Funding drives biomedical research, and research drives treatment innovation. Access to funds, particularly National Institute of Health (NIH) awards, is critical to move research forward. The 21st Century Cures Act, which passed the U.S. House on July 10, could give the NIH $8.75 billion more in new grants to disperse over the next five years, the largest increase since the Recovery Act of 2009.
How would those funds be used? Can research find a better way to treat patients? Prevent disease? Disseminate advances in medicine?
In 2014, Boston Children’s led the U.S. in NIH awards. Here’s a look at how a few research teams are leveraging NIH funding to improve care for both children and adults.
Uncovering common paths to autism
Award: $6.2M/5 years
Advances in genetics are starting to show us that autism spectrum disorder and intellectual disability (ASD/ID) encompass a spectrum of rare disorders. Some of these genetic causes of autism impair similar cellular pathways in the brain, all converging on the brain connections known as synapses.
The Developmental Synaptopathies Consortium, a group of 10 medical centers, is studying three rare genetic syndromes that often cause ASD/ID—tuberous sclerosis complex (caused by mutation in the TSC1 and TSC2 genes), Phelan-McDermid Syndrome (caused by mutations in the SHANK 3 gene) and PTEN Hamartoma Tumor Syndrome (caused by mutations in the PTEN gene).
The NIH has awarded Mustafa Sahin, MD, PhD, $6,227,903 over five years to investigate whether mutations in TSC 1/2, PTEN and SHANK3 share a common pathophysiology. In collaboration with the consortium, Sahin will mine data from a larger patient population to better understand shared mechanisms of autism and pave the way for shared therapies.
Personalized treatment for blinding eye diseases
Lead investigator: Robert D’Amato, MD, PhD
Award: $1.25M/5 years
A number of blinding eye diseases, including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration, involve inappropriate blood vessel growth (angiogenesis) in the eye.
Robert D’Amato, MD, PhD, has been awarded $250,000 per year from 2011 to 2016 to research the link. He has discovered the ability to grow blood vessels differs dramatically among different strains of mice and is genetically controlled.
The next phase of his research aims to identify the specific genetic alterations that influence angiogenesis in the mouse model, which could lead to the ability to identify these same genetic risks in humans. This would enable testing to identify people who are at high risk for uncontrolled angiogenesis and to develop personalized treatments to prevent its onset.
On the cusp of genetic therapies for sickle cell disease
Lead investigator: David Williams, MD
Award: $7M/5 years
Sickle cell disease, one of the most common single-gene diseases in the world, carries a health care price tag of $1 billion annually in the U.S. alone. Therapy has not changed substantially in decades except for the introduction of hydroxyurea. While this drug is a mainstay of treatment, many patients aren’t helped by it.
Now we are on the cusp of bringing high-tech genetic therapies to sickle cell disease, taking advantage of recent scientific breakthroughs. The NIH has awarded a group of investigators at Boston Children’s and Brigham and Women’s Hospital $7 million over five years for a multidisciplinary project designed to translate research into new treatments.
Project leader David A. Williams, MD, and his colleagues Ben Ebert, MD, PhD, Stuart Orkin, MD, and Vijay Sankaran, MD, PhD, plan to develop potentially curative sickle-cell gene therapy for the most severely affected patients as well as inexpensive, low-tech targeted oral treatments that could be used globally. The work builds on basic science discoveries by Sankaran and Orkin and translational work in Williams’ lab.
Williams anticipates rapid translation of scientific discoveries into pre-clinical and clinical testing and is working with the Food and Drug Administration on required approvals to open pilot gene therapy studies at Boston Children’s.