In the News
Anisina Confirmed as Effective Anti-Cancer Agent in Animal Studies
US-Australian drug discovery company, Novogen, has announced that it has confirmed that drug candidate, Anisina, is an effective monotherapy against human melanoma in an animal model.
The company announced recently that Anisina was a potent cytotoxic in vitro against human melanoma cells, and in particular that this effect was unaffected by the mutational status of the melanoma cells, particularly the common Braf gene status.
The purpose of the pre-clinical study was to provide evidence that this potent anti-cancer effect could be transferred to the whole animal. Such evidence is required to justify conducting human clinical studies in adults with solid cancers such as melanoma. The company previously has announced the effectiveness of Anisina as a monotherapy in mice bearing human neuroblastoma tumors, thereby justifying taking it into clinical trials in children and juveniles with solid cancers such as neuroblastoma. Taken together, the two results confirm the potential clinical benefit of this drug across both adult and pediatric cancers.
In the current study, highly chemo-resistant human melanoma cells were grown in athymic mice and the animals treated either orally or intravenously with Anisina. Both dosage forms were equally effective.
Novogen anti-tropomyosin program director Justine Stehn, PhD, said, "We are pleasantly surprised by the degree of anti-tumor activity of this drug candidate on its own. We had always seen the anti-tropomyosin technology as being an adjunct therapy for the more commonly used anti-mitotic drugs. The rationale behind its development was to destroy that half of a cancer cell's cytoskeleton that the anti-mitotic drugs didn't target. We reasoned that destabilizing the entire cytoskeleton would achieve a much higher level of anti-cancer effect than that coming from targeting either half alone. And, indeed, that is what we see. Anisina used in combination with anti-mitotic drug, vincristine, increases the anti-cancer potency of vincristine 20-fold."
Stehn added, "Despite all the evidence showing that Anisina has the potential to be just as effective a stand-alone chemotherapy as the anti-mitotic drugs, we still intend to see Anisina as a companion drug for an anti-mitotic drug. The initial patients, however, will need to be treated with Anisina on its own, and this study now gives us the green light to proceed into a Phase 1 study in the first half of 2016."
In preparation for both adult and paediatric clinical studies, the Company is conducting studies in a variety of both adult and paediatric solid and non-solid cancer types in order to determine the optimal drug combination. Data of the effectiveness of Anisina in combination with vincristine in animals bearing human neuroblastoma tumors is being presented to a conference in July 2015.
Graham Kelly, Novogen Group CEO, said, "Each step in the drug development process continues to build our confidence in the potential for this exciting first-in-class drug. The fact that we know its target and how it works; the fact that it is making the most commonly used drugs in chemotherapy work 20 times better, as well as looking like we can extend the effectiveness of the combination into tumor types traditionally unresponsive to anti-mitotic drugs; the fact that, in the case of melanoma anyway, its effectiveness is unaffected by mutational status; and the fact that it can be delivered conveniently by the oral route and in that form was well tolerated by animals with no observed side-effects: All these factors point to a highly versatile and promising new drug candidate with potentially broad application across the cancer spectrum."
Source: Novogen Ltd, novogen.com
The Metagenics Healthcare Institute for Clinical Nutrition Launches Educational Website
On April 2nd, Metagenics Healthcare Institute for Clinical Nutrition launched an educational resource for all healthcare providers with roots in integrative, traditional and functional medicine. The purely educational and non-promotional website is sponsored by Metagenics, a leader in the field of clinical nutrition and innovation in healthcare. The site was developed to provide the most current, evidence based information, peer reviewed publications, data and tools on clinical nutrition and lifestyle medicine from leading authorities and collaborating research institutions from across the globe.
Complimentary, AMA category 1, continuing education credits in clinical nutrition are also offered to registered users. According to Metagenics Chief Science Officer and President, Metaproteomics Research Division, John Troup, PhD, "Research has shown physicians spend more than 70% of their time using online resources for clinical decision making; this site is intended to support them with credible and relevant information as they improve patient outcomes and reduce healthcare utilization."
The website, accessible across various platforms, will feature regular healthcare campaigns to increase awareness about specific health issues and offer guidance for nutrition based solutions. The current campaign, Gut Check! offers registered users an opportunity to explore the importance of a healthy microbiome and precision probiotics via podcasts, downloadable slides and videos from recent symposia presented at Clinical Nutrition Week 15 from the American Society for Parenteral and Enteral Nutrition (ASPEN), as well as the TEDTalk from noted speaker, Rob Knight, PhD on "How Our Microbes Make Us Who We Are." Other health campaigns being planned for 2015 will focus on women's health, with others scheduled throughout the year that will address Type 2 Diabetes and Inflammation.
You can find the Metagenics Healthcare Institute for Clinical Nutrition at mhicn.com. Register and login to gain full access to various modules, videos and podcasts and to receive regular updates by email.
SOURCE Metagenics Healthcare Institute for Clinical Nutrition
Major Alzheimer's Risk Gene Opens New Pathway to Prevention
In a groundbreaking new study, researchers from the Blanchette Rockefeller Neurosciences Institute (BRNI) have discovered that the Apolipoprotein E4 (ApoE4) gene, the major genetic risk factor for the vast majority of late, age-dependent Alzheimer's patients, can reduce the number of mature, functional synapses in the brain by interfering with the DNA responsible for synapse formation and maintenance. Synaptic loss, a key element of Alzheimer's disease, often occurs before the onset of amyloid plaques or tangles in Alzheimer's patients. This new finding could potentially shift current thinking around Alzheimer's disease—from treatment of the disease to prevention.
In the study published May 13 in the Journal of Neuroscience, scientists found that the ApoE4 gene increases nuclear translocation and activity of histone deacetylases (HDACs) in human neurons. (HDACs are enzymes that act like on/off buttons for genes.) This activity reduces levels of DNA-programmed brain-derived neurotrophic factor (BDNF), which is a critical component in the formation, repair and plasticity of synapses between brain cells. The loss of mature, functional synapses is a key element of early Alzheimer's disease and its associated cognitive deficits.
"We know that people with the complete ApoE4 genes are 10 times more likely to suffer from the most common form of late, age-dependent Alzheimer's disease. We also know from previous autopsy studies that Alzheimer's patients have deficits of BDNF, Protein Kinase C (PKC) epsilon and synapses," said Dr. Daniel Alkon, Scientific Director of BRNI. "Now, in the present study, the brains of Alzheimer's patients were found to have increased levels of HDACs. These findings, taken together, suggest that substituting the abnormal ApoE4 gene for the ApoE3 gene is one of the earliest causes of synaptic loss in Alzheimer's disease."
A Shift in Thinking around Alzheimer's
To date, every single late-phase clinical trial for Alzheimer's drugs—even those that held promise in preclinical studies—has failed. The majority of these studies has focused on the pathologic hallmarks of brains of Alzheimer's sufferers, particularly on sticky extracellular clumps of proteins and cellular debris known as "amyloid plaques," and twisted intracellular tau fibers, often referred to as "tangles."
"Our study provides evidence for a major shift in current thinking around Alzheimer's disease and research," said Dr. Alkon. "Synaptic loss often occurs before the onset of amyloid plaques or tangles in Alzheimer's patients, so our latest findings suggest that many of today's trials that only focus on plaques and tangles aren't targeting a critical pathway responsible for early synaptic loss and, therefore, Alzheimer's disease."
A Pathway to Prevention
But there may be hope for prevention. BRNI has shown in pre-clinical studies that activating PKC with potent activators such as Bryostatin can prevent ApoE4 from inhibiting BDNF production. Bryostatin, by increasing PKC epsilon, has also been shown in previous pre-clinical studies to lower soluble A Beta oligomers that lead to plaque formation. Since A Beta oligomers also function like ApoE4 to interfere with DNA-controlled BDNF production through HDACs, Bryostatin could potentially block this A Beta oligomer effect as well. This would offer further Alzheimer's disease prevention potential. Elevated HDACs, lower PKC epsilon, reduced BDNF and increased A Beta oligomers, working together, compromise synaptic function, growth and maintenance in the absence of amyloid plaques and tangles.
Discoveries from the present study suggest that these same PKC activators in trials to treat Alzheimer's disease patients could potentially be given to healthy individuals who have the ApoE4 genes – even before Alzheimer's disease begins – thereby preventing the onset of debilitating dementia and brain degeneration.
"We are excited and encouraged by these results," said Alkon. "In essence, our findings suggest that Bryostatin could be used in some patients to prevent Alzheimer's disease before it ever begins."
To read BRNI's full study, visit jneurosci.org/content/35/19/7538.abstract
Study Shows Pycnogenol Can Help Improve Endothelial Function
New research reports further natural solutions for those at heightened risk of coronary artery disease (CAD)—the No. 1 killer in America. A study published in the Journal of International Angiology found that daily supplementation of Pycnogenol (pic-NOJ-en-all), a standardized natural plant extract from French maritime pine tree bark, may help improve endothelial function for those with borderline hypertension, hyperglycemia, or hyperlipidemia. The study showed Pycnogenol to be effective in helping to normalize blood pressure, manage LDL cholesterol, and reduce oxidative stress levels.
Nearly 70 million Americans suffer from hypertension, which can be stimulated by endothelial dysfunction—a condition in which the inner lining of blood vessels does not function normally. Endothelial dysfunction can result from and contribute to several cardiovascular diseases such as hypertension, diabetes, and septic shock.
"Approximately 85 million Americans suffer from some form of cardiovascular disease. Endothelial cells play a crucial role in defending against CAD and ensuring proper blood flow through our blood vessels. This study finds Pycnogenol may be a useful addition for patients with endothelial dysfunction who have borderline hyperglycemia, hypertension, and hyperlipidemia," said Dr. Steven Lamm, a physician and nutritional medicine expert. "For those with increased CAD risk, this kind of alternative can be an important step in avoiding development of serious heart conditions."
The peer-reviewed study conducted at Chieti-Pescara University in Italy included 92 participants with borderline hyperlipidemia, hypertension, or hyperglycemia between ages 40 and 60, all of whom were generally fit and followed a healthy lifestyle.
In the study, 49 participants supplemented Pycnogenol 50mg/three times daily in combination with a controlled health plan; 43 participants in the control group followed the controlled health plan alone. The health plan involved a reduction of carbohydrates and caffeinated drinks and daily exercise. While there is no defined treatment for endothelial dysfunction, lifestyle patterns and daily exercise routines have shown to lower cholesterol levels.
Subjects were evaluated at 8 and 12 weeks. Daily supplementation with Pycnogenol was shown to:
>>Significantly improve endothelial function (55 percent after 8 weeks of supplementation; 66 percent after 12 weeks of supplementation)
>>Significantly reduce oxidative stress by 20 percent
>>Normalize blood pressure in subjects with borderline hypertension
>>Reduce cholesterol levels in participants with borderline hyperlipidemia
>>Improve fasting glucose levels in the group with borderline high glucose levels
"This study builds on previous research showing that Pycnogenol can play a role in helping to reduce platelet aggregation, blood pressure, and oxidative stress. There have been a number of studies proving Pycnogenol's effectiveness in helping to lower LDL cholesterol levels, normalize capillary blood vessels morphology and function, and overall, improve blood circulation. A study from 2012 at the University Hospital Zurich has already established the improvement of endothelial function in people with coronary artery disease. These new findings show and confirm that Pycnogenol can help improve overall endothelial function—an important area of research for millions of patients and an essential step in the progression of pre-clinical atherosclerosis—especially those with borderline hyperglycemia and hyperlipidemia or borderline hypertension," said Dr. Gianni Belcaro, lead researcher of the study.
Endothelial function was measured using a flow-mediated-dilation (FMD) and laser Doppler for the assessment of the distal finger flux. In addition plasma free radicals (PFR) metabolic parameters and blood pressure were evaluated. When Pycnogenol was added to a controlled health plan, endothelial function improved by 66 percent over a 12-week period.
Pycnogenol improvement of endothelial function can be explained by its ability to activate the enzyme endothelial nitric oxide synthase (eNOS), present in endothelial cells, to more efficiently generate nitric oxide (NO) from the precursor amino acid L-arginine.
This study further strengthens Pycnogenol's robust portfolio of heart health benefits and provides additional support that the antioxidant is a safe, natural option for those dealing with cardiovascular problems. Past clinical trials have shown beneficial effects of Pycnogenol on chronic inflammation as well as cardiovascular risk factors including endothelial function, hypertension, cholesterol, and platelet function.
Source: Horphag Research Ltd., pycnogenol.com
New Technology Enables Real-Time Monitoring of Protein Interactions in Live Cells
Promega Corporation has announced the launch of NanoBRET Protein Interaction Assays, which use a new Bioluminescence Resonance Energy Transfer (BRET) technology that enables scientists to quantitatively measure protein-to-protein interactions in live cells.
Traditional methods for studying interactions between proteins are commonly performed in vitro using only protein fragments and do not provide data in the context of the cellular environment. With NanoBRET Protein Interaction Assays, researchers can study both induction and inhibition of protein interactions in real time using full-length proteins expressed at physiologically relevant levels.
Conventional BRET measures the interaction of proteins using a bioluminescent donor fused to a protein of interest and a fluorescent acceptor fused to its binding partner; the donor does not excite the fluorophore using light, but transfers resonance energy through dipole-dipole coupling. The optimized NanoBRET Protein Interaction Assays use NanoLuc Luciferase as the energy donor and HaloTag protein as the energy acceptor. NanoBRET Technology has improved spectral overlap, increased signal, and lower background, providing researchers with a reproducible method for monitoring and screening protein interactions. In addition, the brighter light output from NanoLuc enables use of NanoBRET even at low expression levels, while still providing efficient energy transfer.
To learn more about NanoBRET Protein Interaction Assays visit: promega.com/NanoBRET-PPItechnology
New Research Shows Positive Impact of Technology on Dementia Patients
Individuals living with dementia can benefit from technology, especially when aided by family members, according to a University of Washington case study published in the Journal of Gerontological Nursing in April.
The case study, titled "Involving Family Members in the Implementation and Evaluation of Technologies for Dementia," followed the progress of an 80-year-old dementia patient at a memory care unit as she used recreational technology from It's Never 2 Late (iN2L) with assistance from her 56-year-old daughter. The iN2L technology used included a touch screen computer, numerous applications to facilitate physical activity and cognitive memory, and additional components such as a joystick, camera, and hand bike.
The study reported a number of key observations:
>>The daughter's close involvement and input was effective in designing and deploying technology tailored to her mother's personal interests.
>>The mother experienced particular satisfaction using technology with a family member.
>>Using technology together may be a way to foster more interaction between relatives and dementia patients.
Most notably, the mother's score on the Mini-Mental State Examination increased from 16 (indicating moderate dementia) to 21, a distinct improvement.
"Empirical research continues to demonstrate what we've recognized for years and is the singular purpose driving iN2L—technology that is thoughtfully designed to the needs of people living with dementia considerably improves their quality of life," said Juliet Kerlin, research director of iN2L. "In fact, it provides caregivers with opportunities to support and maximize the residents' unique strengths. As we can see from this study, such technology also revives engagement and strengthens connections with family members."
The study’s findings come closely on the heels of a research study released by the LeadingAge Center for Aging Services Technologies (CAST), "Reducing the Use of Psychotropic Drugs and Improving Quality of Life Through Entertaining Technology-Driven Activities," which concluded that personalized technology effectively lowers prescription drug use for older adults living with dementia.
"It's rewarding to have objective research back up what we have seen for 16 years, that person-centered technology can positively impact the lives of people dealing with dementia," commented Jack York, CEO of iN2L. "Having a positive impact on families is a huge part of our success. Everyone, including family members, tend to make assumptions regarding the limitations of someone with the disease. These assumptions are shattered when user-friendly technology intersects with individualized content."
Several research studies are planned or underway at the University of Maryland (Baltimore County), University of Indiana, and Xavier University to quantify the benefits of the iN2L system when used for structured recreational and leisure activities in nursing home settings, as well as to reduce the behavioral and psychological symptoms of dementia (BPSD) in memory care settings.
Source: iN2L, iN2L.com
Mental Health Month Highlights Need for Holistic Approach to Patient Care
DaVita Kidney Care, a division of DaVita HealthCare Partners Inc. and a leading provider of kidney care services, recognizes the month of May as Mental Health Month. It brings light to the struggles of people living with invisible illnesses like depression and the difficulties in overcoming those adversities.
"People with kidney disease and their caregivers may find themselves facing depression as they adjust to life on dialysis," said Duane Dunn, director of social work services at DaVita Kidney Care. "In the words of one of our patients, 'dialysis isn't an easy thing to go through, but end-stage renal disease isn't end stage—it's just another stage in your life.'"
Discovering a sense of purpose can be fundamental to a high quality of life on dialysis, especially as people first adjust to life on dialysis and re-enter their communities with new challenges. Whether that purpose derives from working, volunteering, parenting, attending school, or other hobbies and interests, the important part is to find the motivation to thrive on dialysis.
For both patients and their caregivers, resource access is a critical component in managing mental health. Here are some tips for thriving while on dialysis:
>>Openly discuss – Talk with your nephrologist and social worker because they understand where patients struggle most in adjusting and coping to life on dialysis.
>>Seek counseling – Outpatient services are available in a variety of different agencies and can be accessed by the local Department of Human Services.
>>Find a support group – Look for support groups that can understand and empathize with what's happening. There are local in-person support groups as well as online options that can help provide guidance.
>>Seek kidney disease education – Attending a kidney disease education class allows attendees to ask questions about kidney disease and get an understanding of life on dialysis.
>>Continue to work – Dialysis patients who continue to work are 21 percent less likely to experience symptoms of depression, according to a study published in the Clinical Journal of the American Society of Nephrology. Working may provide a sense of purpose and a positive distraction from dialysis, all of which help contribute to a better quality of life.
DaVita Kidney Care recently launched its Empowering Patients Program, which is designed to enhance social workers' skill sets to further help improve patients' quality of life through behavioral activation, mindfulness, and coping skills. A poster on this program was presented during the National Kidney Foundation Spring Clinical Meeting in April 2015 and was recognized as a "Healthcare Professional Top Poster." The poster highlighted symptom-targeted interventions (STI) by social workers to help decrease patients' missed dialysis treatments. Aspects of the program included deep breathing, coping thoughts, and behavior activation. Results suggest that a social-worker-based STI program improved quality of life for patients involved.
DaVita Kidney Care has shown itself to be a leader in putting quality at the forefront of the conversation. This has been recognized by the Center for Medicare and Medicaid Services (CMS) with the Five-Star Rating System and CMS' Quality Incentive Program (QIP). DaVita Kidney Care was recognized with 50 percent of its centers receiving a four- or five-star rating. With QIP, 98.5 percent of DaVita Kidney Care's centers rated among the top clinical performance tiers in the country.
Source: DaVita Kidney Care, davita.com
GlassesOff Announces Positive Results From ADHD Study
GlassesOff Inc. has announced the results from a study in children and adults with attention deficit hyperactivity disorder (ADHD), demonstrating non-invasive, game-like technology that can provide an early indication of whether a child has ADHD and to what degree. In addition, once a child has been prescribed an ADHD medication, the GlassesOff tool may be able to be utilized as a monitor to provide insight as to whether the medication and/or its dosing are effective, or should be modified. GlassesOff intends to develop a dedicated ADHD commercial application following results of the study.
The findings from a new study from GlassesOff show significant differences in the visual performance of children and adults with ADHD, compared with children and adults who do not have ADHD, with respect to specific visual tasks. A new GlassesOff application may be able to quantitatively measure these differences as a quantitative way to screen for the disorder.
The study included 45 adults, 28 of them previously diagnosed with ADHD, and 64 children, 21 of them previously diagnosed with ADHD, all of whom had no history of neurological conditions and normal or corrected-to-normal vision in both eyes. Measurements were made on smartphones, using a prototype dynamic digital assessment tool developed by GlassesOff, and results were compared between participants with and without ADHD. The results of this research showed a significant distinction in the visual performance of participants diagnosed with ADHD, despite having normal 20/20 or better visual acuity on the clinical optometric chart, compared with participants who did not have ADHD.
Nimrod Madar, CEO of GlassesOff, said, "We believe that our scientific team is at the forefront of understanding the correlation between visual functions and the diagnosis of various neurobehavioral conditions. This pioneering technology could become the base for the first self-administered objective screening tool for ADHD."
Mr. Madar went on to say, "We trust that this technology can become a simple tool for any parent to know if a child needs to seek medical help to professionally diagnose ADHD; and this technology may additionally provide invaluable information to parents and physicians regarding the efficacy of the medication post initiation of ADHD drug therapy."
According to the Centers for Disease Control and Prevention, ADHD is one of the most common neurobehavioral disorders, impairing the quality of life for millions of children and adults. In spite of this, there is no simple way to diagnose the disorder. Currently, diagnosis requires specialized clinicians engaging in a long, several-step process using qualitative tools. For children in particular, the diagnosis can be significantly misguided by subjective input from parents.
GlassesOff presented the findings from the study yesterday at the international annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Denver, Colorado. The presentation can be viewed at glassesoff.com/wp-content/uploads/2015/05/GlassesOff-ADHD-Study-Results.pdf.
Source: GlassesOff Inc., glassesoff.com