Researchers have found that some of the harmful effects of a commonly used cancer drug can be alleviated by using gene therapy that stimulates blood vessel growth in the heart. Doxorubicin treatment, which is commonly used in a variety of cancers, leads to cardiac atrophy and body wasting. Researchers from the Wihuri Research Institute and the University of Helsinki found that in mouse heart, doxorubicin leads to blood vessel rarefaction, which was prevented by treatment with gene therapy using the VEGF-B growth factor.

As advances in cancer treatment have decreased deaths from cancer, doxorubicin-induced heart problems have become an increasing problem. ‘The new findings give hope that in future the heart could be protected by gene therapy, allowing more thorough cytostatic cancer treatment. Thus, the cancer itself would be treated more effectively and the adverse effects could be avoided’, explains Markus Rasanen, MD, who made the discovery during his thesis studies.

‘Doxorubicin, a cytostatic agent of the anthracycline class, that was used in this study has been a target of intensive research in the scientific world for a long time, and its role has been described in thousands of research articles. This research article is the first one, where blood vessel-directed therapy has a clear protective effect against the doxorubicin toxicity’, says Dr. Riikka Kivela, who supervised the study.

‘Our findings show, that especially the endothelial cells, which form the inner surface of the vessels in the heart, have an essential role in the protection against the cardiotoxicity. More preclinical studies are needed though for the development of VEGF-B gene therapy for cardiac protection in patients’, elaborates Rasanen.

University of Helsinki www.helsinki.fi/en/news/a-common-heart-problem-caused-by-cancer-therapy-avoided-blood-vessel-treatment

Insulin injection, if you’ve never done it, takes two hands. One hand holds the insulin injector. The other hand pinches the skin, to form a bulge so the hormone enters fat under the skin while avoiding muscle, where it can be absorbed quickly enough to cause a seizure.

‘Normally, you have an automatic pancreas,’ says Shawn Michels, a University of Wisconsin-Madison student and diabetic who has invented an add-on to insulin injectors, ‘but my pancreas is manual so I have to give myself injections when I want to reduce my blood sugar levels or eat food with carbohydrates.’

By definition, Type 1 diabetics do not make insulin. In Type 2 diabetes, the body does not respond properly to insulin.

Millions of diabetics around the world, both Type 1 and Type 2, have likely injected insulin billions of times into the easily accessible stomach and thighs. And many of them experience the side effect that bothered Michels – scarring and bruising – to some degree.

But Michels may be the only one who dwelled on the problem long enough to come up with a simple ‘Why didn’t I think of that?’ solution.

Insulin injectors use an ultrafine, mostly pain-free needle, but the need to use both hands during injection limits injections to the stomach and thighs.

Less than a year ago, after an estimated 10,000 injections, Michels dreamed up his ‘better idea’ while home on winter break. After discussions with his mother, an accountant, and his father, an executive at a roofing company, Michels decided to pursue his invention. ‘I have always been interested in business from a young age, and my parents were my first mentors,’ he says. ‘We talked about why some of my business ideas had potential, and why others didn’t.’

‘I could never inject into my arm, butt or back but now it’s a one-hand process. I gave my thighs and stomach a month to rest, and now I don’t have bruising or scar tissue.’

Michels has filed a patent and does not allow the device to be photographed, but clearly it is something that could be molded from plastic at low cost. Unless Food and Drug Administration approval is required, he hopes to be on the market in about six months.

Although the device could benefit any diabetic who injects, the initial market will be those with a new diagnosis, Michels says. ‘The first injection can be scary, and having an attachment that will hide the needle and regulate the depth should be helpful.’

University of Wisconsin-Madison news.wisc.edu/invention-could-help-diabetics-with-safer-surer-insulin-injections/

A tiny, transparent device that can fit into a contact lens has a bright future, potentially helping a range of scientific endeavours from biomedicine to geology.

Developed by Northwestern Engineering scientists, the device, called the Micro-ring resonator detector, can determine the speed of the blood flow and the oxygen metabolic rate at the back of the eye. This information could help diagnose such common and debilitating diseases as macular degeneration and diabetes.

The Micro-ring device builds upon Professor Hao F. Zhang’s ground-breaking work in 2006 to develop photo-acoustic imaging, which combines sound and light waves to create images of biological materials. The imaging technique is being widely explored for both fundamental biological investigations and clinical diagnosis, from nanoscopic cellular imaging to human breast cancer screening.

For three years, Zhang, associate professor of biomedical engineering, worked with Cheng Sun, associate professor of mechanical engineering, and their post-doctoral fellows Biqin Dong and Hao Li to create the Micro-ring resonator detector.

‘We believe that with this technology, optical ultrasound detection methods will play an increasingly important role in photo-acoustic imaging for the retina and many biomedical applications,’ Zhang said.

In 2006, Zhang was exploring new retinal imaging technologies when Dr. Amani Fawzi, now an associate professor of ophthalmology at Northwestern’s Feinberg School of Medicine, approached him to create a new diagnostic device that could measure biological activities at the back of the eye.

‘We needed a device that had large enough bandwidth for spatial resolution,’ Zhang said. ‘And it needed to be optically transparent to allow light to go through freely.’

‘Ultrasound detection devices of that time were usually bulky, opaque, and not sensitive enough. And they had limited bandwidth,’ Sun said. ‘It could only capture part of it what was happening in the eye.’

To meet Fawzi’s challenge, the team needed to develop a radically different type of detector – small enough to be used with human eyes, soft enough to be integrated into a contact lens and yet generate a super-high resolution of hundreds of megahertz.

‘The trouble was to fabricate it, have it fit in the size of a contact lens, and make it still work,’ Sun said.

First, the team considered a device that placed the needle-sized detector on the eyelid, but that method was not ideal. Next, they landed on the idea of a tiny ring implanted in a single-use contact lens worn during diagnosis.

However, that idea added an extra challenge – making the device transparent.

After nearly three years of work, they created the plastic Micro-ring resonator, a transparent device that is 60 micrometers in diameter and 1 micron high. There is movement toward using it with patients.

Northwestern University www.mccormick.northwestern.edu/news/articles/2017/02/new-method-to-detect-ultrasound-with-light.html

Researchers today unveiled results from a new blood test to help identify which patients are at an elevated risk of Alzheimer’s disease. The findings showed that the biochip test, which allows multiple tests to be run on one blood sample, was as accurate as existing molecular tests that analyse DNA.
‘This is the first time that we have used this biochip technology to test for an increased risk of Alzheimer’s disease,’ said Emma C. Harte, PhD, a research scientist. ‘This type of testing is important in our quest to understand and diagnose Alzheimer’s and empower patients to understand risks, consider medication, and even make early lifestyle changes.’
This test detects the presence of a protein in the blood produced by a specific variation of the apolipoprotein gene (ApoE4), which is associated with increased risk of developing Alzheimer’s disease. The apolipoprotein gene is inherited from each parent and when a patient inherits the ApoE4 variant from one parent they have a three times greater risk of developing Alzheimer’s disease, whereas a patient who inherits ApoE4 from both parents is eight-to-12 times more likely to develop the disease.
To verify the accuracy of the biochip test, 384 samples were analysed and results compared to those from a standard molecular diagnostic test. Researchers from Randox Laboratories collaborated with research colleagues at the Medical University of Vienna and found that results from the two tests were in 100percent agreement. As biochip tests allow clinicians and researchers to quickly run multiple tests on one sample of blood, this new test is also faster and more affordable than the standard DNA test, producing results in only three hours. This enables doctors to predict the risk of an individual developing Alzheimer’s disease.
‘Pairing this test with medical and family history for risk of Alzheimer’s disease has the real potential to advance personalized medicine,’ said Harte. ‘This fast, accurate testing will allow doctors and patients to make more informed choices earlier to potentially slow the possible progress of Alzheimer’s.’

AACC http://tinyurl.com/zeamaf2

Administration of the amino acid D-serine, a dietary supplement, contributes to the improvement of the cognitive and motor capacity of a patient with a mutation that affects glutamate receptors
A translational, multicenter study carried out by research groups of the Bellvitge Biomedical Research Institute (IDIBELL), San Juan de Dios Hospital (HSJD), the University of Barcelona (UB), Clinic Hospital (IDIBAPS), the University of Vic (UVic), Santa Creu i Sant Pau Hospital (IIB Sant Pau) and the thematic area of Rare Diseases (CIBERER), has unveiled the potential of D-serine – a dietary supplement – to improve the neuronal function of a patient with a mutation of the glutamate receptors associated to atypical Rett syndrome with severe encephalopathy. This collaborative study, led by Dr. Xavier Altafaj (Neuropharmacology Unit, IDIBELL), opens a new range of therapeutic options for patients with mutations that affect glutamatergic neurotransmission. Likewise, this study has allowed to establish a unique and novel experimental approach that is currently being transferred to an ambitious project that aims to design predictive algorithms that lead to personalized treatments that can be quickly transferred to the clinical practice for other mutations that affect glutamatergic transmission.
"The story begins about three years ago, when Dr. Ángeles García-Cazorla, a neuropediatrician at San Juan de Dios Hospital and professor at the University of Barcelona, contacted us regarding one of his patients, who presented an atypical form of Rett syndrome with severe encephalopathy”, explains Dr. Xavier Altafaj, leader of the study and member of the Neuropharmacology Unit IDIBELL-UB, led by Dr. Francisco Ciruela. While assessing the exome of this patient,  the geneticists of San Juan de Dios (Dr. Judith Armstrong) identified a mutation that affects the coding gene for a subunit of glutamate receptors of the NMDA type. "Our research group is specialized in the study of these type of receptors, which in physiological conditions are associated with learning processes, memory, neurodevelopment and neuronal plasticity, and which are the main actors in excitatory transmission and neuronal function”, Altafaj adds.
The HSJD medical team and Dr. Altafaj’s group were interested in finding out whether the patient’s mutation could be responsible for for her disability to some extent. To do so, the team of Dr. David Soto (UB-IDIBAPS) carried out several functional studies that allowed them to prove that the mutation drastically reduces the activity of the glutamate channel. With these results, the group of Dr. Altafaj started a second battery of cellular, physiological and biochemical studies with the participation of Dr. Carles Sindreu (UB), Dr. Àlex Bayés (IIB Sant Pau) and Dr. Francisco Ciruela (IDIBELL-UB), to characterize the consequences of the loss of function of mutated receptors.
At the same time, computational studies conducted by Dr. Mireia Olivella (UVic) revealed that the mutation of the glutamate receptor sequence – potentially responsible for the patient’s symptoms – modified the receptor structure, decreasing the size of the canal’s pore and thus its affinity for glutamate, as it was subsequently validated at the experimental level. Glutamate is the main excitatory neurotransmitter of the central nervous system; Consequently, if the channel activity of this receptor is impaired, calcium intake could be reduced, leading to a clear decrease in neuronal function.
"Bearing everything in mind, we had two options," says Dr. Altafaj: "either we spent years designing a personalized drug or therapeutic approach to specifically correct the hypophysiologicality of the affected receptors, or we looked for an existing drug or compound able to increase the functionality of these receptors, forcing their activity and improving calcium intake. We were faced with a time-dependent situation, since neurodevelopmental processes are critical at the patient’s age, and consequently we went for the second option."
In order to be activated, NMDA receptors require the simultaneous presence of glutamate and the amino acids glycine or serine, which act as co-agonists. Knowing that glycine also acts on other types of receptors, IDIBELL researchers proposed to administer D-serine – an already commercialized dietary supplement, easy to administer and without side effects – to improve receptor activation and rebound glutamatergic transmission. In vitro studies in cell lines and primary cultures showed that D-serine supplementation enhanced the activity of mutated receptors. These results led Dr. Ángeles García-Cazorla, with the consent of the patient’s parents, to start a D-serine supplemented diet.
Follow-up of the patient by the Drs. Ángeles García-Cazorla and Anna López (HSJD showed that dietary supplementation with D-serine can be associated with significant improvements in the patient’s symptoms, both at a motor and cognitive level. "The patient is able to develop basic motor tasks that were unthinkable of at the beginning of the treatment, 17 months ago. We could say that the patient is connected to the outside world that surrounds her, and this represents a critical and unavoidable step towards establishing new neuronal connections", Dr. Altafaj describes.
The researchers are cautious but optimistic at the same time: "the results that we observe in the patient after a year and a half are very promising and we hope that she continues to improve, but we must also bear in mind that they are the consequence of a combined effort of several therapeutic interventions. In addition to treatment with D-serine, neuro-stimulation therapies have also been implemented and parents have been able to create a very positive development environment that is also contributing. However, prior experience with similar clinical cases had not shown improvements that significant, and in this sense this study makes us feel very optimistic and encourages us to keep following this direction. "

Bellvitge Biomedical Research Institute (IDIBELL),
www.idibell.cat/modul/news/en/1007/a-personalized-treatment-with-metabolic-therapy-improves-the-motor-and-communication-skills-of-a-patient-with-atypical-rett-syndrome