Scientists at EPFL and ETHZ have developed a new method for building microrobots that could be used in the body to deliver drugs and perform other medical operations.
For the past few years, scientists around the world have been studying ways to use miniature robots to better treat a variety of diseases. The robots are designed to enter the human body, where they can deliver drugs at specific locations or perform precise operations like clearing clogged-up arteries. By replacing invasive, often complicated surgery, they could optimize medicine.
EPFL scientist Selman Sakar teamed up with Hen-Wei Huang and Bradley Nelson at ETHZ to develop a simple and versatile method for building such bio-inspired robots and equipping them with advanced features. They also created a platform for testing several robot designs and studying different modes of locomotion. Their work produced complex reconfigurable microrobots that can be manufactured with high throughput. They built an integrated manipulation platform that can remotely control the robots’ mobility with electromagnetic fields, and cause them to shape-shift using heat.
Unlike conventional robots, these microrobots are soft, flexible, and motor-less. They are made of a biocompatible hydrogel and magnetic nanoparticles. These nanoparticles have two functions. They give the microrobots their shape during the manufacturing process, and make them move and swim when an electromagnetic field is applied.
Building one of these microrobots involves several steps. First, the nanoparticles are placed inside layers of a biocompatible hydrogel. Then an electromagnetic field is applied to orientate the nanoparticles at different parts of the robot, followed by a polymerization step to ‘solidify’ the hydrogel. After this, the robot is placed in water where it folds in specific ways depending on the orientation of the nanoparticles inside the gel, to form the final overall 3D architecture of the microrobot.
Once the final shape is achieved, an electromagnetic field is used to make the robot swim. Then, when heated, the robot changes shape and ‘unfolds’. This fabrication approach allowed the researchers to build microrobots that mimic the bacterium that causes African trypanosomiasis, otherwise known as sleeping sickness. This particular bacterium uses a flagellum for propulsion, but hides it away once inside a person’s bloodstream as a survival mechanism.
The researchers tested different microrobot designs to come up with one that imitates this behaviour. The prototype robot presented in this work has a bacterium-like flagellum that enables it to swim. When heated with a laser, the flagellum wraps around the robot’s body and is ‘hidden’.
‘We show that both a bacterium’s body and its flagellum play an important role in its movement,’ said Sakar. ‘Our new production method lets us test an array of shapes and combinations to obtain the best motion capability for a given task. Our research also provides valuable insight into how bacteria move inside the human body and adapt to changes in their microenvironment.’
For now, the microrobots are still in development. ‘There are many factors we have to take into account,’ says Sakar. ‘For instance, we have to make sure that the microrobots won’t cause any side-effects in patients.’

EPFL http://tinyurl.com/zg3rssf

Researchers working in four labs at UT Southwestern Medical Center have found a chink in a so-called ‘un-druggable’ lung cancer’s armour – and located an existing drug that might provide a treatment.

The study describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumours in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for treatment of other types of cancer, primarily leukaemia and lymphoma but also gynaecological, brain, prostate, and head and neck cancers.

Lung cancer is the No. 1 cancer killer in the U.S., responsible for more than 158,000 deaths a year, according to the National Cancer Institute (NCI), and the KRAS oncogene is believed to be responsible for about 25 percent of all lung cancer cases. The 5-year survival rate for lung cancer is below 18 percent.

Cancers caused by the KRAS mutation have been a target for researchers since the mutation was discovered in humans in 1982. But, due in part to this oncogene’s almost impervious spherical shape, no one was able to find an opening for attack, said Dr. Pier Scaglioni, Associate Professor of Internal Medicine at UT Southwestern and a contributing author to the study.

Dr. Michael A. White, Adjunct Professor of Cell Biology and senior author of the study, assembled multiple research teams and used robotic machines to create and sift through trays with thousands of cancer cell/potential drug combinations to uncover the KRAS mutation’s weakness.

The scientists found that targeting and inactivating the protein XPO1, found in the cell nucleus and used to transport gene products from the nucleus to the cytoplasm, killed most of the KRAS mutant cancer cells.

‘We found that inhibiting the XPO1 gene kills lung cancer cells that are dependent on KRAS,’ Dr. Scaglioni said. ‘The unexpected coincidence here is that there is an existing drug that will inhibit XPO1.’

‘We know that this drug hits the XPO1 target in people,’ added Dr. White, also a research executive at Pfizer Inc. ‘But we will not know whether the drug will be effective until clinical trials are done, which should be completed in about two years.’

Based on the results of this study, Selinexor, developed by Karyopharm Therapeutics, will be the focus of a multi-centre lung cancer clinical trial led by UT Southwestern’s Dr. David Gerber, Associate Professor of Internal Medicine. That trial is expected to open for enrolment next year.

UT Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2016/september/kras-cancer-white.html

Simultaneous injections of the radiopharmaceuticals fluorine-18 fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) followed by quantitative scanning significantly improves image quality and detection of bone metastases at a lower dose, according to research presented at the 2017 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI).
“For certain patients with breast and prostate cancer who require evaluation of metastatic disease, a single PET/MR exam can provide more accurate information with less radiation dose in one procedure that is more convenient for patients and potentially less costly for the healthcare system,” said Andrei Iagaru, MD, associate professor of radiology and division chief, Nuclear Medicine and Molecular Imaging, Stanford University School of Medicine in Stanford, Calif.  
Dual-agent PET/MR is further supported by time of flight, a quantitative feature of modern PET image reconstruction that approximates the position where photons are created as radioactive agents decay, which translates into finer image quality.
For this study, researchers prospectively enrolled 55 cancer patients—39 men with prostate cancer and 17 women with breast cancer, ages 34 to 85, in line for conventional bone scan to determine the spread of their disease. All participants were administered simultaneous injections of the imaging agent 18F NaF for the evaluation of bone turnover and FDG for increased metabolic activity and/or inflammation.
After injection, scientists performed PET/ MRI scans with time of flight capability and compared the results with conventional technetium 99m-methyl diphosphonate (99mTc MDP) bone scintigraphy. Results of the study showed improved detection of prostate and breast cancer that had metastasized to bone. Dual-agent PET/MR pointed to bone metastases in 22 patients who were also found positive for metastases with conventional bone scan. In addition, PET/MR detected more bone metastases in 14 patients when compared to the conventional bone scan, which caught only one lesion that was not detected by PET/MR.
Researchers concluded that PET/MR found a greater extent of metastases and, as an added benefit, significantly reduced the required radiation dose from the injected agents—80 percent less from 18F-NaF and 67 percent less from 18F-FDG.

Society of Nuclear Medicine and Molecular Imaging www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=24410

In the last decade, mounting evidence has linked seizure-like activity in the brain to some of the cognitive decline seen in patients with Alzheimer’s disease. Patients with Alzheimer’s disease have an increased risk of epilepsy and nearly half may experience subclinical epileptic activity – disrupted electrical activity in the brain that doesn’t result in a seizure but which can be measured by electroencephalogram (EEG) or other brain scan technology.
In a recent feasibility study, clinician-scientists at Beth Israel Deaconess Medical Center (BIDMC) tested an anti-epileptic drug for its potential impact on the brain activity of patients with mild Alzheimer’s disease. The team, led by Daniel Z. Press, MD, of the Berenson-Allen Center for Non-invasive Brain Stimulation at BIDMC, documented changes in patients’ EEGs that suggest the drug could have a beneficial effect.
“In the field of Alzheimer’s disease research, there has been a major search for drugs to slow its progression,” said Press, an Instructor of Neurology in the Cognitive Neurology Unit at BIDMC and an Associate Professor of Neurology at Harvard Medical School. “If this abnormal electrical activity is leading to more damage, then suppressing it could potentially slow the progression of the disease.”
In this double-blind within-subject study, a small group of patients with mild Alzheimer’s disease visited BIDMC three times. At each visit, patients were given a baseline (EEG) to measure the electrical activity in the brain. Next, patients were given injections containing either inactive placebo or the anti-seizure drug levetiracetam, at either a low dose (2.5 mg/kg) or a higher dose (7.5 mg/kg). Neither patients nor medical professionals knew which injections patients were receiving, but each patient eventually got one of each type, in a random order.
After receiving the injection, patients underwent another EEG, then magnetic resonance imaging (MRI) – which measures blood flow in the brain, another way to quantify brain activity and determine where in the brain it is taking place. Finally, patients took a standardized cognitive test, designed to measure memory, executive functioning, naming, visuospatial ability and semantic function – capabilities all affected by Alzheimer’s disease.
In the seven patients able to complete the study protocol successfully, Press and colleagues analysed changes in their EEGs. (Blood flow analysis from the MRI data is still underway.) Overall, higher doses of the anti-seizure drug appeared to normalize abnormalities seen in the patients’ EEG profiles. That is, researchers saw overall increases in brain wave frequencies that had been abnormally low in Alzheimer’s disease patients prior to receiving the higher dose of levetiracetam, and, likewise, saw decreases in those that had been abnormally high.
“It’s worth noting, we did not demonstrate any improvement in cognitive function after a single dose of medication in this study,” said Press. “It’s too early to use the drug widely, but we’re preparing for a larger, longer study.”

Beth Israel Deaconess Medical Center
www.bidmc.org/News/PRLandingPage/2017/June/Press-Anti-Epilepsy-Alzheimers.aspx

Patients with hypertrophic cardiomyopathy are urged to take it easy. But new research shows they might benefit from moderate aerobic exercise.
Exercise for cardiovascular disease patients.
As one of the most common causes of sudden cardiac death in young people, hypertrophic cardiomyopathy can push patients into sedentary lifestyles.

Current guidelines recommend people with HCM, the most common genetic cardiovascular disease, limit intense exercise because of concerns over triggering ventricular arrhythmias. But new Michigan Medicine research finds there may be reason to re-evaluate the guidelines.

‘We are challenging the idea that exercise is dangerous for these patients,’ says senior author Sharlene Day, M.D., a Michigan Medicine cardiologist and associate professor. ‘And we show that it can actually be beneficial.’

University of Michigan researchers collaborated with colleagues at Stanford University and the VA Palo Alto Health Care System for the study, released in JAMA and presented as a late-breaking clinical trial at the American College of Cardiology’s annual Scientific Session.

The preliminary study announced a small but statistically significant increase in exercise capacity in HCM patients who underwent moderate-intensity exercise training.

The general population is encouraged to stay active to maintain good health and reduce the risk of cardiovascular events. Yet because of the risk of sudden cardiac death, people with HCM are told not to participate in competitive sports.

But there isn’t a global consensus on whether it’s safe for those with HCM to participate in recreational activities, such as jogging. Surveys have revealed most patients with HCM reduce their activity levels after diagnosis, becoming less active than the general population.

First author Sara Saberi, M.D., says providers need data to guide their recommendations so they don’t become coloured by emotion.

‘We have those images entrenched in our brains of young, healthy athletes collapsing suddenly in the middle of a competition, and these devastating events trigger a visceral response,’ says Saberi, a Michigan Medicine cardiologist and assistant professor. ‘But by limiting exercise, we’re creating another set of health problems that stem from obesity, like coronary heart disease, diabetes, obstructive sleep apnoea, depression and anxiety.’

Saberi’s team studied 136 patients with HCM between ages 18 and 80. For 16 weeks, members of one group were told to continue with their usual level of physical activity while the other group members were given individualized exercise plans the researchers created.

The exercises were moderate, including walking, using an elliptical machine, jogging or biking, and excluding intervals or weight training. The participants began week one working out at least three times each week for 20 minutes. By the end of the program, they were working out four to seven times per week for up to an hour.

The exercise group participants experienced a small but statistically significant increase in peak VO2 max, a measure of exercise capability, after the 16 weeks. Reduced peak VO2 is common in HCM patients, and it correlates with mortality in HCM.

‘The findings show patients that follow an exercise prescription can actually train and improve their functional capacity,’ Saberi says.

In this preliminary study, neither group experienced any major adverse effects, such as death, appropriate shocks from an implantable cardioverter-defibrillator or sustained ventricular tachycardia.

Of note, there was also a statistically significant improvement in self-reported physical functioning in the exercise group compared with the usual-activity group.

‘The findings show patients that follow an exercise prescription can actually train and improve their functional capacity.’

Michigan Medicine labblog.uofmhealth.org/lab-report/moderate-exercise-may-be-beneficial-for-hcm-patients