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Pathophysiological Effects of Diabetes on Ischemic-Cardiovascular Disease and on Chronic Obstructive Pulmonary Disease (COPD)

Posted in Atherogenic Processes & Pathology, Best evidence, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cardiovascular Research, Curation, Curation methodology, Diabetes Mellitus, Discovery process, Evidence-based decision-making, Evolutionary cognition, Experimental validation, Explanatory, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Human Immune System in Health and in Disease, Indigent Nutrition, Innovation in Immunology Diagnostics, International Global Work in Pharmaceutical, Interviews with Scientific Leaders, Medicare and Medicaid, Metabolomics, Nephrology, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, Systemic Inflammatory Response Related Disorders, Theoretic convergence, Translational Effectiveness, Translational Research, Translational Science, Uninsured and Underinsured, tagged AMI, Arterial stiffness, comorbidities - type 2 DM, COPD, coronary vascular disease, Diabetes management, Diabetes mellitus type 2, hs-CPR, Nutrition and Metabolism Disorders, Nutritional Supplements, prediabetes, proinflammatory, statins, waist circumference on January 15, 2014| Leave a Comment »

Pathophysiological Effects of Diabetes on Ischemic-Cardiovascular Disease and on Chronic Obstructive Pulmonary Disease (COPD)

Curator:  Larry H. Bernstein, MD, FCAP

Article ID #106: Pathophysiological Effects of Diabetes on Ischemic-Cardiovascular Disease and on Chronic Obstructive Pulmonary Disease (COPD). Published 1/15/2014

WordCloud Image Produced by Adam Tubman

This is a multipart article that develops the pathological effects of type-2 diabetes in the progression of a systemic inflammatory disease with a development of neuropathy, and fully developing into cardiovascular disease.  It also identifies a systemic relationship to the development of chronic obstructive pulmonary disease (COPD).

The more we learn about diabetes, we learn about its generalized systemic effects.

This article has the following SIX Parts:

Part 1. Role of Autonomic Cardiovascular Neuropathy in Pathogenesis of ischemic heart disease in patients with diabetes mellitus

Part 2. A Longitudinal Cohort Study of the Cardiovascular Experience of Individuals at High Risk for Diabetes

Part 3.  Clinical significance of cardiovascular dysmetabolic syndrome

Part 4.   Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease

Part 5.   How to use C-reactive protein in acute coronary care

Part 6.  Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

INTRODUCTION

Type 2 diabetes mellitus is a common chronic disease which develops insidiously over time, and is associated with obesity, nutritional imbalance (high fructose beverages, high starch and processed foods, carbohydrate excess intake, and an imbalance of proinflammatory to anti-inflammatory polyunsaturated  fatty acids), which makes it an acquired and manageable disease.  The long term effects of T2DM is played out on cardiovascular disease and stroke-risk, obstructive sleep apnea, progressive renal insufficiency, development of neuropathy, congestive heart failure and chronic obstructive pulmonary disease, all of which are occuring related to an systemic inflammatory condition that proceeds for some time prior to the identification of overt diabetes.
A detailed story of a significant part of these associations continues in the SIX Part series.

Part 1. Role of Autonomic Cardiovascular Neuropathy in Pathogenesis of ischemic heart disease in patients with diabetes mellitus

This article is an abstract only of a related publication of the pathogenesis of autonomic neuropathy in diabetics leading to ischemic heart disease.

Subjects: Medicine (General), Medicine, Medicine (General),
Health Sciences Authors: Popović-Pejičić Snježana, Todorović-Đilas Ljiljana, Pantelinac Pavle
Publisher: Društvo lekara Vojvodine Srpskog lekarskog društva
Publication: Medicinski Pregled 2006; 59(3-4): Pp 118-123 (2006) ISSN(s): 0025-8105  Added to DOAJ: 2010-11-11
http://dx.doi.org/10.2298/MPNS0604118P  http://www.doiserbia.nb.rs/img/doi/0025-8105/2006/0025-81050604118P.pdf

Keywords: diabetes mellitus, autonomic nervous system diseases, heart diseases, myocardial ischemia, comorbidity

Introduction.

Diabetes is strongly associated with macrovascular complications, among which

• ischemic heart disease is the major cause of mortality.

Autonomic neuropathy increases the risk of complications, which calls for an early diagnosis. The aim of this study was to determine

• both presence and extent of cardiac autonomic neuropathy,

in regard to the type of diabetes mellitus, as well as

• its correlation with coronary disease and
• major cardiovascular risk factors.

Material and methods. We have examined 90 subjects, classified into three groups, with 30 patients each: those with type 1 diabetes, type 2 diabetes and control group of healthy subjects. All patients underwent

• cardiovascular tests (Valsalva maneuver, deep breathing test, response to standing, blood pressure response to standing sustained, handgrip test),
• electrocardiogram,
• treadmill exercise test and
• filled out a questionnaire referring to major cardiovascular risk factors: smoking, obesity, hypertension, and dyslipidemia.

Results. Our results showed that cardiovascular autonomic neuropathy was

• more frequent in type 2 diabetes,
• manifesting as autonomic neuropathy.

In patients with autonomic neuropathy, regardless of the type of diabetes,

• the treadmill test was positive, i.e. strongly correlating with coronary disease.

In regard to coronary disease risk factors,

• the most frequent correlation was found for obesity and hypertension.

Discussion

Cardiovascular autonomic neuropathy is considered to be the principal cause of arteriosclerosis and coronary disease. Our results showed that the occurrence of cardiovascular autonomic neuropathy increases the risk of coronary disease due to dysfunction of autonomic nervous system.

Conclusions

Cardiovascular autonomic neuropathy is a common complication of diabetes that significantly correlates with coronary disease. Early diagnosis of cardiovascular autonomic neuropathy points to increased cardiovascular risk, providing a basis for preventive and therapeutic measures.

Part 2. A Longitudinal Cohort Study of the Cardiovascular Experience of Individuals at High Risk for Diabetes

This second part is a description of a longitudinal cohort study of individuals at high-risk for diabetes.  Unlike the SSA study, the study is not focused on protein-energy malnutrition.

Protocol for ADDITION-PRO: a longitudinal cohort study of the cardiovascular experience of individuals at high risk for diabetes recruited from Danish primary care

Subjects: Public aspects of medicine, Medicine, Public Health, Health Sciences
Authors: Johansen NB, Hansen Anne-Louise S, Jensen TM, Philipsen A, Rasmussen SS, Jørgensen ME, Simmons RK, Lauritzen T, Sandbæk A, Witte DR
Publisher: BioMed Central    Date of publication: 2012 Dec Published in: BMC Public Health 2012; 12(1): 1078    ISSN(s): 1471-2458   Added to DOAJ: 2013-03-12 http://dx.doi.org/10.1186/1471-2458-12-1078       http://www.biomedcentral.com/1471-2458/12/1078

Keywords: Diabetes, Cardiovascular disease, Primary care, Complications, Microvascular, Impaired fasting glucose, Impaired glucose intolerance, Aortic stiffness, Physical activity, Body composition

Background

Screening programmes for type 2 diabetes inevitably find more individuals at high risk for diabetes than people with undiagnosed prevalent disease. While well established guidelines for the treatment of diabetes exist, less is known about treatment or prevention strategies for individuals found at high risk following screening. In order to make better use of the opportunities for primary prevention of diabetes and its complications among this high risk group, it is important to

• quantify diabetes progression rates and to examine
• the development of early markers of cardiovascular disease and
• microvascular diabetic complications.

We also require a better understanding of the

• mechanisms that underlie and drive early changes in cardiometabolic physiology.

The ADDITION-PRO study was designed to address these issues among individuals at different levels of diabetes risk recruited from Danish primary care.

Methods/Design

ADDITION-PRO is a population-based, longitudinal cohort study of individuals at high risk for diabetes. 16,136 eligible individuals were identified at high risk following participation in a stepwise screening programme in Danish general practice between 2001 and 2006.

• All individuals with impaired glucose regulation at screening,
• those who developed diabetes following screening, and
• a random sub-sample of those at lower levels of diabetes risk

were invited to attend a follow-up health assessment in 2009–2011 (n = 4,188), of whom 2,082 (50%) attended. The health assessment included

• detailed measurement of anthropometry,
• body composition,
• biochemistry,
• physical activity and
• cardiovascular risk factors including aortic stiffness and central blood pressure.

All ADDITION-PRO participants are being followed for incident cardiovascular disease and death.

Discussion

The ADDITION-PRO study is designed to increase

• understanding of cardiovascular risk and
• its underlying mechanisms among individuals at high risk of diabetes.

Key features of this study include

• (i) a carefully characterised cohort at different levels of diabetes risk;
• (ii) detailed measurement of cardiovascular and metabolic risk factors;
• (iii) objective measurement of physical activity behaviour; and
• (iv) long-term follow-up of hard clinical outcomes including mortality and cardiovascular disease.

Results will inform policy recommendations concerning cardiovascular risk reduction and treatment among individuals at high risk for diabetes. The detailed phenotyping of this cohort will also allow a number of research questions concerning early changes in cardiometabolic physiology to be addressed.

Part 3.  Clinical significance of cardiovascular dysmetabolic syndrome

This study also addresses the issue of diabetes insulin resistance leading to cardiovascular dysmetabolic syndrome.

Subjects: Diseases of the circulatory (Cardiovascular) system,
Specialties of internal medicine, Internal medicine, Medicine, Cardiovascular, Medicine (General), Health Sciences
Authors: Deedwania Prakash C Publisher: BioMed Central            Date of publication: 2002 Jan
Published in: Trials 2002; 3: 1(2)   ISSN(s): 1468-6708  Added to DOAJ: 2004-06-03
http://dx.doi.org/10.1186/1468-6708-3-2   http://cvm.controlled-trials.com/content/3/1/2

Keywords: cardiovascular dysmetabolic syndrome, coronary heart disease, diabetes mellitus, hyperinsulinemia, insulin resistance

Although diabetes mellitus is predominantly a metabolic disorder,

• recent data suggest that it is as much a vascular disorder.
• Cardiovascular complications are the leading cause
  • of death and disability in patients with diabetes mellitus.

A number of recent reports have emphasized that

• many patients already have atherosclerosis in progression
• at the time they are diagnosed with clinical evidence of diabetes mellitus.

The increased risk of atherosclerosis and cardiovascular complications in diabetic patients is related to

• the frequently associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and endothelial dysfunction.

The evolving knowledge regarding the variety of

• metabolic,
• hormonal, and
• hemodynamic abnormalities in patients with diabetes mellitus

has led to efforts designed for early identification of individuals at risk of subsequent disease. It has been suggested that

• insulin resistance, the key abnormality in type II diabetes,
• often precedes clinical features of diabetes by 5–6 years.

Careful attention to the criteria described for the cardiovascular dysmetabolic syndrome

• should help identify those at risk at an early stage.

The application of nonpharmacologic as well as newer emerging pharmacologic therapies can have beneficial effects

• in individuals with cardiovascular dysmetabolic syndrome and/or diabetes mellitus
• by improving insulin sensitivity and related abnormalities.

Early identification and implementation of appropriate therapeutic strategies would be necessary

• to contain the emerging new epidemic of cardiovascular disease related to diabetes.

Part 4.   Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease

Subjects: Public aspects of medicine, Medicine, Public Health, Health Sciences
Authors: Siren Reijo, Eriksson Johan G, Vanhanen Hannu
Publisher: BioMed Central      Date of publication: 2012 Aug
Published in: BMC Public Health 2012; 12: 1(631)    ISSN(s): 1471-2458   Added to DOAJ: 2013-03-12
http://dx.doi.org/10.1186/1471-2458-12-631    http://www.biomedcentral.com/1471-2458/12/631

Keywords: Waist circumference, Type 2 diabetes, Cardiovascular disease, Middle-aged men

Background

Abdominal obesity is a more important risk factor than overall obesity in

• predicting the development of type 2 diabetes and cardiovascular disease.

From a preventive and public health point of view it is crucial that

• risk factors are identified at an early stage,
• in order to change and modify behaviour and lifestyle in high risk individuals.

Methods

Data from a community based study was used to assess

• the risk for type 2 diabetes,
• cardiovascular disease and
• prevalence of metabolic syndrome in middle-aged men.

In order to identify those with increased risk for type 2 diabetes and/or cardiovascular disease

• sensitivity and specificity analysis were performed, including
• calculation of positive and negative predictive values, and
• corresponding 95% CI for eleven different cut-off points,
  • with 1 cm intervals (92 to 102 cm), for waist circumference.

Results

A waist circumference ≥94 cm in middle-aged men,

• identified those with increased risk for type 2 diabetes
• and/or for cardiovascular disease

with a sensitivity of 84.4% (95% CI 76.4% to 90.0%), and a specificity of 78.2% (95% CI 68.4% to 85.5%). The positive predictive value was 82.9% (95% CI 74.8% to 88.8%), and negative predictive value 80.0% (95% CI 70.3% to 87.1%), respectively .

Conclusions

Measurement of waist circumference in middle-aged men

• is a reliable test to identify individuals at increased risk for type 2 diabetes and cardiovascular disease.

This measurement should be used more frequently in daily practice in primary care

• in order to identify individuals at risk and when planning health counselling and interventions.

Part 5.  How to use C-reactive protein in acute coronary care

Luigi M. Biasucci, Wolfgang Koenig, Johannes Mair, Christian Mueller, Mario Plebani, Bertil Lindahl, Nader Rifai,Per Venge,Christian Hamm, and the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association of the European Society of Cardiology
Department of Cardiology B, Aarhus University Hospital, Tage Hansens Gade2, Aarhus DK-8000,Denmark; Germany, U.K., U.S., Italy
European Heart Journal Advance Access published Nov 7, 2013.  Current Opinion.  http://dx.doi.org/10.1093/eurheartj/eht435

Introduction

 C-reactive protein (CRP) is an acute phase protein and an established marker for detection, risk stratification, and monitoring of infections, and inflammatory and necrotic processes.. Because C-reactive protein is sensitive but not specific, its values must be nterpreted  in the clinical context. Inpatients with acute myocardial infarction (AMI), CRP increases within 4–6h of symptoms, peaks 2–4 days later,and returns to baseline after 7–10 days.

CRP has gained interest recently as a marker for risk stratification in acute coronary syndrome (ACS) when measured by high-sensitivity CRP assays. These assays have greater analytical sensitivity and reliably measure CRP concentrations within the reference range with low imprecision (5–10%). Because of evidence that atherosclerosis is an inflammatory disease, high-sensitivity CRP can be used as a biomarker of risk
in primary prevention and in patients with known cardiovascular disease. The aim of this review is to evaluate the use of CRP in patients with acute coronary disease.

The in-vitro stability of high-sensitivity C-reactive protein is excellent. Specific blood sampling conditions aren’t necessary.  However, retesting may be necessary with some assays if there is marked lipaemia.  Baseline and subsequent measures are in good for agreement for risk stratification despite biological variability of 30–60%.

The upper reference limit is method-dependent but usually 8mg/L for standard assays. The distribution of high-sensitivity CRP concentrations is skewed in both genders with a 50th percentile of_1.5mg/L (excluding women on hormone replacement therapy). Race differences have been reported. Most studies have reported no relationship with age,  but to circadian and seasonal variation. CRP concentrations are increased by smoking, obesity, and hormone replacement therapy and reduced by exercise, moderate alcohol drinking, and statin use. Correction for these factors is essential in reference range studies. CRP assays are not standardized. We recommend  the use of third-generation high-sensitivity CRP assays that combine features of standard and high-sensitivity CRP assays.  Required assay precision should be < 10% in the range of 3 and 10 mg/L.

Biochemical and analytical issues

Critical clinical concepts

(1) CRP concentrations are reported in mg/L
(2) CRP test results are method-dependent

•  classification of patients into risk categories is usually comparable

(3) Third generation CRP assay are recommended
(4) No specific patient preparation before blood sampling is necessary
(5) The in-vitro stability of CRP is high

This is only a portion of the published concensus document. What is relevant to this discussion is that the hs-CRP is an extremely valuable marker for inflammatory disease.  It is not ordered often enough because of the broad range of values that we have become accustomed to for years, and it is elevated in rheumatologic conditions, but even then, it is widely used in pediatrics because children may present with rapidly emergent sepsis with very minimal sympoms.
The hs-CRP has opened a window to subliminal inflammatory disease that is diabetes, with accompanied arteriolar endothelial inflammation.

Part 6.  Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony

Subjects: Diseases of the circulatory (Cardiovascular) system,
Specialties of internal medicine, Internal medicine, Medicine, Cardiovascular, Medicine (General), Health Sciences
Authors: Mirrakhimov Aibek E
Publisher: BioMed Central      Date of publication: Oct 2012   ISSN(s): 1475-2840
Published in: Cardiovascular Diabetology 2012; 11(1):132   Added to DOAJ: 2013-03-12
http://dx.doi.org/10.1186/1475-2840-11-132      http://www.cardiab.com/content/11/1/132

Keywords: COPD, Dysglycemia, Insulin resistance, Obesity, Metabolic syndrome, Diabetes mellitus endothelial dysfunction, Vasculopathy

Chronic obstructive pulmonary disease, metabolic syndrome and diabetes mellitus

• are common and underdiagnosed medical conditions.

It was predicted that chronic obstructive pulmonary disease

• will be the third leading cause of death worldwide by 2020.

The healthcare burden of this disease is even greater

• if we consider the significant impact of chronic obstructive pulmonary disease on
  • the cardiovascular morbidity and mortality.

Chronic obstructive pulmonary disease

• may be considered as a novel risk factor for new onset type 2 diabetes mellitus via

multiple pathophysiological alterations such as:

1. inflammation and oxidative stress,
2. insulin resistance,
3. weight gain and
4. alterations in metabolism of adipokines.

On the other hand, diabetes may act as an independent factor,

• negatively affecting pulmonary structure and function.

Diabetes is associated with an increased risk of

1. pulmonary infections,
2. disease exacerbations and
3. worsened COPD outcomes.

On the top of that, coexistent OSA

• may increase the risk for type 2 DM in some individuals.

The current scientific data necessitate a greater outlook on chronic obstructive pulmonary disease and

• chronic obstructive pulmonary disease may be viewed as a risk factor for
• the new onset type 2 diabetes mellitus.

Conversely, both types of diabetes mellitus should be viewed as

• strong contributing factors for the development of obstructive lung disease.

Such approach can potentially improve the outcomes and medical control for both conditions,

• and, thus, decrease the healthcare burden of these major medical problems.

CONCLUSIONS

This discussion  presents a spectrum of cardiovascular risk associated with type 2 diabetes mellitus, with high risk for CVD, stroke, endothelial dysfunction, and an association with obesity, measured by waist circumference, and an underlying proinflammatory state that can be measured by CRP.

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Circulating Endothelial Progenitors Cells (cEPCs) as Biomarkers

Posted in Atherogenic Processes & Pathology, Best evidence, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Bone marrow derived cells, Cardiovascular Research, Chemical Genetics, Circulating Progenitor Cells, Curation, Cytoskeleton, Diagnostic Immunology, Discovery process, Endothelial cells, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Immunodiagnostics, Interviews with Scientific Leaders, Metabolomics, Nitric Oxide in Health and Disease, Nutrition, Origins of Cardiovascular Disease, Population Health Management, Nutrition and Phytochemistry, Proteomics, Technology Advance Assessment of, Translational Effectiveness, Translational Research, Translational Science, Umbilical cord cells, tagged CEC subtypes, cell function correlation, cell identification by labelling, Circulating Progenitor Endothelial Cells, endothelial cell, Endothelial progenitor cell, increased number of CECs, ischemic dardiac disease, myocardial infarction, target cell blockers on January 14, 2014| Leave a Comment »

Circulating Endothelial Progenitors Cells (cEPCs) as Biomarkers

Article Curator: Larry H. Bernstein, MD, FCAP

and

Topic Curator: Aviva Lev-Ari, PhD, RN

Article ID #105: Circulating Endothelial Progenitors Cells (cEPCs) as Biomarkers. Published on 1/14/2014

WordCloud Image Produced by Adam Tubman

Circulating progenitor cells have gained much interest rapidly in the past year primarily in identification of damaged tissue that has turnover of cells that are identifiable in the circulation.  This has to require a sensitivity for identification at one or two logs lower than circulating hematopoietic cells.  I mention this untested view only because cells of the circulation are detected routinely by automated hematology instruments like those of Beckman-Coulter and Siemens, with graphical presentation of results.  The Sysmex also reports immature granulocytes that are a small percent of the neutrophil count.  In the evaluation of leukemias, flow cytometry has been used for years, but require a preparative step.  Cell types have been identified by acidic and basic dye stains to identify basophilic, acidophilic and neutrophilic granulocyte series, and by size of the cell population, and nuclear features, differentiating mature and nucleated red cells, the granulocyte series, monocytes and lymphocytes, as well as platelets (aggregation gives an underestimate of platelet count).  But to detect cancer cells or damaged endothelial cells, the number of cells in the circulation requires and antibody to the surface with a visualizable ligand attached to an antibody for identification.  Visualization could be by a fluorophor, or perhaps a luciferase reaction.  Here are two articles that identify circulating endothelial cells, making them suitable for biomarkers of cardiovascular injury.  Whether they can detect early predictive ischemia, or frank AMI needs investigation.  The concept of piecemeal necrosis in the heart may be applicable to cardiomyocyte injury that is found unexpectedly at autopsy as “silent infarct”.

Circulating endothelial progenitors–cells as biomarkers

Rosenzweig, Anthony
N Engl J Med. 2005 Sep 8;353(10):1055-7

Comment on

Circulating endothelial progenitor cells and cardiovascular outcomes

[N Engl J Med. 2005]  PMID: 16148292 [PubMed – indexed for MEDLINE]

Endothelial injury and dysfunction are thought to be critical events in the  pathogenesis of atherosclerosis. Thus,

• understanding the mechanisms that  maintain and restore endothelial function
  • may have important clinical  implications.

A series of clinical and basic studies prompted by the discovery 

• of bone marrow derived endothelial progenitor cells1 have
• provided insights into these processes and
  • opened a door to the development of new therapeutic approaches.

Growing evidence suggests that bone marrow derived endothelial progenitor cells circulate in the blood and

• play an important role in the formation of new blood vessels as well as
• contribute to vascular homeostasis in the adult.

Circulating endothelial progenitor cells were initially identified

• through their expression of CD34
  (a surface marker common to hematopoietic stem cells and mature endothelial cells)
• and vascular endothelial cell growth-factor receptor 2
  (VEGFR2 or kinase-domain related [KDR] receptor),

but not of other markers seen on fully differentiated endothelial cells.1

Subsequent studies have also used other identifiers, such as

• the stem-cell marker CD133, and
• functional assays, including
  • the ability to form endothelial colonies.

Endothelial progenitor cells defined in these ways probably represent

• a heterogeneous population, which,
• in combination with the lack of a consensual definition,

complicates the interpretation of work in this field.

Nevertheless, numerous studies in animals have shown that endothelial  progenitor cells can integrate into new and existing blood vessels.2,3,4
Intravenous injection of cytokine-mobilized human endothelial progenitor cells

• improved myocardial neoangiogenesis and
• the recovery of functioning in a rat model of infarction.3

Repeated injection of bone marrow derived cells in a mouse model of atherosclerosis

• reduced the rate of plaque formation without altering serum lipids levels, and
• donor endothelial progenitor cells could subsequently be identified in the recipient’s blood vessels.4

Previous clinical studies have shown that

• traditional risk factors for coronary atherosclerosis
• are associated with low levels of circulating endothelial progenitor cells,5 whereas
• protective interventions, including statin therapy6 and exercise,7
  • appear to increase the supply of these cells.

Hill et al. found that even in healthy volunteers,

• levels of endothelial progenitor cells were inversely correlated with the Framingham risk score and
• actually appeared to predict vascular function better than the Framingham risk score.5

Together, these data suggest that circulating endothelial progenitor cells may participate

• not only in forming new blood vessels
• but also in maintaining the integrity and function of vascular  endothelium,

thereby mitigating disease processes such as atherosclerosis.

In this issue of the Journal, Werner and colleagues have further advanced our understanding of the clinical implications of endothelial progenitor cells.8 Endothelial progenitor cells were quantitated in 519 patients with coronary artery disease who

• were followed for one year after undergoing catheterization.

Patients with higher levels of endothelial progenitor cells had

• a reduced risk of death from cardiovascular causes and of
• the composite end point of major cardiovascular events.

These relationships were preserved even

• after adjustment for traditional risk factors and prognostic variables.

A similar relationship was seen

• whether endothelial progenitor cells were  identified by virtue of expression
  either of CD34 and KDR or of CD133 or
• because of their ability to form endothelial colonies,

further strengthening the authors’ conclusions. Repeated catheterization was not performed in this  cohort, so

• we do not know whether the reduction in clinical events reflected a slowed progression of atherosclerosis or some other clinical effect.

A  dissociation between anatomical measures of atherosclerosis and clinical events has been well documented in other settings.

Although this study is consistent with prior work suggesting that circulating endothelial progenitor cells may play a protective role in vascular homeostasis, other explanations

• for the association between endothelial progenitor number and outcome remain possible.

Changes in the number of endothelial progenitor cells and

• in clinical events might reflect a common underlying etiology,
  • • rather than a causal relation.

For example, a defect in the production of nitric oxide, which plays an important role

• in both the mobilization of endothelial progenitor cells9 and blood-vessel function, might account for both observations.

Similarly, the number of endothelial progenitor cells

• may mirror a person’s regenerative capacity more broadly and
• predict clinical events on that basis.

Even if endothelial progenitor cells are mechanistically linked to clinical cardiovascular events,

• such clinical studies do not distinguish between the possibility
• that the protection is mediated through the integration of endothelial  progenitor cells into blood vessels and

its possible mediation by other  mechanisms, such as the

• paracrine benefits of endothelial progenitor  cell secreted products.

Although such questions will undoubtedly continue to provide fertile ground  for fundamental investigation,

• the report by Werner and colleagues has more  immediate clinical implications.

First, it suggests that circulating cell  populations may represent a new class of biomarkers

• that naturally integrate  diverse genetic and environmental effects,
• thereby providing robust  physiological and prognostic insights.

Second, in the context of coronary  disease, the study shows that

• the number of endothelial progenitor cells is an independent predictor of hard clinical outcomes.

As with other biomarkers, a demonstration of clinical usefulness will ultimately require

• the examination of other patient populations, as well as
• a demonstration that clinical therapy can be guided and enhanced by this information.

Finally, the increased risk associated with reduced levels of endothelial progenitor cells

• supports the growing interest in the therapeutic potential of enhancing the level of these cells.

The most dramatic extension of this line of reasoning involves

transferring  bone marrow or peripheral blood cells that are likely to include endothelial  progenitor cells to patients with coronary artery disease. Although it would be premature to judge the clinical success of these strategies, early trials, including one randomized (though incompletely blinded) trial, have suggested

• at least short-term functional benefits of intracoronary infusion of bone marrow cells after acute infarction.10

Trials are planned to address more definitively the potential benefits of such cells

• in the settings of acute infarction and chronic ischemic cardiomyopathy.

Such efforts would be aided substantially by the identification of specific markers as well as

• an improved understanding of the role of subtypes of endothelial progenitor cells and
• of the mechanisms by which they work.

Ironically, the data presented by Werner and colleagues in combination with work showing

• the impaired functioning of endothelial progenitor cells in high-risk patients5 suggest
• that the patients most in need of endothelial progenitor cells may be
  • • those who are least able to donate them for autologous transplantation.

Whether these limitations can be overcome through

• ex vivo expansion or  genetic modification of endothelial progenitor cells is unclear.

In addition to possible cell-based therapies, work on endothelial progenitor cells provides yet another rationale

• for redoubling efforts to comply with established therapeutic guidelines,
• including lifestyle modifications and the use of statin therapy,
  • • both of which appear to enhance the number of circulating endothelial progenitor cells.

Whether there will be a downside to enhancing the number and function of  endothelial progenitor cells remains unclear,

• although obvious concerns  include exacerbating conditions that are characterized by adverse vessel  formation,
  • such as diabetic retinopathy and tumor angiogenesis.

Small studies have suggested an association between high levels of circulating endothelial progenitor cells and the risk of certain cancers, such as multiple myeloma.11 Moreover, studies in animals show that

• bone marrow derived endothelial progenitors participate in tumor angiogenesis, thereby
  • • enhancing tumor growth.12

In the study by Werner and colleagues,

• the number of deaths from cardiovascular causes among patients with high levels of endothelial progenitor cells
• was substantially lower than that among patients with lower levels of these cells,
• without a reduction in the risk of death overall.8

Although this finding could raise the specter of a counterbalancing adverse effect of endothelial progenitor cells,

• there was no apparent pattern in the deaths due to other causes,
• and no deaths from cancer were noted in this population.

It is possible that as we learn more about the biology of endothelial progenitor cells, there may be opportunities

• to target vessel formation more specifically.

In addition, therapeutic strategies

• tailored to individualized risk will undoubtedly help in practice.

For example, in the study by Werner et al.,

• patients in the group with the lowest baseline levels of endothelial progenitor cells
• had a risk of death from cardiovascular causes of 8.3 percent during one year of follow-up,
• suggesting that the benefits of enhancing the function and number of endothelial progenitor cells
  • • may well outweigh the risks in such high-risk populations.

Additional studies will be necessary to address these questions definitively. Larger studies

• of longer duration performed in different cohorts will be required to determine fully
  • the clinical usefulness of endothelial progenitor cells as a biomarker.

Rigorous interventional studies will indicate

• whether levels of endothelial progenitor cells can be used to guide therapy and
• whether cell transfer has a role in augmenting the levels of these cells.

Basic-science studies should help guide these clinical efforts by

• further defining the desirable subpopulations of endothelial progenitor cells and
• the mechanisms by which they mediate their effects.

By establishing a connection between circulating endothelial progenitor cells and hard clinical end points, Werner and colleagues

• provide a potent stimulus for clinical and basic studies to address these important issues.

Source Information

From the Program in Cardiovascular Gene Therapy, Massachusetts General  Hospital, and Harvard Medical School ― both in Boston.

References

Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor  endothelial cells for angiogenesis. Science 1997;275:964-967.

Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced  mobilization of bone marrow-derived endothelial progenitor cells for  neovascularization. Nat Med 1999;5:434-438.

Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7: 430-436.

Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 2003; 108: 457-463.

Hill JM, Zalos G, Halcox JPJ, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593-600.

Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial  progenitor cells by statin therapy in patients with stable coronary artery  disease. Circulation 2001; 103: 2885-2890.

Laufs U, Werner N, Link A, et al. Physical training increases endothelial  progenitor cells, inhibits neointima formation, and enhances angiogenesis.  Circulation 2004; 109: 220-226.

Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353: 999-1007.

Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med  2003; 9: 1370-1376.

Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow  cell transfer after myocardial infarction: the BOOST randomised controlled  clinical trial. Lancet 2004; 364: 141-148.

Zhang H, Vakil V, Braunstein M, et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood 2005; 105: 3286-3294.

Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001;7:1194-1201.

Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction.

Kelly Bethel, Madelyn S Luttgen, Samir Damani, Anand Kolatkar, Rachelle Lamy, Mohsen Sabouri-Ghomi, Sarah Topol, Eric J Topol, Peter Kuhn

Physical Biology (Impact Factor: 2.62). 01/2014; 11(1):016002. http://dx.doi.org/10.1088/1478-3975/11/1/016002
Source: PubMed

Elevated levels of circulating endothelial cells (CECs) occur in response to various pathological conditions including myocardial infarction (MI). Here, we adapted

• a fluid phase biopsy technology platform that successfully detects circulating tumor cells in the blood of cancer patients (HD-CTC assay),
• to create a high-definition circulating endothelial cell (HD-CEC) assay for the detection and characterization of CECs.

Peripheral blood samples were collected from 79 MI patients, 25 healthy controls and six patients undergoing vascular surgery (VS). CECs were defined

• by positive staining for DAPI, CD146 and von Willebrand Factor
• and negative staining for CD45.

In addition, CECs exhibited distinct morphological features that

• enable differentiation from surrounding white blood cells.

1. CECs were found both as individual cells and as aggregates.
2. CEC numbers were higher in MI patients compared with healthy controls.
3. VS patients had lower CEC counts when compared with MI patients

but were not different from healthy controls.

Both HD-CEC and CellSearch® assays could discriminate

• MI patients from healthy controls with comparable accuracy

but the HD-CEC assay exhibited

• higher specificity while maintaining high sensitivity.

Our HD-CEC assay may be used as a robust diagnostic biomarker in MI patients.

MicroRNA function in endothelial cells

Solving the mystery of an unknown target gene using microRNA Target Site Blockers

Dr. Virginie Mattot

Dr. Virgine Mattot works in the team “Angiogenesis, endothelium activation and Cancer” directed by Dr. Fabrice Soncin at the Institut de Biologie de Lille in France where she studies the roles played by microRNAs in endothelial cells during physiological and pathological processes such as angiogenesis or endothelium activation. She has been using Target Site Blockers to investigate the role of microRNAs on putative targets which functions are yet unknown.

What is the main focus of the research conducted in your lab?

We are studying endothelial cell functions with a particular interest

• in angiogenesis and endothelium activation during physiological and tumoral vascular development.

How did your research lead to the study of microRNAs?

A few years ago, we identified in my team

• a new endothelial cell-specific gene which harbors a microRNA in its intronic sequence.

We have since been working on understanding

• the functions of both this new gene and
• its intronic microRNA in endothelial cells

What is the aim of your current project?

While we were searching for the functions of the intronic microRNA,

• we identified an unknown gene as a putative target.

The aim of my project was to investigate if this unknown gene was actually a genuine target and

• if regulation of this gene by the microRNA was involved in endothelial cell function.

We had already characterized the endothelial cell phenotype associated with the inhibition of our intronic microRNA.

We then used miRCURY LNA™ Target Site Blockers to demonstrate

• that the expression of this unknown gene is actually controlled by this microRNA.

Further, we also demonstrated that the microRNA regulates

• specific endothelial cell properties through regulation of this unknown gene.

How did you perform the experiments and analyze the results?

LNA™ enhanced target site blockers (TSB) for our microRNA were designed by Exiqon.
We transfected the TSBs into endothelial cells using our standard procedure and

• analysed the induced phenotype.

As a control for these experiments, a mutated version of the TSB was designed by Exiqon and

• transfected into endothelial cells.

We first verified that this TSB was functional by

• analyzing the expression of the miRNA target
  • • against which the TSB was directed in transfected cells.

Finally, we showed that the TSB induced similar phenotypes as those found when we inhibited the microRNA in the same cells. 

What were some specific challenges in your experiments and how did you overcome them?

The fact that the target gene for our microRNA was unknown was a major challenge. Without specific available tools, like antibodies,

• it becomes difficult to demonstrate the effect of the microRNA on the gene in question and
• to show that the unknown gene is indeed responsible for the functions of the microRNA.

However through the use of specific target site blockers, we were able to demonstrate

• that this unknown gene was associated with the phenotype observed
  • when the microRNA was inhibited in endothelial cells.

How do you feel about your results so far?

We are very pleased with the results of the TSB experiments and

• altogether these results demonstrate that our miRNA of interest
• is functional in endothelial cells
  • through the regulation of a target gene with a previously unknown role.

What do you find to be the main benefits/advantage of the LNA™ microRNA target site blockers from Exiqon?

Target Site Blockers are efficient tools to demonstrate the

• specific involvement of putative microRNA targets
• in the function played by this microRNA.

The use of LNA™ allows the design of short oligonucleotides that are very specific and easy to work with. 

What would be your advice to colleagues about getting started with microRNA functional analysis?

In order to address the role played by a microRNA,

• it is essential to perform both gain and loss of functions experiments.

What are the next steps in the current project and how do you plan to perform them?

We plan to use microRNA inhibitor libraries to identify

• more microRNAs specifically involved in the processes that we currently study.

When and where will be hear /read more about your studies?

We are currently in the process of submitting a manuscript regarding the function of my microRNA of interest.

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Food Insecurity in Africa and GMOs

Posted in Chemical Genetics, Computational Biology/Systems and Bioinformatics, Genome Biology, Health Economics and Outcomes Research, Health Law & Patient Safety, Indigent Nutrition, Infectious Disease & New Antibiotic Targets, International Global Work in Pharmaceutical, Interviews with Scientific Leaders, Nutrition, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Technology Transfer: Biotech and Pharmaceutical, tagged agribusiness, farming and small farming, industrial GMOs, malnutrition, Sub-Saharan Africa, Synthetic biology, topsoil management, World Health Organization, world nutrition on January 13, 2014| Leave a Comment »

Food Insecurity in Africa and GMOs

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

Article ID #103: Food Insecurity in Africa and GMOs. Published on 1/13/2014

WordCloud Image Produced by Adam Tubman

 

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.

http://www.grandchallenges.org/SiteCollectionImages/gcgh_overview_large.jpg

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).

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