Case Western Reserve University awarded $3.7 million to assess clinical trials at U.S. sites in wide-ranging effort to cure blood disease nationally, worldwide
The National Heart, Lung, and Blood Institute (NHLBI) has awarded Case Western Reserve University up to $3.7 million to assess emerging genome editing-based therapies being tested for curing sickle cell disease (SCD) at leading U.S research universities and hospitals.
initiative supports collaborative research to accelerate the development of genetic therapies within
five to 10 years.
The NIH, which spends about $100 million on sickle cell disease research each year, is aiming to have effective genetic therapies available within a decade. A $200 million initiative by NIH and Bill and Melinda Gates Foundation aims to make gene-based cures available globally, especially in sub-Saharan Africa, where the largest portion of cases exist.
Case Western Reserve in leading role
Umut Gurkan, the Warren E. Rupp Associate Professor in the Department of Mechanical and Aerospace Engineering in the Case School of Engineering, leads a university team that has developed micro-engineered tools to assess blood samples from patients before and after gene therapy treatment for SCD.
big-picture potential here is to test whether this is dream or reality when it
comes to gene therapy curing sickle cell,” Gurkan said. “We don’t know the
answers yet, but we have to ask whether these gene therapies are safe and effective
in alleviating the symptoms and curing the disease and if we have the right
First, those emerging gene therapies will be tested over
the next two years at clinics located at leading research universities,
including: Stanford University, the University of California-San
Francisco, Emory University, the University of North Carolina and the Albert
Einstein College of Medicine in New York City.
Blood samples will then be sent from these clinics to
Case Western Reserve for a sampling regimen generally known as “microfluid
biochip” testing, essentially employing the science of manipulating
and controlling fluids at an extremely small scale, less than the width of a
They will test for relative stickiness of the red blood cells,
the “hallmark of sickle cell,” Gurkan said, as well as for other biophysical markers
like density, “deformability” and whether the blood fails to flow through
microscopic, engineered capillaries mimicking human vasculature.
“If a curative therapy is successful and effective, we
should see a significant improvement in these vital properties of blood,” Gurkan
said. “Essentially we would like to objectively and quantitatively assess how
well the blood cells flow in tiny capillaries after a gene-based therapy.”
cell disease results from a single genetic mutation that causes a person’s red
blood cells to form an abnormal, sickle shape, according to the NIH. These
sickled cells can clog the small blood vessels and deprive tissues of oxygen.
In turn, this lack of oxygen wreaks havoc on the body, damaging organs, causing
severe pain and potentially leading to premature death.
according to the NIH, the only cure for sickle cell disease is a bone-marrow
transplant, a procedure in which a patient receives bone marrow from a healthy,
genetically-compatible sibling donor. However, transplants are too risky for
many adults, and only about 18% of children with the disease have a healthy,
matched sibling donor.
NIH initiative, then, focuses instead on gene therapies that modify the
patient’s own hematopoietic stem cells (HSCs), which make red and other blood
cells. These modified HSCs can then be given back to the patient via a bone
marrow transplant, making a cure available to more patients who lack a matched
Gurkan said Case Western Reserve and Northeast Ohio are
uniquely positioned to play a pivotal role in making genome-editing-based
therapies a reality, with national and global impact.
“We can become the epicenter of clinical blood testing,
quality control and outcome assessment for these emerging and definitive
therapies,” he said, adding that there are also specific translational and
commercial goals associated with the NIH-funded project.
The Case Western Reserve School of Medicine and University Hospitals have also played—and will continue to play—an important role in the development and initial clinical validation of these new blood tests, research funded by the NIH, National Science Foundation, and the Doris Duke Charitable Foundation, Gurkan said.
Stanton Gerson, director of both the Case Comprehensive Cancer Center and National Center for Regenerative Medicine, and who will become interim dean of the School of Medicine July 1, said the combined efforts will have global impact.
“As the genetic
cure for sickle cell becomes a clinical reality, longitudinal, simple and
accurate assessment and control through the tests that Dr. Gurkan has
developed becomes ideal and opens up this new treatment to patients across
the world,” Gerson said.
Gurkan said, that could mean one simple blood test to tell whether a patient is
benefitting from any given treatment. “Our team is committed to making these
new blood tests available for translation on global scale in both high- and
sickle cell might only be the beginning, he said.
“The reason the NIH is so focused on curing SCD is that it is the ‘poster child’ for gene-editing efforts,” Gurkan said. “If we can prove that we can cure an inherited mutation like SCD effectively and safely, then you convince the funders and the public that it is worth the expense and the effort to go after more complex inherited diseases which are less understood.”
And the work will take extensive collaboration, Gurkan said. The current project is being done with support from researchers from the Case Western Reserve School of Medicine; Stanford University School of Medicine; University Hospitals, Rainbow Babies and Children’s Hospital; University of California-San Francisco’s Benioff Children’s Hospital; Emory University School of Medicine, Children’s Healthcare of Atlanta; and Children’s Hospital of Montefiore, Albert Einstein College of Medicine.