Showing 2 ideas for tag "calcification"

Goal 2: Reduce Human Disease

Discovering unique targets to treat and cure calcific aortic valve disease

Calcific aortic valve disease (CAVD) is a major contributor of cardiovascular morbidity and mortality. No therapeutic strategies currently exist to prevent or treat CAVD. The aortic valve represents a unique and highly dynamic tissue, and it is important to recognize that although CAVD shares many commonalities with atherosclerosis, traditional risk factors for atherosclerotic plaque development remain relatively poor... 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

CAVD progresses in three stages (New et al. Circ Res 2011): inflammation-mediated initiation, propagation of calcification, and end-stage stenosis. Reversibility at the end-stage remains unclear. To address this critical challenge, research is needed in:

- Early molecular imaging modalities
- Animal models that mimic human pathophysiology
- Factors differentiating valvular and vascular cell phenotypes
- Understanding the genesis of calcification
- CAVD biomarker identification

CAVD is directly responsible for more than 14,000 deaths annually in the USA alone. With valve replacement as the only available clinical option, patients often cope with a deteriorating quality of life until diminished valve function demands intervention. In fact, only 50% of patients with CAVD are referred for surgery, and only 40% are actually admitted for aortic valve replacement (Bach et al., JHVD 2011). In addition, the surgical valve replacement has limitations, including complications attributable to anticoagulation and the need for re-operation because of the limited lifespan of prosthetic valves (Yutzey et al, ATVB 2014). Therefore, the development of novel therapeutic strategies that target the early events in CAVD would represent a tremendous benefit for patients.

Feasibility and challenges of addressing this CQ or CC

The first step in addressing this challenge is to recognize that the aortic valve and CAVD are distinct from other cardiovascular diseases and allocate resources to address the unique properties. This is a feasible goal, but achieving tangible outcomes will require a multidisciplinary approach to study the areas of research outlined above. The NHLBI is well-suited to facilitate the requisite collaborative approach.

Name of idea submitter and other team members who worked on this idea Joshua D. Hutcheson, Ph.D. and Elena Aikawa, M.D., Ph.D.

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Goal 2: Reduce Human Disease

Understanding Glymphatic Pathways and Waste Clearance abnormalities in brain disease

Cerbrospinal fluid flow and waste clearance through glyphatic pathways are likely to be important in numerous brain diseases including such devastating diseases such as alzheimer's , parkinson's, stroke and migraine. However, relatively little is known about the brain's waste clearance mechanisms, and how failure in these systems may underlie brain disease. Build up of proteins and calcification have been shown to... 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

Studies on the etiology of migraine, stroke, motor disturbance, hydrocephalus, mental health and alzheimer's and numerous other brain diseases have overlooked the possible dysfuncton of brain waste clearance mechanisms. Similar to the case for renal failure, build up of toxic wastes in the brain may impact all aspects of brain health. A dedicated effort in understanding how the brain clears waste and the conditions that cause this to be imparied may open completely new avenues for treatment of debiltating brain diseases.

Feasibility and challenges of addressing this CQ or CC

Very little is known about the choroid plexus and other CSF generating tissues, the regulation of CSF compostioin and its flow through newly discovered glymphatic pathways. Furthermore, the challenge is determining whether deficiencies of these processes affect brain health. New technologies allow us to visualize the brain and CSF as never below, and can help us to make these connections. Furthermore, our advancing understanding of brain anatomy makes further investigation in this area timely and feasible.

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

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