use of the system in combinatorial treatments, in which multiple therapeutics, such as antibodies, are used together.
Combining multiple therapeutics in this way can be expensive if each requires its own production line, Lu says.
‘But if you could engineer a single strain, or maybe even a consortia of strains that grow together, to manufacture combinations of biologics or antibodies, that could be a very powerful way of producing these drugs at a reasonable cost,’ he says.

MIT news.mit.edu/2016/portable-device-produces-biopharmaceuticals-on-demand-0729

Adelaide researchers have made a world-first breakthrough in the early detection of patients’ resistance to a common treatment for chronic myeloid leukaemia, offering some hope that the patients’ treatment could be changed sooner to improve their chances of survival.

The researchers – based in the Cancer Theme at the South Australian Health & Medical Research Institute (SAHMRI) and the University of Adelaide’s School of Medicine – have developed a new test that they believe could be adopted by doctors worldwide.

Lead author and postdoctoral researcher Dr Laura Eadie says one-in-five chronic myeloid leukaemia (CML) patients are resistant to the leading treatment of their condition.

‘The development of the targeted drug Glivec for chronic myeloid leukaemia has been one of the most remarkable success stories in cancer treatment over the past two decades. This is because the drug targets the mutant protein that causes their leukaemia,’ Dr Eadie says.

‘However, about 20% of patients have a poor response to Glivec, and until now we haven’t fully understood why. Unfortunately, this means that one-in-five patients could be receiving treatment that ultimately is not benefitting them, losing response to therapy and reducing their chances of survival.’

The study looked at the role of P-glycoprotein, a protein that pumps many drugs – including Glivec – out of leukaemia cells.

‘Some patients were found to have higher levels of P-glycoprotein in their leukaemic cells after just a few weeks of starting therapy. These patients were much more likely to develop resistance to Glivec later on,’ Dr Eadie says.

‘We’ve found the greater the increase in P-glycoprotein in patients, the greater their risk is of becoming resistant and not responding to their drug any more, or even succumbing to their disease.’

The research team’s work shows, for the first time, that assessing a patient’s levels of the P-glycoprotein soon after they start receiving Glivec therapy will help to predict that patient’s long-term response to the drug.

‘This new test, developed in our laboratory, may provide an opportunity for doctors around the world to change treatment strategies for those patients most at risk of doing poorly on Glivec before they actually lose response to the therapy,’ Dr Eadie says.

University of Adelaide www.adelaide.edu.au/news/news86562.html

It’s a Catch-22 with potentially deadly consequences: People trying to overcome addiction can’t get treatment for their pain, because the most powerful pain medicines also carry an addiction risk.
And so their pain continues to get in the way of their addiction recovery – or they seek pain relief in the same addictive substances they’re trying to avoid.

But a new study shows the potential for patients to break out of that cycle through a non-drug approach that combines behavioural therapy and social support to help them manage their pain. The low-cost approach, grounded in psychological theories of pain, could help address the nation’s epidemic of addictions to opioid painkillers and illicit drugs.

Veterans who received this pain-focused care while also being treated for addiction found that the intensity of their pain decreased, their ability to function increased, and their alcohol use went down, compared to veterans who received a less-focused approach. However, the two groups had similar rates of drug use.

Just 10 weekly sessions of the approach, called ImPAT for Improving Pain during Addiction Treatment, had an effect that lasted up to a year in 55 veterans who took part, according to the new results published by a team from the VA Ann Arbor Healthcare System’s Center for Clinical Management Research and University of Michigan Medical School’s Addiction Center.

The researchers have already launched a follow-up study in a larger group of 480 non-veterans in a residential addiction treatment program. And the study’s authors note that the ImPAT approach has the potential to be easily and inexpensively adopted by addiction treatment centers and groups worldwide, through team members trained in standard psychological techniques.

Addiction treatment programs often have patients who suffer from chronic pain, but offer few options to treat them, Ilgen says.’These results highlight the need for addiction treatment programs to offer a multifaceted approach that doesn’t only address substance use but also the other factors that might be driving substance use, including pain,’ says Mark Ilgen, Ph.D., the study’s lead author and a VA and U-M psychologist specializing in addiction research. ‘We’ve shown that it’s possible to improve pain outcomes in people with addiction, and even have some spillover effects on their substance use.’

To make matters worse, ‘Past studies of psychosocial approaches for pain have often excluded people with drug or alcohol problems, addiction treatment programs do not usually have providers trained in pain care, and many pain specialists will not treat people who also have addiction. So patients are caught in the middle.’

All 129 patients in the study, most of them men in their 40s and 50s, were receiving outpatient addiction treatment in a CBT-based, non-abstinence setting at the Ann Arbor VA. Half were randomly assigned to ImPAT sessions, the other half to support groups of peers, led by a therapist, where pain and addiction could be discussed.

ImPAT combines elements of cognitive behavioural therapy with another psychosocial approach called acceptance and commitment therapy.

While the two approaches aren’t usually used together, they are often used in pain treatment settings – but those clinics and programs don’t often accept people who also acknowledge they have addiction issues. Ilgen and his colleagues hope their results will help bring the techniques into addiction treatment settings, where the cognitive behavioural therapy approach is often used.

The ImPAT technique seeks to use integrated approaches both to help patients focus less on their pain and more on other aspects of life. This includes techniques to help people adapt to their pain, find ways to distract themselves from their pain, and think of ways to function in the face of pain.

‘We want to take the focus off pain and put it onto functioning, and finding pleasurable ways to spend time,’ Ilgen says. ‘There’s also a strong link between depression and pain. Pain is responsive to mood, and mood is responsive to social support.’

University of Michigan www.uofmhealth.org/news/archive/201607/treating-pain-without-feeding-addiction-study-shows-promise