Biomarker panel helps predict heart failure outcome

Preliminary research indicates that a small panel of biomarkers targeting various biological pathways (e.g. inflammation, vascular, renal) may be useful in helping to predict adverse outcomes in patients with chronic heart failure. Information from a seven biomarker panel provided higher predictive accuracy than the currently validated Seattle Heart Failure Model. The researchers now hope to extend the utility of the model beyond its initial scope to include groups at risk for other types of heart failure.

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Adult Neurogenesis with Respect to Blood Proteins

Here is a very interesting article in Nature which takes a look at adult neurogenesis with respect to blood proteins. The researchers demonstrated a link between age-related molecular changes in the blood and the decline in synaptic plasticity and cognitive function associated with ageing. Using a technique called heterochronic parabiosis, they found that young mice which were sharing a systemic environment with older mice experienced cellular and cognitive changes similar to that of aged mice. Of particular note, the investigators found a correlation between the reduced neurogenesis and levels of several chemokines present in the plasma.

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Drug development for neuropsychiatric disorders is notoriously difficult, fraught with higher costs and devastating late-stage failures.

Despite the impact on society of these diseases and the overwhelming need for treatments, an increasing number of pharmaceutical companies are abandoning their development of drugs that target neurological and psychological diseases. Some of the difficulties that these drugs face are due in part to the complexity of the diseases being targeted coupled with clinical trials that include difficult to define end-points for patient improvement. Biomarkers, with many wide applications, may pose a solution to some of these problems.

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Discussion question: How helpful do you think biomarkers can be in the success of future neuropsychiatric drug development; either in patient selection, early detection, or determining the efficacy of these medicines? What is most important for these neuropsychiatric drugs to succeed?

VSNL1 gene and visinin-like-protein-1 Associated with Schizophrenia

Morphological changes in the developing brain may account for some of the cognitive deficits and psychosis present in patients with schizophrenia. The “reduced neuropil hypothesis” proposes that the decreased brain volume observed in schizophrenia patients is caused by a disruption in proper axonal and dendritic growth. Cellular processes that affect neuronal differentiation and development, like the cAMP pathway, may underlie some of the pathology. This paper investigates single nucleotide polymorphisms in the VSNL1 gene and the resulting gene product, shown here to regulate cAMP, and demonstrates an association with schizophrenia. Which other proteins, specifically those that play a role in neuronal metabolism, do you think are important in the pathophysiology of schizophrenia?

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Overgrowth of brain and increased activity of anabolic pathway linked to autism

Autism is a complex disease with a diverse phenotype and it is often described as a spectrum disorder due to this behavioral heterogeneity. While autism’s etiology is still unknown, some patients with the disease display excessive early growth of the brain. This paper investigates the secreted amyloid precursor protein-alpha (sAPPα), a protein also involved in Alzheimer’s disease, and finds a link between elevated levels of the protein and severe autism. The authors postulate that sAPPα leads to overgrowth in the brain of autistic patients by contributing to the anabolic environment. Other brain disorders such as schizophrenia and Alzheimer’s are associated with decreases in brain volume. How much overlap in the biochemical pathways and biomarkers is there in the literature (or would you expect) for these diverse cognitive disorders?

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Biomarker Pathway Analysis

Our growing understanding of protein interactions throughout the body is leading to the creation of biomarker pathways that demonstrate the convergence of seemingly disparate pathways. The study of complex disorders such as autism highlights this sort of approach (see link) and this macro-level, “forest before the trees” approach, opens up novel avenues of research. How valuable do you feel mapping these biomarker pathways will prove in understanding the etiology, choosing appropriate drug targets, or monitoring the therapy for diseases?

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