Myriad RBM

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

Huckster — Mon, 25 Jul 2011 21:25:08 +0000

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

Huckster — Mon, 25 Jul 2011 21:22:29 +0000

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

Huckster — Mon, 11 Jul 2011 21:21:24 +0000

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

admin — Mon, 13 Jun 2011 05:48:36 +0000

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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Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker.

admin — Mon, 14 Mar 2011 17:58:30 +0000

This week’s paper was recently published in PLoS One as the researchers sought prognostic biomarkers for colorectal cancer metastases (CLM). Colorectal cancer is the third most common cancer in the world and metastasis of the disease makes it much harder to cure. Lin et al. compared tissue samples from patients with primary colorectal cancer (CRC) to samples from patients with CRC that had spread to the liver. Nearly 1000 genes showed differential expression between the two groups. Two proteins in particular, LEF1 and ostepontin, were found to be overexpressed in CLM. LEF1 overexpression was associated with a significantly worse survival rate and researchers suggest that it may serve as an important prognostic biomarker for CLM.

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Discussion question: Both of the differentially expressed proteins studied in this paper, LEF1 and osteopontin, are involved in the Wnt signaling pathway. What other proteins in this pathway are of interest for prognostic and diagnostic oncology research?