Van Andel Research Institute’s Pathway of Hope Initiative achieves important research milestones

Research initiative focused on developing improved treatments for tuberous sclerosis complex patients brings hope on TSC Awareness Day

Grand Rapids, Mich. (May 14, 2014) – May 15th is Tuberous Sclerosis Complex Awareness Day, and in 2013 Van Andel Research Institute (VARI) launched the Pathway of Hope research initiative under the direction of Dr. Jeffrey MacKeigan, Associate Professor and Head of the Institute’s Laboratory of Systems Biology. The initiative involves a combination of basic biology, translational and clinical approaches, with the goal of developing new, effective treatments for individuals with tuberous sclerosis complex (TSC). TSC causes non-cancerous tumors in major organs, and patients afflicted with disease often suffer from epilepsy, learning disabilities and other complications. VARI’s Pathway of Hope project involves TSC experts and investigators from across the United States, with funding from the Michigan Strategic Fund and Blue Cross Blue Shield of Michigan, Michigan-based businesses Great Lakes Scrip, Rockford Construction, Colliers International, Team Hannah TSC and individual donors.

“I am extremely proud of the progress that our team has made over the past year. We have assembled truly phenomenal scientists and clinicians to deliver on an ambitious research agenda targeting new treatment options for TSC patients,” said MacKeigan.

The TSC research team screened multiple disease-relevant cell lines searching for novel genes not yet linked to TSC. The team uncovered several intriguing genes, and is in the midst of investigating these genes for their potential in new TSC treatment strategies. Collaborations with the University of Maryland, NYU Langone Medical Center and the University of Texas Houston enabled the team to obtain approximately 150 TSC tissue samples for further research studies.

High-quality DNA and RNA were extracted from the samples and sent to partners for cutting- edge, next-generation sequencing. The sequencing results and subsequent analysis is used by the Pathway of Hope team to identify mutations contributing to TSC tumor growth.

Katie Martin, Ph.D., scientific project leader in VAI’s Laboratory of Systems Biology, explains the importance of identifying driver mutations: “The molecular pathways driving tumors are going to be explored, with the team determining how the interruption of these processes could lead to new drugs for patients.”

The Pathway of Hope team has taken a more tangible approach for patients currently living with TSC, while continuing to investigate the molecular details of the disease. Through clinical collaborations with Helen DeVos Children’s Hospital in Grand Rapids, Mich. and the Cincinnati Children’s Hospital Medical Center, MacKeigan’s group opened a personalized medicine feasibility study. This pilot study evaluates the team’s ability to develop individualized treatment plans from patient genomic data. Enrolled patients provide blood and tissue samples, from which the team gleans relevant genetic information. A Molecular Tumor Board of experts then analyzes the information, and when possible, proposes a treatment plan matching unique patient mutations to available drugs. Although patients are not being treated in the feasibility study, the team is working toward the next phase, during which physicians can choose to implement the suggested personalized treatments.MacKeigan is optimistic about the potential for new treatment options.

“We are aggressively searching for those novel mutations that can provide significant therapeutic opportunities with real benefits for patients. Current TSC treatments shrink tumors, but it would be amazing if we could actually prevent or eliminate them all together,” said MacKeigan.

MacKeigan is hopeful that the Pathway of Hope research initiative will have important implications for other tumor disorders and human diseases. TSC has been called a ‘linchpin’ disease, which means that understanding more about TSC and how to treat it on the molecular level, could inform treatments for neurological disorders and cancer.

“On TSC Awareness Day, we should remember the patients living with the devastating effects of this disease. TSC research is important for their sake and it could also have a broader impact in the neurological and cancer fields,” said MacKeigan.

Individuals, businesses or companies interested in donating to the Pathway of Hope initiative can visit www.vai.org/tsc.

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About Van Andel Institute

Established by Jay and Betty Van Andel in 1996, Van Andel Institute is an independent research and educational organization based in Grand Rapids, Mich. Through biomedical research and science education, Van Andel Institute is committed to improving the health and enhancing the lives of current and future generations. Find out more about Van Andel Institute or donate by visiting www.vai.org. 100% To Research, Discovery & Hope®