Feeds:
Posts
Comments

Posts Tagged ‘World Health Organization’


Live 12:00 – 1:00 P.M  Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

12.00 The Italian Mediterranean Diet as a Model of Identity of a People with a Universal Good to Safeguard Health?

Prof. Antonino De Lorenzo, MD, PhD.

Director of the School of Specialization in Clinical Nutrition, University of Rome “Tor Vergata”

It is important to determine how our bodies interacts with the environment, such as absorption of nutrients.

Studies shown here show decrease in life expectancy of a high sugar diet, but the quality of the diet, not just the type of diet is important, especially the role of natural probiotics and phenolic compounds found in the Mediterranean diet.

The WHO report in 2005 discusses the unsustainability of nutrition deficiencies and suggest a proactive personalized and preventative/predictive approach of diet and health.

Most of the noncommunicable diseases like CV (46%) cancer 21% and 11% respiratory and 4% diabetes could be prevented and or cured with proper dietary approaches

Italy vs. the US diseases: in Italy most disease due to environmental contamination while US diet plays a major role

The issue we are facing in less than 10% of the Italian population (fruit, fibers, oils) are not getting the proper foods, diet and contributing to as we suggest 46% of the disease

The Food Paradox: 1.5 billion are obese; we notice we are eating less products of quality and most quality produce is going to waste;

  •  growing BMI and junk food: our studies are correlating the junk food (pre-prepared) and global BMI
  • modern diet and impact of human health (junk food high in additives, salt) has impact on microflora
  • Western Diet and Addiction: We show a link (using brain scans) showing correlation of junk food, sugar cravings, and other addictive behaviors by affecting the dopamine signaling in the substantia nigra
  • developed a junk food calculator and a Mediterranean diet calculator
  • the intersection of culture, food is embedded in the Mediterranean diet; this is supported by dietary studies of two distinct rural Italian populations (one of these in the US) show decrease in diet
  • Impact of diet: have model in Germany how this diet can increase health and life expectancy
  • from 1950 to present day 2.7 unit increase in the diet index can increase life expectancy by 26%
  • so there is an inverse relationship with our index and breast cancer

Environment and metal contamination and glyphosate: contribution to disease and impact of maintaining the healthy diet

  • huge problem with use of pesticides and increase in celiac disease

12:30 Environment and Health

Dr. Iris Maria Forte, PhD.

National Cancer Institute “Pascale” Foundation | IRCCS · Department of Research, Naples, Italy

Cancer as a disease of the environment.  Weinberg’s hallmarks of Cancer reveal how environment and epigenetics can impact any of these hallmarks.

Epigenetic effects

  • gene gatekeepers (Rb and P53)
  • DNA repair and damage stabilization

Heavy Metals and Dioxins:( alterations of the immune system as well as epigenetic regulations)

Asbestos and Mesothelioma:  they have demonstrated that p53 can be involved in development of mesothelioma as reactivating p53 may be a suitable strategy for therapy

Diet, Tomato and Cancer

  • looked at tomato extract on p53 function in gastric cancer: tomato extract had a growth reduction effect and altered cell cycle regulation and results in apoptosis
  • RBL2 levels are increased in extract amount dependent manner so data shows effect of certain tomato extracts of the southern italian tomato (     )

Antonio Giordano: we tested whole extracts of almost 30 different varieties of tomato.  The tomato variety  with highest activity was near Ravela however black tomatoes have shown high antitumor activity.  We have done a followup studies showing that these varieties, if grow elsewhere lose their antitumor activity after two or three generations of breeding, even though there genetics are similar.  We are also studying the effects of different styles of cooking of these tomatoes and if it reduces antitumor effect

please see post https://news.temple.edu/news/2017-08-28/muse-cancer-fighting-tomatoes-study-italian-food

 

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles


@S_H_R_O 

@SbarroHealth

@Pharma_BI 

@ItalyinPhilly

@WHO_Europe

@nutritionorg

# hashtags


#healthydiet

#MediterraneanDiet

#health

#nutrition

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

Real Time Conference Coverage for Scientific and Business Media: Unique Twitter Hashtags and Handles per Conference Presentation/Session

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT

Real Time Coverage and eProceedings of Presentations on 11/16 – 11/17, 2016, The 12th Annual Personalized Medicine Conference, HARVARD MEDICAL SCHOOL, Joseph B. Martin Conference Center, 77 Avenue Louis Pasteur, Boston

Tweets Impression Analytics, Re-Tweets, Tweets and Likes by @AVIVA1950 and @pharma_BI for 2018 BioIT, Boston, 5/15 – 5/17, 2018

BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

HUBweek 2018, October 8-14, 2018, Greater Boston – “We The Future” – coming together, of breaking down barriers, of convening across disciplinary lines to shape our future

Read Full Post »


Food Insecurity in Africa and GMOs

Reporter and Curator: Larry H. Bernstein, MD, FCAP 

 

This Report is a presentation from several articles since mid-2013 on the food shortage in Sub-Saharan Africa, where crop yields are among the lowest in the worlds.  In this series we have presented modiable  and epigenetic causes of CVD, among other topics, including diabetes, obesity, and exercise.  We have mentioned that while magnesium, fiber, a sufficient source of n-3 polyunsaturated fatty acids (from seafood or seaweed, or from flaxseed), and a functional methyl transporter as well as a source of methionine ( which requires a meat source, as B9 folate is plant sourced and does not fix the problem).  In this discussion we have both a voluntary and an involuntary course of living that leads to CVD and brain dysfunction, depending on where one lives, a “perfect storm”.

Part 1.  Tensions over Food Insecurity in Africa   Oct 8, 2013

Sharon Schmickle

Sub-Saharan Africa’s agricultural yields are among the lowest in the world, and nearly one-third of its people are malnourished. That much, tragically, is well established. Less clear are the reasons Africa’s farm output remains depressed despite hands-on work and billions of dollars invested by individuals, organizations and governments. News reports often explore specific aspects of the problem such as drought. This series takes the novel approach of looking at intertwined tensions underlying the many problems. Through stories told across the continent, Sharon Schmickle focus on several key themes:

  • Africa is caught in an ideological struggle over the nature and scope of agriculture with European—and, sometimes, American—organizations pitted against agribusiness and many agricultural scientists.
  • Institutions have failed African farmers. Public and private agencies often work at cross purposes, neglecting to follow through on crop-saving opportunities. Investments in research and agricultural extension have been inadequate.

Scientists have made impressive gains against the scourges that threaten crops. But they risk losing their breakthroughs against malnutrition, crop-destroying pests and drought if they overlook local tastes and customs.

The series, which also incorporates the work of local journalists, begins with an overview of Tanzania where government officials are divided in the global ideological standoff. Despite a government initiative called Kilimo Kwanza (Farmers First), many farmers lack access to the improved seeds and tissue cultures that could help them thwart yield-stealing diseases and pests. And many farmers are so locked into practices of the past that change comes hard if at all.

This narrative is not twisted to an anti-GMO slant, and could be viewed as a need for GMO harvests without the independence to develop them, and the struggle against a powerful industrial source that takes from an impoverished people.

Sharon Schmickle has been a journalist for MinnPost.com since 2007, and before that she worked for the Minneapolis Star Tribune where she reported from the paper’s Washington bureau…

http://pulitzercenter.org/sites/default/files/styles/responsive_cropped/public/09-16-13/1382/lunch_line_at_engaruka_primary_school_0.jpg

Roiling tensions underlie efforts to improve food security in Africa, often pulling at cross purposes on farmers, consumers and their countries.

Tanzania: Mixed Feelings on Genetically Modified Crops
Tanzania faces the question of whether food from GM crops will sell at markets like this one in Dar es Salaam. Image by Sharon Schmickle. Tanzania, 2013.

Part 2.  Nathanael Johnson lets the anti-GMO movement off the hook

By MICHAEL EISEN | Published: JAN 10, 2014

For the last six months, Nathanael Johnson has been writing about GMOs for the lefty environmental magazine Grist. The goal of his ultimately 26 part series was to try and bring some journalistic sanity to a topic that has gotten nasty in recent years. As Grist editor Scott Rosenberg is quoted on Dan Charles’ blog:
GMOs “were a unique problem for us,” says Rosenberg. On the one hand, most of Grist’s readers and supporters despise GMOs, seeing them as a tool of corporate agribusiness and chemical-dependent farming.

On the other hand, says Rosenberg, he’d been struck by the passion of people who defended this technology, especially scientists. It convinced him that the issue deserved a fresh look.

I’ve enjoyed reading the series. Johnson has investigated a wide range of issues related to GMOs with a generally empirical eye – trying to find data to help answer questions, while avoiding the polemicism that dominates discussions of the topic. Although I don’t think everything he has written is right, the series is a very useful starting point for people trying to wrap the heads around what can be a complex topic. He has clearly tried to delve deeply into every topic, and to not let dogma or propaganda from either side affect his conclusions.

Unfortunately, if the series has had an effect on what I presume is its target audience – the anti-GMO readers of Grist – it hasn’t shown up in online debates about GMOs. When I and others have pointed to Johnson’s series in response to outrageous statements from anti-GMO campaigners, he is dismissed as either a naive fool or just another Monsanto tool.

So I was surprised to read his concluding piece in the series, “What I learned from six months of GMO research: None of it matters“.

The most astonishing thing about the vicious public brawl over GMOs is that the stakes are so low.

His basic point is that a lot of hot air and political energy is spent trying to decide between two alternative futures that aren’t all that different.

In the GMO-free future, farming still looks pretty much the same. Without insect-resistant crops, farmers spray more broad-spectrum insecticides, which do some collateral damage to surrounding food webs. Without herbicide-resistant crops, farmers spray less glyphosate, which slows the spread of glyphosate-resistant weeds and perhaps leads to healthier soil biota. Farmers also till their fields more often, which kills soil biota, and releases a lot more greenhouse gases.

The banning of GMOs hasn’t led to a transformation of agriculture because GM seed was never a linchpin supporting the conventional food system: Farmers could always do fine without it. Eaters no longer worry about the small potential threat of GMO health hazards, but they are subject to new risks: GMOs were neither the first, nor have they been the last, agricultural innovation, and each of these technologies comes with its own potential hazards. Plant scientists will have increased their use of mutagenesis and epigenetic manipulation, perhaps. We no longer have biotech patents, but we still have traditional seed-breeding patents. Life goes on.

In the other alternate future, where the pro-GMO side wins, we see less insecticide, more herbicide, and less tillage. In this world, with regulations lifted, a surge of small business and garage-biotechnologists got to work on creative solutions for the problems of agriculture.

Genetic engineering is just one tool in the tinkerer’s belt. Newer tools are already available, and scientists continue to make breakthroughs with traditional breeding. So in this future, a few more genetically engineered plants and animals get their chance to compete. Some make the world a little better, while others cause unexpected problems. But the science has moved beyond basic genetic engineering, and most of the risks and benefits of progress are coming from other technologies. Life goes on.

In many ways he’s right. GMOs on the market today – and most of the ones planned – are about making agriculture more efficient and profitable for farmers and seed providers. This is not a trivial thing, but would global agriculture collapse without these GMOs? Of course not.

We rarely see transformative technologies coming. And remember that we are still in the very early days of genetic engineering of crops and animals. I suspect that you could go back and look at the early days of almost any new technology and convincingly downplay its transformative potential.

Most new technologies ultimately fail to deliver. But the proper stance to take is to say that we just don’t know. What we do know is that there are many pressing and complex problems facing the future of agriculture. And, given that there is no compelling reason not to allow GM techniques to proceed, why take this tool out of the hands of scientists?

People care about GMOs because they symbolize corporate control of the food system, or unsustainable agriculture, or the basic unhealthiness of our modern diet. On the other side, people care about GMOs because they symbolize the victory of human ingenuity over hunger and suffering, or the triumph of market forces, or the wonder of science.

What is most disturbing about the GMO debate – and why it matters – is that the anti-GMO movement at almost every turn rejects empiricism as a means of understanding the world and making decisions about it. GMO opponents have largely rejected Johnson and his series.

They do not appear to believe that the kind of questions that Johnson asks – “Does insect resistant corn reduce the amount of insecticide used on farms?” – can even be asked. They already know the answer, and are completely unmoved by evidence.

The world faces so many challenges now, and we can only solve them if we believe that the world can be understood by studying it, that we can think up and generate possible solutions to the challenges we face, and that we can make rational decisions about which ones to use or not to use.

– See more at: http://www.michaeleisen.org/blog/?p=1530#sthash.GVFidZev.dpuf

Part 3.  Africa: Context is Crucial to Seeing Challenge of Hunger

October 17, 2013 / Des Moines Register
http://pulitzercenter.org/sites/default/files/styles/slideshow/public/10-16-13/farmerprocessingmilkintobutter640.jpg

Women farmers are processing more of their milk. Image by Sharon Schmickle. Tanzania, 2013.

To understand food security in sub-Saharan Africa, context is crucial. Some 500 million small farms feed 80 percent of the people who live in regions that are perilously close to hunger.
Published Oct 17, 2013  SHARON SCHMICKLE

Iowans who take in this year’s World Food Prize Borlaug Dialogue in Des Moines can gain a wealth of expert perspectives on the important challenge of nourishing a growing world population during the next century.
Learning the full measure of the challenge, though, calls for reaching beyond the lectures and panel discussions — reaching into the local reasons it has been so difficult to achieve global food security.
Context is crucial in a world where some 500 million small farms feed 80 percent of the people who live in regions that are perilously close to hunger.
To visit farms in those regions is to learn why it has been so difficult to stand up to the moral challenge the late Norman Borlaug delivered time and again, insisting that access to adequate food is a basic human right.
It is to meet female farmers like Sharifa Said Nambanga, who struggles to feed five children with the rice she can grow on a small plot in Zanzibar. Women do a hefty share of the farm work around the world. Often, though, they are shut off from the extension services that should deliver improved seeds, fertilizer and the know-how to use agriculture’s modern methods. Feeling abandoned, they limp along as best they can on their own.
It is to meet pastoralists like Parmelo Ndiimu. He is a Maasai elder who watches helplessly while the trees he needs to feed his goats are cut to make charcoal for cooking in urban kitchens. “If we won’t be able to feed our goats, we will not be able to feed our children,” Ndiimu said. “And we will be gone.”
It is to meet Tanzanian farmers who work their small plots throughout a full growing season only to see weevils destroy half their bean harvest. They know firsthand the tension between farmers and the ever evolving pests that attack crops in the field and after harvest.
It is to see corn planted from family seed wither in the field, stalks barren and green leaves giving way to limp yellow strips. Theoretically, the simple remedy should be improved seeds. But nothing is simple in the process of getting those improved seeds to small-scale farmers, especially when the improvement involved genetic modification of the plants.
In his later years, Borlaug addressed context in sub-Saharan Africa, recognizing that along with improved seed, farmers also needed to knock down barriers in their marketing, storage and processing systems. He challenged African leaders to invest more in agriculture.
Within that framework, it is clear that millions of small-scale farmers — especially those in Africa — operate amid tensions that limit their opportunities to extract more food from the technology that has filled porridge bowls and bread baskets elsewhere.

Part 4. Betting on the Impact of Synthetic Biology In Healthcare – By Jenny Rooke

Jenny Rooke drives innovation in the life sciences field through investing and business building around brilliant scientists and engineers with novel technologies. Prior, Jenny held multiple executive roles at U.S. Genomics.

I am an ardent believer in the potential of synthetic biology – its technologies, methods, and talented practitioners – to transform human life on just about every dimension: What we eat, how we make things, the character of our environment and how we move through it, how we are born, and, eventually, how long we live.

My more circumspect investor side is forced to admit that the evidence base of practical (not to mention profitable) applications of synthetic biology remains, shall we say, a work in progress. The first wave of synthetic biology companies that focused on energy/biofuels has been largely disappointing commercially, despite some notable technical successes, due in part to challenges related to scale-up, feedstock economics, and distribution.

It seems reasonable to search for proof cases of synthetic biology’s utility in human health; after all, the vast majority of biotechnology’s impact to date (practically and financially) has been in healthcare, including the creation of entirely novel categories of therapeutics and molecular diagnostics.

To be fair, it’s early yet to expect too many synthetic biology success stories in medicine. Synthetic biology as a field is just over a decade old and if it takes on average a decade for a new drug to move from the lab to the market, well, the math is obvious. In addition, there remain a great deal of technical, clinical, and safety risk inherent to applying synthetic biology technologies to human health problems (consider the painful lessons from the analogous field of gene therapy). This helps explain the reluctance of incumbent healthcare companies and traditional healthcare investors to make big bets on synthetic biology until the technology’s practical utility is more proven.

In 2011 and 2012, the Bill & Melinda Gates Foundation put out a call for grant applications to “Apply Synthetic Biology to Global Health Challenges” under its Global Health division, which aims to harness advances in science and technology to save lives in developing countries. The foundation’s Grand Challenges Explorations, or GCE, program is an ideal mechanism for fostering applications of synthetic biology.

Synthetic biology will play a critical role in enabling novel, affordable healthcare solutions for developing countries. Image source: GrandChallenges.org

For more information on the Grand Challenges in Global Health program, including a brief description of each project and a discussion of observed themes, see the review article “Synthetic biology as a source of global health innovation” (Syst Synth Biol (2013) 7:67–72).

Read Full Post »

Diagnostic Value of Cardiac Biomarkers


Diagnostic Value of Cardiac Biomarkers

Author and Curator: Larry H Bernstein, MD, FCAP 

These presentations covered several views of the utilization of cardiac markers that have evolved for over 60 years.  The first stage was the introduction of enzymatic assays and isoenzyme measurements to distinguish acute hepatitis and acute myocardial infarction, which included lactate dehydrogenase (LD isoenzymes 1, 2) at a time that late presentation of the patient in the emergency rooms were not uncommon, with the creatine kinase isoenzyme MB declining or disappeared from the circulation.  The world health organization (WHO) standard definition then was the presence of two of three:

1. Typical or atypical precordial pressure in the chest, usually with radiation to the left arm

2. Electrocardiographic changes of Q-wave, not previously seen, definitive; ST- elevation of acute myocardial injury with repolarization;
T-wave inversion.

3. The release into the circulation of myocardial derived enzymes –
creatine kinase – MB (which was adapted to measure infarct size), LD-1,
both of which were replaced with troponins T and I, which are part of the actomyosin contractile apparatus.

The research on infarct size elicited a major research goal for early diagnosis and reduction of infarct size, first with fibrinolysis of a ruptured plaque, and this proceeded into the full development of a rapidly evolving interventional cardiology as well as cardiothoracic surgery, in both cases, aimed at removal of plaque or replacement of vessel.  Surgery became more imperative for multivessel disease, even if only one vessel was severely affected.

So we have clinical history, physical examination, and emerging biomarkers playing a large role for more than half a century.  However, the role of biomarkers broadened.  Patients were treated with antiplatelet agents, and a hypercoagulable state coexisted with myocardial ischemic injury.  This made the management of the patient reliant on long term followup for Warfarin with the international normalized ratio (INR) for a standardized prothrombin time (PT), and reversal of the PT required transfusion with thawed fresh frozen plasma (FFP).  The partial thromboplastin test (PPT) was necessary in hospitalization to monitor the heparin effect.

Thus, we have identified the use of traditional cardiac biomarkers for:

1. Diagnosis
2. Therapeutic monitoring

The story is only the beginning.  Many patients who were atypical in presentation, or had cardiovascular ischemia without plaque rupture were problematic.  This led to a concerted effort to redesign the troponin assays for high sensitivity with the concern that the circulation should normally be free of a leaked structural marker of myocardial damage. But of course, there can be a slow leak or a decreased rate of removal of such protein from the circulation, and the best example of this would be the patient with significant renal insufficiency, as TnT is clear only through the kidney, and TNI is clear both by the kidney and by vascular endothelium.  The introduction of the high sensitivity assay has been met with considerable confusion, and highlights the complexity of diagnosis in heart disease.  Another test that is used for the diagnosis of heart failure is in the class of natriuretic peptides (BNP, pro NT-BNP, and ANP), the last of which has been under development.

While there is an exponential increase in the improvement of cardiac devices and discovery of pharmaceutical targets, the laboratory support for clinical management is not mature.  There are miRNAs that may prove valuable, matrix metalloprotein(s), and potential endothelial and blood cell surface markers, they require

1. codevelopment with new medications
2. standardization across the IVD industry
3. proficiency testing applied to all laboratories that provide testing
4. the measurement  on multitest automated analyzers with high capability in proteomic measurement  (MS, time of flight, MS-MS)

nejmra1216063_f1   Atherosclerotic Plaques Associated with Various Presentations               nejmra1216063_f2     Inflammatory Pathways Predisposing Coronary Arteries to Rupture and Thrombosis.        atherosclerosis progression

Read Full Post »


Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 11/15/2013

Relax, PCSK9ers: FDA won’t roadblock blockbusters from Sanofi, Amgen

By Damian Garde

On the heels of new guidelines casting doubts on a much-hyped new class of cholesterol drugs, the FDA said it would not demand long and costly outcomes trials before approving PCSK9 treatments from the likes of Amgen ($AMGN), Sanofi ($SNY) and Regeneron ($REGN), clearing the way for treatments expected to rake in up to $3 billion a year.

As Bloomberg reports, the FDA plans to stick to its guns in vetting cardiovascular drugs, looking at reductions in LDL cholesterol and blood pressure as surrogate endpoints for long-term health benefits. That’s a relief for the developers of PCSK9-targeting drugs, who have faced mounting uncertainty about what they’ll need to do to get their would-be blockbusters to market. Partners Sanofi and Regeneron lead the pack with the promising alirocumab, followed by Amgen, Pfizer ($PFE) and numerous others.

Earlier this week, the American College of Cardiology and the American Heart Association put out new guidelines for prescribing cholesterol treatments, recommending tried-and-true statins over more novel therapies because the old drugs’ down-the-line cardiovascular benefits are well-told. That stirred up long-running concerns that the FDA would toughen up its requirements for the coming crop of PCSK9 treatments, asking drug developers to dump millions into long-term studies that demonstrate hard outcomes

But while PCSK9 developers may not have to worry about new regulatory hurdles, what’s good enough for the FDA won’t necessarily sway payers, and the billion-dollar sales estimates tied to PCSK9 drugs are contingent on widespread adoption. With that in mind, Pfizer is plotting a massive, 22,000-patient outcomes trial, looking to demonstrate the PCSK9-targeting RN-316’s ability to improve cardiovascular health in the long run, a move that may spur its competitors to follow suit.

And the FDA’s conventional wisdom on cardiovascular endpoints may not stand pat. Eric Colman, a deputy director at CDER, told Bloomberg the agency is keeping a close eye on a post-market study of Merck’s ($MRK) Vytorin, and if the drug’s LDL-lowering ability doesn’t translate to lower rates of cardiovascular events, it may well rethink its requirements.

Related Articles:

AstraZeneca wins, Merck and AbbVie lose with new statin-use guidelines

Sanofi, Regeneron take the lead in blockbuster PhIII race of PCSK9 drugs

Pfizer bets big on PCSK9 with ‘massive’ Phase III outcomes study

 SOURCE

From: FierceBiotech <editors@fiercebiotech.com>
Reply-To: <editors@fiercebiotech.com>
Date: Fri, 15 Nov 2013 17:56:42 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>
Subject: | 11.15.13 | Sanofi, Amgen dodge PCSK9 hurdles

 

http://www.nature.com/news/genetics-a-gene-of-rare-effect-1.12773?goback=%2Egde_96118_member_230797138

Genetics: A Gene of Rare Effect

A mutation that gives people rock-bottom cholesterol levels has led geneticists to what could be the next blockbuster heart drug.

Stephen S. Hall

09 April 2013
ADAPTED FROM: PETER DAZELEY/GETTY

Indeed, Tracy’s well-being has been inspiring to doctors, geneticists and now pharmaceutical companies precisely because she is so normal. Using every tool in the modern diagnostic arsenal — from brain scans and kidney sonograms to 24-hour blood-pressure monitors and cognitive tests — researchers at the Texas medical centre have diagnostically sliced and diced Tracy to make sure that the two highly unusual genetic mutations she has carried for her entire life have produced nothing more startling than an incredibly low level of cholesterol in her blood. At a time when the target for low-density lipoprotein (LDL) cholesterol, more commonly called ‘bad cholesterol’, in Americans’ blood is less than 100 milligrams per decilitre (a level many people fail to achieve), Tracy’s level is just 14.

A compact woman with wide-eyed energy, Tracy (not her real name) is one of a handful of African Americans whose genetics have enabled scientists to uncover one of the most promising compounds for controlling cholesterol since the first statin drug was approved by the US Food and Drug Administration in 1987. Seven years ago, researchers Helen Hobbs and Jonathan Cohen at UT-Southwestern reported1 that Tracy had inherited two mutations, one from her father and the other from her mother, in a gene called PCSK9, effectively eliminating a protein in the blood that has a fundamental role in controlling the levels of LDL cholesterol. African Americans with similar mutations have a nearly 90% reduced risk of heart disease. “She’s our girl, our main girl,” says Barbara Gilbert, a nurse who has drawn some 8,000 blood samples as part of Cohen and Hobbs’ project to find genes important to cholesterol metabolism.

Of all the intriguing DNA sequences spat out by the Human Genome Project and its ancillary studies, perhaps none is a more promising candidate to have a rapid, large-scale impact on human health than PCSK9. Elias Zerhouni, former director of the US National Institutes of Health (NIH) in Bethesda, Maryland, calls PCSK9 an “iconic example” of translational medicine in the genomics era. Preliminary clinical trials have already shown that drugs that inhibit the PCSK9 protein — used with or without statins — produce dramatic reductions in LDL cholesterol (more than 70% in some patients). Half-a-dozen pharmaceutical companies — all aiming for a share of the global market for cholesterol-reducing drugs that could reach US$25 billion in the next five years according to some estimates — are racing to the market with drugs that mimic the effect of Tracy’s paired mutations.

Free interview

Stephen Hall talks about Sharlayne’s unusual condition and whether similar cases might lead to a new line of drugs.

Zerhouni, now an in-house champion of this class of drug as an executive at drug firm Sanofi, headquartered in Paris, calls the discovery and development of PCSK9 a “beautiful story” in which researchers combined detailed physical information about patients with shrewd genetics to identify a medically important gene that has made “super-fast” progress to the clinic. “Once you have it, boy, everything just lines up,” he says. And although the end of the PCSK9 story has yet to be written — the advanced clinical trials now under way could still be derailed by unexpected side effects — it holds a valuable lesson for genomic research. The key discovery about PCSK9‘s medical potential was made by researchers working not only apart from the prevailing scientific strategy of genome research over the past decade, but with an almost entirely different approach.

As for Tracy, who lives in the southern part of Dallas County, the implications of her special genetic status have become clear. “I really didn’t understand at first,” she admits. “But now I’m watching ads on TV [for cholesterol-lowering drugs], and it’s like, ‘Wow, I don’t have that problem’.”

A heart problem

Cardiovascular disease is — and will be for the foreseeable future, according to the World Health Organization — the leading cause of death in the world, and its development is intimately linked to elevated levels of cholesterol in the blood. Since their introduction, statin drugs have been widely used to lower cholesterol levels. But Jan Breslow, a physician and geneticist at Rockefeller University in New York, points out that up to 20% of patients cannot tolerate statins’ side effects, which include muscle pain and even forgetfulness. And in many others, the drugs simply don’t control cholesterol levels well enough.

The search for better treatments for heart disease gained fresh impetus after scientists published the draft sequence of the human genome in 2001. In an effort to identify the genetic basis of common ailments such as heart disease and diabetes, geneticists settled on a strategy based on the ‘common variant hypothesis’. The idea was that a handful of disease-related versions (or variants) of genes for each disease would be common enough — at a frequency of roughly 5% or so — to be detected by powerful analyses of the whole genome. Massive surveys known as genome-wide association studies compared the genomes of thousands of people with heart disease, for example, with those of healthy controls. By 2009, however, many scientists were lamenting the fact that although the strategy had identified many common variants, each made only a small contribution to the disease. The results for cardiovascular disease have been “pretty disappointing”, says Daniel Steinberg, a lipoprotein expert at the University of California, San Diego.

Single-minded: Helen Hobbs and Jonathan Cohen’s approach to heart-disease genetics yielded a target for drugs that could compete with statins.MISTY KEASLER/REDUX/EYEVINE

More than a decade earlier, in Texas, Hobbs and Cohen had taken the opposite tack. They had backgrounds in Mendelian, or single-gene, disorders, in which an extremely rare variant can have a big — often fatal — effect. They also knew that people with a particular Mendelian disorder didn’t share a single common mutation in the affected gene, but rather had a lot of different, rare mutations. They hypothesized that in complex disorders, many different rare variants were also likely to have a big effect, whereas common variants would have relatively minor effects (otherwise natural selection would have weeded them out). “Jonathan and I did not see any reason why it couldn’t be that rare variants cumulatively contribute to disease,” Hobbs says. To find these rare variants, the pair needed to compile detailed physiological profiles, or phenotypes, of a large general population. Cohen spoke of the need to “Mendelize” people — to compartmentalize them by physiological traits, such as extremely high or low cholesterol levels, and then look in the extreme groups for variations in candidate genes known to be related to the trait.

The pair make a scientific odd couple. Hobbs, who trained as an MD, is gregarious, voluble and driven. Cohen, a soft-spoken geneticist from South Africa, has a laid-back, droll manner and a knack for quantitative thinking. In 1999, they set out to design a population-based study that focused on physical measurements related to heart disease. Organized with Ronald Victor, an expert on high blood pressure also at UT Southwestern, and funded by the Donald W. Reynolds Foundation in Las Vegas, Nevada, the Dallas Heart Study assembled exquisitely detailed physiological profiles on a population of roughly 3,500 Dallas residents2. Crucially, around half of the participants in the study were African Americans, because the researchers wanted to probe racial differences in heart disease and high blood pressure. The team measured blood pressure, body mass index, heart physiology and body-fat distribution, along with a battery of blood factors related to cholesterol metabolism — triglycerides, high-density lipoprotein (HDL) cholesterol and LDL cholesterol. In the samples of blood, of course, they also had DNA from each and every participant.

As soon as the database was completed in 2002, Hobbs and Cohen tested their rare-variant theory by looking at levels of HDL cholesterol. They identified the people with the highest (95th percentile) and lowest (5th percentile) levels, and then sequenced the DNA of three genes known to be key to metabolism of HDL cholesterol. What they found, both in Dallas and in an independent population of Canadians, was that the number of mutations was five times higher in the low HDL group than in the high group3. This made sense, Cohen says, because most human mutations interfere with the function of genes, which would lead to the low HDL numbers. Published in 2004, the results confirmed that rare, medically important mutations could be found in a population subdivided into extreme phenotypes.

Armed with their extensive database of cardiovascular traits, Hobbs and Cohen could now dive back into the Dallas Heart Study whenever they had a new hypothesis about heart disease and, as Cohen put it, “interrogate the DNA”. It wasn’t long before they had an especially intriguing piece of DNA at which to look.

The missing link

In February 2003, Nabil Seidah, a biochemist at the Clinical Research Institute of Montreal in Canada, and his colleagues reported the discovery of an enigmatic protein4. Seidah had been working on a class of enzymes known collectively as proprotein convertases, and the researchers had identified what looked like a new member of the family, called NARC-1: neural apoptosis-regulated convertase 1.

“We didn’t know what it was doing, of course,” Seidah says. But the group established that the gene coding the enzyme showed activity in the liver, kidney and intestines as well as in the developing brain. The team also knew that in humans the gene mapped to a precise genetic neighbourhood on the short arm of chromosome 1.

That last bit of geographical information pointed Seidah to a group led by Catherine Boileau at the Necker Hospital in Paris. Her team had been following families with a genetic form of extremely high levels of LDL cholesterol known as familial hypercholesterolaemia, which leads to severe coronary artery disease and, often, premature death. Group member Marianne Abifadel had spent five fruitless years searching a region on the short arm of chromosome 1 for a gene linked to the condition. When Seidah contacted Boileau and told her that he thought NARC-1 might be the gene she was looking for, she told him, “You’re crazy”, Seidah recalls. Seidah bet her a bottle of champagne that he was correct; within two weeks, Boileau called back, saying: “I owe you three bottles.”

“The PCSK9 story is a terrific example of an up-and-coming pattern of translational research.”

In 2003, the Paris and Montreal groups reported that the French families with hypercholesterolaemia had one of two mutations in this newly discovered gene, and speculated that this might cause increased production of the enzyme5. Despite Seidah’s protests, the journal editors gave both the gene and its protein product a new name that fit with standard nomenclature: proprotein convertase subtilisin/kexin type 9, or PCSK9. At around the same time, Kara Maxwell in Breslow’s group at Rockefeller University6 and Jay Horton, a gastroenterologist at UT-Southwestern7 also independently identified the PCSK9 gene in mice and revealed its role in a previously unknown pathway regulating cholesterol8.

The dramatic phenotype of the French families told Hobbs that “this is an important gene”. She also realized that in genetics, mutations that knock out a function are much more common than ones that amplify function, as seemed to be the case with the French families. “So immediately I’m thinking, a loss-of-function mutation should manifest as a low LDL level,” she says. “Let’s go and see if that’s true.”

Going to extremes

Hobbs and Cohen had no further to look than in the extreme margins of people in the Dallas Heart Study. In quick order, they identified the highest and lowest LDL readings in four groups: black women, black men, white women and white men. They then resequenced the PCSK9 gene in the low-cholesterol groups, looking for mutations that changed the make-up of the protein.

They found seven African Americans with one of two distinct ‘nonsense’ mutations in PCSK9 — mutations that essentially aborted production of the protein. Then they went back and looked for the same mutations in the entire population. Just 2% of all black people in the Dallas study had either of the two PCSK9 mutations — and those mutations were each associated with a 40% reduction of LDL cholesterol in the blood9. (The team later detected a ‘missense mutation’ in 3% of white people, which impaired but did not entirely block production of the protein.) The frequency of the mutations was so low, Hobbs says, that they would never have shown up in a search for common variants.

When Hobbs and Cohen published their findings in 2005, they suggested that PCSK9 played a crucial part in regulating bad cholesterol, but said nothing about whether the mutations had any effect on heart disease. That evidence came later that year, when they teamed up with Eric Boerwinkle, a geneticist at the University of Texas Health Science Center in Houston, to look forPCSK9 mutations in the Atherosclerosis Risk in Communities (ARIC) study, a large prospective study of heart disease that had been running since 1987. To experts such as Steinberg, the results10 — published in early 2006 — were “mind-blowing”. African Americans in ARIC who had mutations in PCSK9 had 28% less LDL cholesterol and an 88% lower risk of developing heart disease than people without the mutations. White people with the less severe mutation in the gene had a 15% reduction in LDL and a 47% reduced risk of heart disease.

How did the gene exert such profound effects on LDL cholesterol levels? As researchers went on to determine11, the PCSK9 protein normally circulates in the bloodstream and binds to the LDL receptor, a protein on the surface of liver cells that captures LDL cholesterol and removes it from the blood. After binding with the receptor, PCSK9 escorts it into the interior of the cell, where it is eventually degraded. When there is a lot of PCSK9 (as in the French families), there are fewer LDL receptors remaining to trap and remove bad cholesterol from the blood. When there is little or no PCSK9 (as in the black people with mutations), there are more free LDL receptors, which in turn remove more LDL cholesterol.

“We didn’t understand why everybody wasn’t doing what we were doing.”

The UT-Southwestern group, meanwhile, went back into the community looking for family members who might carry additional PCSK9 mutations. In September 2004, Gilbert, the nurse known as ‘the cholesterol lady’ in south Dallas because of her frequent visits, knocked on the door of Sharlayne Tracy’s mother, an original member of the Dallas Heart Study. Gilbert tested Tracy, as well as her sister, brother and father. “They tested all of us, and I was the lowest,” Tracy says. Zahid Ahmad, a doctor working with Hobbs at UT-Southwestern, was one of the first to look at Tracy’s lab results. “Dr Zahid was in awe,” Tracy recalled. “He said, ‘You’re not supposed to be so healthy!’.”

It wasn’t just that her LDL cholesterol measured 14. As a person with two dysfunctional copies of the gene — including a new type of mutation — Tracy was effectively a human version of a knockout mouse. The gene had been functionally erased from her genome, and PCSK9 was undetectable in her blood without any obvious untoward effects. The genomics community might have been a little slow to understand the significance, Hobbs says, “but the pharmaceutical companies got it right away”.

The next statin?

This being biology, however, the road to the clinic was not completely smooth. The particular biology of PCSK9 has so far thwarted efforts to find a small molecule that would interrupt its interaction with the LDL receptor and that could be packaged in a pill. But the fact that the molecule operates outside cells means that it is vulnerable to attack by monoclonal antibodies — one of the most successful (albeit most expensive) forms of biological medicine.

The results of early clinical trials have caused a stir. Regeneron Pharmaceuticals of Tarrytown, New York, collaborating with Sanofi, published phase II clinical-trial results12 last October showing that patients with high LDL cholesterol levels who had injections every two weeks of an anti-PCSK9 monoclonal antibody paired with a high-dose statin saw their LDL cholesterol levels fall by 73%; by comparison, patients taking high-dose statins alone had a decrease of just 17%. Last November, Regeneron and Sanofi began to recruit 18,000 patients for phase III trials that will test the ability of their therapy to cut cardiovascular events, including heart attacks and stroke. Amgen of Thousand Oaks, California, has also launched several phase III trials of its own monoclonal antibody after it reported similarly promising results13. Among other companies working on PCSK9-based therapies are Pfizer headquartered in New York, Roche based in Basel, Switzerland, and Alnylam Pharmaceuticals of Cambridge, Massachusetts. (Hobbs previously consulted for Regeneron and Pfizer, and now sits on the corporate board of Pfizer.)

Not everyone is convinced that a huge market awaits this class of cholesterol-lowering drugs. Tony Butler, a financial analyst at Barclays Capital in New York, acknowledges the “beautiful biology” of the PCSK9 story, but wonders if the expense of monoclonal drugs — and a natural reluctance of both patients and doctors to use injectable medicines — will constrain potential sales. “I have no idea what the size of the market may be,” he says.

“Everything hinges on the phase III side effects,” says Steinberg. So far, the main side effects reported have been minor, such as reactions at the injection site, diarrhoea and headaches. But animal experiments have raised potential red flags: the Montreal lab reported in 2006 that knocking out the gene in zebrafish is lethal to embryos14. That is why the case of Tracy was “very, very helpful” to drug companies, says Hobbs. Although her twin mutations have essentially deprived her of PCSK9 throughout her life, doctors have found nothing abnormal about her.

That last point may revive a debate in the cardiology community: should drug therapy to lower cholesterol levels, including statins and the anti-PCSK9 medicines, if they pan out, be started much earlier in patients than their 40s or 50s? That was the message Steinberg took from the people withPCSK9 mutations in the ARIC study — once he got over his shock at the remarkable health effects. “My first reaction was, ‘This must be wrong. How could that be?’And then it hit me — these people had low LDL from the day they were born, and that makes all the difference.” Steinberg argues that cardiologists “should get off our bums” and reach a consensus about beginning people on cholesterol-lowering therapy in their early thirties. But Breslow, a former president of the American Heart Association, cautions against being too aggressive too soon. “Let’s start out with the high-risk individuals and see how they do,” he says.

Not long after Hobbs and Cohen published their paper in 2006, they began to get invited to give keynote talks at major cardiology meetings. Soon after, the genetics community began to acknowledge the strength of their approach. In autumn 2007, then-NIH director Zerhouni organized a discussion at the annual meeting of the institutes’ directors to raise the profile of the rare-variant approach and contrast it with genome-wide studies. “Obviously, the two approaches are opposed to each other, and the question was, what was the relative value of each?” says Zerhouni. “I thought the PCSK9 story was a terrific example of an up-and-coming pattern of translational research” — indeed, he adds, “a harbinger of things to come”.

Hobbs and Cohen might not have found their gene if they had not had a hunch about where to look, but improved sequencing technology and decreasing costs now allow genomicists to incorporate the rare variant approach and to mount large-scale sweeps in search of such variants. “Gene sequencing is getting cheap enough that if there’s another gene like PCSK9 out there, you could probably find it genome-wide,” says Jonathan Pritchard, a population biologist at the University of Chicago, Illinois.

“What was amazing to us,” says Hobbs, “was that the genome project was spending all this time, energy, effort sequencing people, and they weren’t phenotyped, so there was no potential for discovery. We didn’t understand, and couldn’t understand, why everybody wasn’t doing what we were doing. Particularly when we started making discoveries.”

SOURCE:

Nature 496, 152–155 (11 April 2013) doi:10.1038/496152a

References
  1. Zhao, Z. et al. Am. J. Hum. Genet. 79, 514–523 (2006).

    Show context

  2. Victor, R. G. et al. Am. J. Cardiol. 93, 1473–1480 (2004).

    Show context

  3. Cohen, J. C. et al. Science 305, 869–872 (2004).

    Show context

  4. Seidah, N. G. et al. Proc. Natl Acad. Sci. USA 100, 928–933 (2003).

    Show context

  5. Abifadel, M. et al. Nature Genet. 34, 154–156 (2003).

    Show context

  6. Maxwell, K. N., Soccio, R. E., Duncan, E. M., Sehayek, E. & Breslow, J. L. J. Lipid Res. 44,2109–2119 (2003).

    Show context

  7. Horton, J. D. et al. Proc. Natl Acad. Sci. USA 100, 12027–12032 (2003).

    Show context

  8. Maxwell, K. N. & Breslow, J. L. Proc. Natl Acad. Sci. USA 101, 7100–7105 (2004).

    Show context

  9. Cohen, J. et al. Nature Genet. 37, 161–165 (2005).

    Show context

  10. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. N. Engl. J. Med. 354, 1264–1272(2006).

    Show context

  11. Horton, J. D., Cohen, J. C. & Hobbs, H. H. J. Lipid Res. 50, S172–S177 (2009).

    Show context

  12. Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G. & Stein, E. A. N. Engl. J. Med. 367,1891–1900 (2012).

    Show context

  13. Koren, M. J. et al. Lancet 380, 1995–2006 (2012).

    Show context

  14. Poirier, S. et al. J. Neurochem. 98, 838–850 (2006).

    Show context

Author information

Affiliations

  1. Stephen S. Hall is a science writer in New York who also teaches public communication to graduate students in science at New York University.

Read Full Post »


Reporters: Aviva Lev-Ari, PhD, RN and Pnina Abir-Am, PhD
Jeffrey L. Sturchio

Senior Partner, Rabin Martin

Jeffrey L. Sturchio is senior partner at Rabin Martin, a global health strategy firm in New York. Prior to joining the firm, he served as president and CEO of the Global Health Council. Before joining the Council, Dr. Sturchio was vice president of Corporate Responsibility at Merck & Co. Inc., president of the Merck Company Foundation and chairman of the U. S. Corporate Council on Africa, whose 150 member companies represent some 85 percent of total US private sector investment in Africa. He is a visiting scholar at the Institute for Applied Economics and the Study of Business Enterprise at Johns Hopkins University, a Fellow of the American Association for the Advancement of Science and a member of the Council on Foreign Relations. He received an AB in history from Princeton University and a PhD in the history and sociology of science from the University of Pennsylvania.

World Cancer Day: Treatment Should Not Be a Luxury
Posted: 02/04/2013 10:20 am
Huffington Post IMPACT
Author: Jeffrey L. Sturchio, Senior Partner, Rabin Martin

co-authored by Cary Adams.

All of us have been touched by cancer, whether personally or through the experience of our families and friends. For those of us living in the developed world, many types of cancer have ceased to be the “dread disease” they once were: Given the remarkable advances in basic science and oncology, it’s more a question of what the best course of treatment is, rather than one of availability or affordability. But for most of the world, access to cancer screening, detection, diagnosis and oncology care is still an unattainable luxury. Considering that nearly half of cancer cases — and 55 percent of the deaths — occur in less developed countries, we need to make progress now.

If left unchecked, the annual economic burden of cancer will be an estimated $458 billion by 2030, according to a study by the World Economic Forum and Harvard School of Public Health. But the human cost of 21.4 million new cases per year by 2030 is, quite simply, unacceptable. In commemoration of World Cancer Day (Today, February 4), we call for the global community to step-up its efforts to address cancer and other NCDs.

Cancers, along with other non-communicable diseases (NCDs) such as diabetes, upper respiratory infections and cardiovascular disease, are the leading causes of mortality around the world. Indeed, the number of cancer deaths alone surpasses those attributed to AIDS, tuberculosis and malaria combined. Once considered illnesses of the wealthy, 80 percent of the estimated 36 million NCD-related deaths actually occur in low- to middle- income countries, according to the World Health Organization. And while a global movement for action on NCDs has been gathering momentum in recent years, much remains to be done.

The Institute for Applied Economics, Global Health and the Study of Business Enterprise at Johns Hopkins University recently released a set of policy briefs that present recommendations for Addressing the Gaps in Global Policy and Research for Non-Communicable Disease. The publication compiles the findings of a Working Group of leading experts in the field and offers a road map of actionable recommendations for reducing the global burden of these diseases.

The report echoes many of the themes put forth by the global cancer community for achieving the goals articulated in the World Cancer Declaration. For starters, there needs to be a multi-sectoral approach to cancer. Governments, civil society, academe and the private sector must work together to leverage strengths and efficiencies to advance efforts to reduce the burden of cancer.

Greater participation by the private sector in a transparent and open way will improve efforts against the disease in coming years. Certainly, private-public partnerships to tackle cancer exist, but greater collaboration among stakeholders is needed. One suggestion may be to develop a knowledge exchange network for oncology researchers in industry and academe to accelerate the rate of progress in discovering and developing new vaccines, personalized medicines, pharmaceuticals and other essential medical technologies. While their most significant role is — and will continue to be — in R&D, the private sector can also lend considerable expertise in systems efficiencies, human resource development and supply chain management, to name just a few areas in which their capabilities can improve the global response to cancer.

Governments need to play a more active role in actively reducing and raising awareness about risk factors for cancer and other NCDs. They need to work with civil society and industry to reduce tobacco and excessive alcohol use, while promoting healthier diets and physical activity at the national and community levels. Again the private sector can play a lead role in improving the health impacts of their products to reduce the global growth in NCDs.

Countries need to make greater investments in building the capacity of local health workers so they are more capable of educating patients about reducing their cancer risk through behavior modification as well as immunization against human papilloma virus (HPV) and hepatitis B (HBV) infections (which can lead to cervical cancer and primary liver cancer, respectively). Health workers are the first line of defense, detecting hallmarks of disease and providing cancer screening, treatment and, when necessary, long-term care. Moreover, countries need to re-evaluate how they can retain health workers who are trained in cancer care. Without them, all interventions become impossible.

Finally, there needs to be greater focus on providing equitable access to screening, early diagnosis and treatment. Self-exams and visual inspection with acetic acid for breast cancer and cervical cancer screening respectively, are two excellent examples of effective, inexpensive, life-saving innovations that can be implemented even in low-resource settings. Integrating these methods into existing primary, reproductive and maternal health service models would help reduce the 750,000 deaths from cervical and breast cancer each year.

It’s a lot of work, but for many of us, cancer hits very close to home. By working together to combat cancer, each doing our part, we can begin to make a difference in the lives of millions — making cancer care and treatment not a luxury, but a reality.

Cary Adams is CEO of the Union for International Cancer Control (UICC), which helps the global health community accelerate the fight against cancer. Its growing membership of over 700 organisations in 155 countries features the world’s major cancer societies, ministries of health and patient groups and includes influential policy makers, researchers and experts in cancer prevention and control. Adams and his team focus on global advocacy to deliver the World Cancer Declaration targets by 2020, running global programs that address key cancer issues and use their membership reach to bring about the exchange of best practice globally. He recently became Chair of the NCD Alliance, a coalition of around 2,000 NGOs working on non-communicable diseases.

 SOURCE:
Jeffrey L. Sturchio
Doug Ulman

The Global Burden of Cancer

Posted: 02/04/2011 11:44 am
Most of us in developed countries have dwelled in the shadow of cancer. We’ve anxiously awaited a test result, become intimate with chemotherapy for ourselves or a loved one or held vigil at a bedside.

During those intense and often tragic periods, we usually have options — education, treatment, pain relief and sometimes, blessedly, remission and recovery — that is, if we happen to reside in a wealthy country. Not so for millions of others, adults and children alike, in poorer countries where more than 70 percent of all cancer deaths occur yet five percent or less of cancer resources are allocated to the people living there, despite the growing cancer burden.

Cancer is a growing cause of death worldwide. The cancer burden in low- and middle-income countries is increasingly disproportionate. Globally in 2009, there were an estimated 12.9 million cases of cancer, a number expected to double by 2020, with 60 percent of new cases occurring in low- and middle-income countries.

Not only do these countries carry more than half the disease burden, they lack the resources for cancer awareness and prevention, early detection, treatment or palliative options to relieve the staggering pain and human suffering if the disease is untreated — an unthinkable outcome for people who have cancer in rich nations.

Cancer also has the most devastating economic impact of any cause of death in the world, according to the recent landmark report, “The Global Economic Cost of Cancer,” released by the American Cancer Society and Livestrong. Premature deaths and disability from cancer cost the global economy nearly 1 trillion dollars a year. The data from this study provides compelling evidence that balancing the world’s global health agenda to address cancer more effectively will save not only millions of lives, but also billions of dollars.

By making cancer a global priority, as with many other non-communicable diseases, cancer deaths can be prevented an estimated 40 percent or more. This goal is a particular focus of this year’s World Cancer Day(today, February 4). But prevention can only be achieved through investments in awareness and education. Neglect of prevention leads to unaffordable treatment.

Even though tobacco use is the most preventable cause of cancer, lung cancer still kills more people worldwide than any other — a trend likely to surge unless efforts for global tobacco control are greatly accelerated. Tobacco use is responsible for 1.8 million cancer deaths per year, 60 percent in low- and middle-income nations, thanks to the tobacco industry’s unrelenting country-by-country approach to marketing their addictive product, including to youth. Last year, the Australian Broadcasting Corporation won a Global Health Council Excellence in Media Award for its hard-hitting and poignant exposé of tobacco marketing in Indonesia, “80 Million a Day: Big Tobacco’s New Frontier.” We need to cast more light on this invisible killer.

Other preventable risk factors for all cancers are unhealthy lifestyles (including alcohol abuse, inadequate diet and physical inactivity), exposure to occupational (e.g., asbestos) or environmental carcinogens (e.g., indoor air pollution), radiation (e.g., ultraviolet and ionizing radiation) and infections.

Cancers due to infectious diseases account for 8-10 percent of cases in high income countries, but 20-26 percent in developing countries. The human-to-human spread of viruses and bacteria can lead to liver and stomach cancers, lymphomas and leukemia. In addition to infections, many reproductive health diseases are linked to cancer. Strengthening the health systems of developing countries will pave the way for improved vaccine delivery and wider coverage of immunizations that will save lives and protect people’s health.

The Global Health Council and Livestrong call on global partners, allies, donors, policymakers, communities and individuals to work collaboratively to address the treatment expenditure gap and change the trajectory of this tidal wave of cancer. We have a choice – invest now or pay later with significant government spending and the loss of millions of lives and lessened productivity.

Capacity building is essential. Ministries of health, education and finance need to be engaged in developing and supporting plans that include both training of personnel to diagnose and treat cancer patients and strategies to reduce costs and strengthen health systems.

We need to focus on cancer surveillance to set standards to understand better the burden of cancer and the impacts of interventions. We need to implement relevant interventions at scale, including those that draw on successful models that address other diseases. We must rapidly expand information and awareness campaigns on a global scale to reach deeply into affected communities of developing countries. And we need continued investments in research and development for improved knowledge of the science of cancer and better drugs, vaccines and new tools for cancer prevention and control.

Starting today, advocates, governments, non-profits and the private sector must drive new and effective policies, programs and investments. Patients and survivors around the world cannot wait a moment longer for us to advance the global fight against cancer. Failing to act is indefensible — the human and economic costs are too high.

See more information at “Cancer in Developing Countries,” Global Health Council.

 SOURCE:

Around the globe, from Cape Town to Kathmandu, from Manila to Mexico City, millions will be celebrating the 100th anniversary of International Women’s Day on March 8 — a day to honor the achievements made by and for women. Looking at this milestone through a global health lens, we see an increasingly positive picture, but the view is far from perfect. In fact, we stand at a crossroads.

Globally, we’ve seen a notable decline in maternal deaths from half a million women to 342,000 annually. This is still far too many, but it is an important step in the right direction. Yet this progress is at risk, with mounting efforts underway to deny access to one of the best investments in women’s health: family planning.

In Bangladesh, just last month, a national survey showed a 40 percent drop in maternal deaths during the last decade. One of the contributing factors? Family planning. That is an unprecedented step forward.

Tanzania achieved a 21.5 percent drop in maternal deaths during the last five years, precipitated in part by increased access to and enthusiastic use of modern contraception. Another step forward.

In places like Ghana and Ethiopia, women every day have access to more contraceptive options — another step forward — as they endeavor to plan their families and define their futures. Women like Ayera Kabele, an ambitious 30-year old in Addis Ababa. She married in her early 20s and had a child soon thereafter. But she was also a student who wanted to finish college — a dream achieved because she was able to delay having another child by using an IUD. Four years later, degree in hand, Ayera and her husband were ready for their second child — another dream achieved. Yet another step forward.

This scenario between couples plays out every day around the world — including here in the United States. These are universal conversations about when to start a family and how many children to have. Anyone who has been a party to one can appreciate how vital they are to the health and well-being not only of women, but also of their families as well.

Why is that? In addition to saving women from death and injury during pregnancy or childbirth, saving mothers’ lives saves babies’ lives. Family planning also boosts women’s economic empowerment and creates an environment where children have a better chance not only to survive, but also to thrive. Strong and healthy families lead to stronger and more stable communities, in a virtuous cycle toward prosperity for nations.

We know that up to one-third of maternal deaths could be prevented if every woman who wanted to use contraception to limit or space her births was able to do so. In part, this is due to fewer unwanted pregnancies — especially when women have no other options — and thus to fewer women seeking abortion to end them. Mostly, though, it’s because every pregnancy and childbirth poses risks, especially where medical care is inadequate, if it exists at all. This is how family planning saves lives — and more.

Yet flying in the face of mounting evidence, there is a real risk that the United States foreign assistance budget will include drastic cuts to international family planning — the catalyst to so much good in countless communities worldwide. Indeed, at a moment when every budget dollar must be used as efficiently and effectively as possible, few investments pay better long-term dividends than family planning.

Just four years remain until the deadline for achieving the Millennium Development Goals (MDGs) set by the United Nations. A report released last year rated access to reproductive health care as low or moderate in 70 percent of the regions surveyed. This is not acceptable.

There have been strong policy and funding commitments made in the United States’ Global Health Initiative as well as at the United Nations (U.N.) to bolster access to and support for family planning as vital investments to improve the lives of women and families worldwide. The year 2010 also saw the launch of the first-ever U.N.’s Global Strategy for Women’s and Children’s Health and ongoing efforts by the State Department’s Office on Global Women’s Issues to link foreign policy with women’s rights. There is much reason for optimism.

As we mark the centennial of International Women’s Day, supporters of women’s health worldwide must continue to advocate for family planning and reproductive health services, which have done so much for women and girls in the U.S. and in so many countries around the world.

See the Global Health Council position paper on Maternal, Newborn, Child and Reproductive Health.

 Follow Jeffrey L. Sturchio on Twitter: www.twitter.com/globalhealthorg
SOURCE:

Read Full Post »


Reporter: Aviva Lev-Ari, PhD, RN

 

Gates Foundation funds research to improve health in developing countries
Lauren Braun as a volunteer in Peru

Division of Nutritional Sciences
As a volunteer in the summer of 2008, Lauren Braun ’11 fills a prescription in a makeshift rural pharmacy in Peru.
Alma Sana bracelets

Provided/Alma Sana
Alma Sana bracelets use symbols to avoid language barriers.

A Cornell plant virologist, an alumna and three Weill Cornell Medical College researchers have each received grants from the Bill & Melinda Gates Foundation‘s Grand Challenges in Global Health initiative.

One grant awarded to Jeremy Thompson in the Department of Plant Pathology and Plant-Microbe Biology will fund a project that takes advantage of new technology to rapidly determine the structure of RNA in viruses, which may lead to a new method for developing virus-resistant plants. Thompson, a research associate in the lab of Keith Perry, associate professor of plant pathology, will work with Perry to uncover new targets for plant virus resistance and with Julius Lucks, assistant professor of chemical and biomolecular engineering, who has developed new RNA structure mapping technology.

Viruses are known to use their RNA to hijack the replication machinery in host cells to make more copies of the virus. The researchers hope that determining the RNA structure will reveal plant proteins that are involved in viral replication.

“We want to try and map the structure of viral RNA, map the way it folds, and then we can potentially identify host proteins that are involved in virus replication and function,” said Thompson.

Once these plant proteins are identified, the researchers will look for genes that code for those proteins and try to alter their expression within the plant. “If we can affect the amount of protein involved, we can potentially hinder virus replication,” Thompson added. Using refined engineering methods to knock out or silence such protein-coding genes, the researchers may then create lines of virus-resistant plants.

The researchers will begin by examining viruses and host proteins in bean, tobacco and arabidopsis; bean, because of its importance as a staple in developing countries and the latter two because their genomes have been fully sequenced.

The one-and-a-half year, $100,000 grant represents a first phase that, if successful, allows the team to become eligible for phase two and an additional $1 million.

Lauren Braun

Braun

As the main objective of the Gates Foundation Grand Challenges in Global Health initiative is to improve the quality of life in developing countries, this project aims to “improve resistance against particular diseases for small-holder farmers, with all intellectual property being open to developing countries,” Thompson said. Plant viruses lead to billions of dollars in agricultural production losses each year.

Lauren Braun ’11 received a $100,000 grant to field-test in Peru a simple, inexpensive immunization-tracking bracelet for babies. Braun conceived the idea after spending the summer of 2008 as a volunteer at two rural health clinics in Peru, and she presented it on campus in the Entrepreneurship@Cornell’s 2011 Big Idea Competition.

The World Health Organization estimates that globally 1.5 million children die of vaccine-preventable diseases each year, and one in five children will die from such a disease before age 5.

Braun formed the nonprofit Alma Sana Inc. (Spanish for healthy soul) to manufacture and distribute the bracelets, which bypass language barriers and illiteracy by using symbols to show mothers the vaccinations their children need and numbers to show when they are due. The bracelet is to be worn by a child from birth to age 4, with the goal that more children will live to age 5.

A paper reminder system failed, Braun reports, because children are not brought in for their vaccinations and stored vaccine spoils and must be discarded, increasing costs. The bracelet also tells public health workers which vaccination each child needs.

The Gates Foundation initiative seeks new approaches to optimize immunization systems. In 2010, they said, a quarter of a million doses of pentavalent vaccine, costing nearly $1 million, expired in one country’s central store because the system charged with delivering them was not ready to manage it.

Three researchers at Weill Cornell Medical College have received Gates Foundation grants totaling $1.5 million from the Grand Challenges initiative for innovative research aimed at fighting HIV and tuberculosis.

SOURCE:

 

Read Full Post »