As a Hartwell Investigator, Samagya Banskota and her collaborators will leverage a cutting-edge genome editing technique
By Lyn Markey
Starting around age six, certain children develop diabetes, followed by loss of vision and hearing, along with progressive nervous system dysfunction. These children are suffering from Wolfram syndrome (WS), a rare neurodegenerative disease. Most won’t live beyond age 30.
But with an award from the Hartwell Foundation, Boston University Assistant Professor Samagya Banskota (BME) and collaborators at Washington University at St. Louis are working on a novel method of developing treatments for WS and other “rare” genetic diseases that, taken together, affect millions of people. Funding research areas that include cancer, medical diagnostics, physiology, and neurobiology, the Hartwell Foundation seeks to identify and support research that has not yet qualified for significant funding from outside sources, and that has the potential to benefit children in the U.S. These awards can provide early career scientists with an opportunity to realize their goals and make a difference.
Building a convergent lab
Since joining the BME faculty of the BU College of Engineering last year, Banskota has been building her lab from the ground up to conduct research combining expertise in biomaterials design, synthetic biology, drug delivery and gene editing, in order to better understand and treat diseases.
“My lab works to translate genome-editing technologies into effective treatments for patients by better understanding barriers to in vivo—i.e., in a living organism—delivery,” says Banskota. “These technologies are designed to precisely correct mutations that cause diseases, which is especially important for people with rare genetic diseases who often have limited treatment options. The main challenge in developing these therapies is delivering them to the right tissues and cells within the body.”
To that end, the Hartwell Foundation, whose stated mission is “benefitting children by inspiring innovation and achievement,” is giving Banskota and her lab a Hartwell Individual Biomedical Research Award. Each year, the foundation selects 10 unique proposals that represent early-stage, innovative, and cutting-edge technology in medicine and biomedical engineering. Banskota’s team will receive at least $300,000 over three years.
Wolfram Syndrome, a progressive condition
The majority of WS cases are due to pathogenic mutations in the Wolfram syndrome 1 (WFS1) gene. The prognosis is currently poor, as there are limited therapeutic options with no definitive cure. Palliative strategies include small molecule drugs that reduce some of the symptoms, but there is no treatment available that can delay, halt, or reverse the progression of WS. Patients’ short life expectancy is due to continual symptom progression and complications caused by neurodegeneration. Banskota’s is collaborating with Fumihiko Urano, MD, PhD, a physician-scientist at WashU, and collectively they aim to address ways to halt neurodegeneration and develop life-saving treatment to fight WS. This progressive degenerative condition afflicts nearly 5,000 people in the U.S. today.
Base editing: correcting “typos” in genetic code
One way to improve genome-editing treatments is by creating delivery systems that make the treatments safer, more precise, and more versatile, so that they may be applied to a broader range of biological and clinical challenges. Recently such an approach was used to create a life-saving treatment for a 9 ½-month old boy who was born with a rare genetic disorder that affects just one in 1.3 million babies, and can be fatal. He became the first patient of any age to have a custom gene-editing treatment, according to his doctors. Correcting it requires pinpoint targeting in an approach called base editing, a technique that identifies and fixes an incorrect DNA letter among the 3 million in the human genome. The child received an infusion made just for him and designed to fix his precise mutation.
The potential for a cure
If Banskota and her collaborators lab are successful in developing and implementing precise genome editing strategy for WS, it will also help advance the technology for such technologies against other rare genetic diseases, providing affected children for the first time with a therapeutic option and the potential for a cure. Collectively, WS and other rare genetic disorders affect approximately 1 in 20 American children.