Research UPDATE: Exploring Alternative Treatments

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In our third installment of the Mentored Young Investigator (MYI) blog series, we showcase 2009 MYI recipient, Joon Shim, Ph.D.  At the time of the award, Dr. Shim was a postdoctoral fellow at Boston Children’s Hospital. He is now a Research Assistant Professor at Indiana University.  He received an MYI grant for his study, “The role of angiogenesis in hydrocephalus.”  Angiogenesis is the process of forming new blood vessels.  It is essential for development and repair within the body. However, as a powerful physiological process, it can also, for example, be the transition from a tumor being benign to malignant. For this reason, angiogenesis has been linked to diseases including cancer, autoimmune diseases, age-related macular degeneration and atherosclerosis.  The most common pro-angiogenic factor is vascular endothelial growth factors (VEGF).  The study had three main aims: (1) quantify the level of VEGF in hydrocephalic patients; (2)
determine if infusion of VEGF into mice causes hydrocephalus; and (3) determine if infusion of anti-VEGF antibodies (bevacizumab) blocked ventriculomegaly. The significance of Dr. Shim’s research is the possibility of finding potential targets for drug treatments in hydrocephalus.

As a pro-angiogenic factor, VEGF promotes the process of new blood vessel development. It’s normal function is to signal the creation of these vessels during embryonic development or after an injury, among other examples. Results from the study found that VEGF was elevated in patients with hydrocephalus. VEGF infusion lead to ventriculomegaly (enlarged ventricles) and to ependymal changes, including loss of adhesion molecules and cilia.  It was also found that bevacizumab, a monocloncal antibody and anti-angiogenic (but not growth factor(s)), actually blocked enlargement of the ventricles.  This led to a couple of findings. First, if VEGF is elevated in the CSF of hydrocephalus patients, then it could be a potential biomarker for detecting hydrocephalus.  Second, if VEGF is contributing or causing the hydrocephalus, anti-angiogenic factors such as bevacizumab could, potentially, be used to block the hydrocephalus.

Dr. Shim sees that a big challenge in hydrocephalus research is the belief held by many that “hydrocephalus is successfully managed by shunts and is not a big problem as compared with cancer, Alzheimer’s and other brain disorders.”  This notion impedes research and discourages funding for hydrocephalus research.  Dr. Shim believes that study sections in federal grants designed specifically for ‘hydrocephalus research’ must be established to encourage and stimulate hydrocephalus research.

Findings from the study were published in Experimental Neurology: “VEGF, which is elevated in the CSF of patients with hydrocephalus, causes ventriculomegaly and ependymal changes in rats.”

Link to the abstract.

Mentored Young Investigator Award (MYI) program

The MYI Award program began in 2009 with the dual purpose of funding promising research relevant to hydrocephalus while fostering the development of young researchers. The award helps insure that qualified young scientists enter the field of hydrocephalus research and receive research training and experience under the guidance of highly trained, well-respected researchers who have demonstrated success in their field of research. At the completion of the grant period, our goal is that these young scientists become high-caliber, productive, independent researchers with an enduring focus on research relevant to hydrocephalus. Ultimately, it is hoped that this support will help these young scientists to make successful applications for an NIH K or R award to continue their research in hydrocephalus, thereby enriching the hydrocephalus research landscape.


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