Showing 7 ideas for tag "personalized"

Goal 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

There is a strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

a. A new way to classify sleep disorders.
b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.
c. Identification of subgroups of patients who will have different approaches to diagnosis.
d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

Name of idea submitter and other team members who worked on this idea Sleep Research Society

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167 net votes
220 up votes
53 down votes
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Goal 3: Advance Translational Research

A Collaboration Market Place for Industry and Academia to advance Translational Medicine

There is a vast amount of data regarding specific gene and protein targets, especially in the post genomics era with many well validated targets, and even more "strong candidates". Drug companies have libraries of compounds that could be good inhibitors/enhancers for these new targets but lack an internal program, IP of the target, or a sufficiently large market to initiate risky and expensive drug screens, let alone... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

An NHLBI sponsored and funded "Market Place" could be set up to partner drug companies seeking funds to perform earlier phase screens with academic investigators seeking funds to learn more about their protein target or advance a therapy. NHLBI could fund a successfully paired collaboration up to 100% of the cost, with a sliding scale of matched-costs from the industrial partner based on their market capitalization (e.g. big Pharma at 100%, Medium Pharma at 50%, and early-stage Pharma at 0%)

Well thought-out global contractual agreements for "non-disclosure" and "IP sharing", beneficial to both parties before and after initial 'pairing' of a collaboration, would significantly enhance the speed and feasibility of the studies.

More compounds could be tested for more targets, addressing rarer conditions, or common conditions where only a small proportion of the affected cases are impacted by mutations or deficiency of the target proteins.

Drug companies would be incentivized to examine more targets without necessarily needing a large market for a future drug.

Later stage studies – pre-clinical, Phase 1, and Phase 2 – could then be re-championed at the Market Place for additional NHLBI funding, either with new partners or the same partners to further advance successful compounds.

Feasibility and challenges of addressing this CQ or CC

Contractual negotiations between Industry and Academia/Clinicians is a significant barrier to Translational Medicine and personalized medicine in particular.

Often ideas are not shared simply due to a lack of non-disclosure agreements in place. A Market-place to share ideas behind a well-structured “non-disclosure” firewall at the NHLBI website would facilitate the speed of discussion and stimulate collaboration.

Funding within industry can be limited by board and share-holder goals. There is typically little incentive to advance translational programs at early stages with no or limited medium or long-term financial benefits. Providing funding to facilitate and perform these research collaborations would incentivize Pharma to collaborate with academics who may hold IP or data on novel targets discovered with NHLBI funding.

Name of idea submitter and other team members who worked on this idea PhDIdeas

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27 net votes
45 up votes
18 down votes
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Goal 4: Develop Workforce and Resources

Preserving and promoting expertise in integrative physiology

From my perspective, one of the key “critical challenges” facing the NHLBI in particular, and medical science in general, is to avoid being blinded by the promises of the reductionists in the “personalized, precision medicine” of the future. In order to understand the advances being made at the molecular level, we need to preserve and promote expertise in truly integrative physiology, what I like to call “PHYSIOMICS”.... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Unfortunately, human physiologists are being squeezed out of the medical industrial complex by the basic scientists on one end, and the epidemiologists on the other. Most departments of medicine now require on 80/20 commitment to have a significant research component of an academic career, and it is becoming increasingly difficult for those few of us physiologists remaining to compete with the pressures of both research funding and clinical mandates. I urge the leadership at NHLBI to preserve a strong focus on human physiology, and continue to support the small, but high resolution studies that are required to answer key research questions. I would submit that studying an individual patient’s unique physiology is as much “personalized” or “precision” medicine as it is to read their genome. Remember, despite billions of dollars of research support, there remains nothing better to predict the risk of diabetes, than a simple measure of waist size!

Name of idea submitter and other team members who worked on this idea Benjamin Levine

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6 net votes
16 up votes
10 down votes
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Goal 1: Promote Human Health

Predictive analytics to engage healthy behaviors and maintain health while reducing cost

Predictive Health employs the principle that using modern health testing and predictive analytics will better define true health (not just absence of disease) and, in combination with large-scale data analytics, will facilitate predicting deviations from the healthy trajectory earlier than traditional disease diagnosis, thus allowing more effective and less costly interventions to maintain health. Predictive Health educates... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

By addressing this CC the health of the nation will be improved: better national and individual understanding of health, greater longevity of sustained health and productivity, reduced costs of healthcare by focusing on health than on disease diagnosis and management.

Feasibility and challenges of addressing this CQ or CC

The Emory/Georgia Tech Predictive Health Institute (http://predictivehealth.emory.edu) was founded ~10 years ago by launching educational (http://predictivehealth.emory.edu/education/index.html) and scientific (http://predictivehealth.emory.edu/chd/index.html) programs to achieve the Predictive Health goals. The scientific approach created a prospective longitudinal cohort of individuals who have been richly phenotyped according to traditional medical testing (clinical laboratory, stress testing, etc) and research testing (genomics, metabolomics, regenerative cell potential, oxidative stress) to create the deepest understanding of current and future health. The success of the Predictive Health Institute demonstrates the feasibility and potential success of such a critical challenge to both human health and healthcare expenditures.

Name of idea submitter and other team members who worked on this idea Greg Martin, for the Emory/Georgia Tech Predictive Health Institute

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5 net votes
9 up votes
4 down votes
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Goal 2: Reduce Human Disease

Influence of the Gut Microbiome on Pulmonary Immunity in HIV-Infected Individuals

It has become increasingly clear that gut microbiota have a tremendous impact on human health and disease. While it is well known that commensal gut bacteria are crucial in maintaining immune homeostasis in the intestine, there is also evidence of indirect effects on the lung. Multiple studies have shown that alterations in gut microbiota can lead to severe defects in pulmonary immune responses and reduced ability to... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

HIV-infected individuals are at significant risk of developing and dying from infectious and non-infectious pulmonary complications. Alteration of gut microbiota have been shown to have dramatic effects on pulmonary immunity and severity of lung infections. For instance, multiple studies have indicated that probiotic treatment with certain Lactobacillus and Bifidobacterium strains results in reduced incidence and severity of upper respiratory tract infections in children. Similarly, a recent study showed that treatment with the minimally absorbed antibiotic neomycin was associated with alterations in gut microbiota composition and concomitant reduced pulmonary immunity and the inability to control Influenza infection in mice. It was recently described that HIV infection is associated with a dramatic alteration in gut microbiota and that these changes persist with antiretroviral therapy (ART). Thus, it is important to understand how these alterations may effect lung immunity, since the majority of HIV-infected individuals develop pulmonary infections. Furthermore, gut microbiota contribute to development of non-infectious complications such as atherosclerosis, metabolic disease, obesity and diabetes. It is thus highly plausible that the gut microbiota may also play a role in the development of non-infectious complications of the lung such as Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension, the rates of which are elevated in HIV-infected individuals.

Feasibility and challenges of addressing this CQ or CC

A better understanding of how alterations in gut microbiota associated with HIV infection affects pulmonary infectious and noninfectious complication could lead to therapies to protect this “at risk” group. Furthermore, manipulation of the gut microbiota in HIV-infected individuals using pro- and/or pre-biotics, antibiotics or diet modification to a composition that is associated with increased pulmonary immunity, reduced infections and lung complications are all low risk therapeutic strategies that could substantially improve lung heath in these individuals.

Name of idea submitter and other team members who worked on this idea Brent Palmer (NHLBI-INHALD group member) and Catherine Lozupone

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3 net votes
7 up votes
4 down votes
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Goal 2: Reduce Human Disease

Balancing Risks and Benefits: How Do Clinical Guidelines in Cardiovascular Medicine Promote the Health of an Individual?

Much of the hopes for precision medicine (as outlined Dr. Dr. Collins) are based on deriving large amounts of genomic, proteomic, epigenomic and metabolomic data on large cohorts of patients. It will take decades to build these cohorts and even more time to analyze them and derive specific conclusions on how these will help individualize treatments.

However, there is a pressing need for how to individualize contemporary... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

Name of idea submitter and other team members who worked on this idea Jalees Rehman

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1 net vote
1 up votes
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Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

As detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

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9 up votes
11 down votes
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