The 6th annual BRIght Futures Prize Competition features three compelling projects with the potential to solve vexing medical problems. The finalists, all BWH researchers and clinicians, were selected through a rigorous two-step scientific review process.
The BRIght Futures Prizes support investigators across the Brigham Research Institute (BRI) as they work to answer provocative questions or solve grand problems in medicine. Your vote will help decide which of these three projects will receive $100,000 towards their research. We will announce the winner at Discover Brigham, an event highlighting and celebrating research at Brigham and Women’s Hospital. The event is Thursday, November 9th from 12-6PM and is free and open to the public.
Read the Q&A with each of the finalists and vote for your favorite project.
BRIGHT FUTURES PRIZE FINALISTS
Ellen Bubrick, MD
Neurologist, Division of Epilepsy
Break the Shake: Ultrasound Treatment for Epilepsy
Collaborators: Nathan McDannold, PhD, Research Director, Therapeutic Ultrasound Lab and Focused Ultrasound Surgery, Spencer Brinker, PhD, Postdoctoral Research Fellow, Department of Radiology
Epilepsy, a disorder of recurrent seizures, is one of the most common neurologic disorders, affecting approximately 3 million Americans and 65 million people worldwide. Some patients with epilepsy become seizure-free with medication, but more than one-third of patients have persistent seizures, despite taking medication. Ongoing seizures can be very debilitating and even deadly, with more people dying each year of seizure-related injuries than from breast cancer. This patient population also has higher rates of depression and anxiety, overall lower quality of life, accidental death and an elevated suicide rate. Patients are also at risk of sudden unexpected death in epilepsy (SUDEP), a fatal complication that can take the lives of both adults and children with epilepsy.
Despite this, epilepsy research remains largely underfunded, and few new treatments are in the pipeline. We know, however, that becoming seizure-free earlier in the course of the disease may lessen the cognitive, behavioral and psychosocial problems experienced by epilepsy patients.
Many of these patients have few to no options to stop their seizures; medications are not effective and only a small percentage of patients are eligible for epilepsy surgery. Several invasive devices have been shown to be somewhat beneficial, though these are limited to very specific patient populations and responses vary.
We want to bring low-intensity focused ultrasound to patients who are suffering from epileptic seizures. High-intensity focused ultrasound has been hugely successful in treating other diseases, including Parkinson’s disease and brain tumors. The modified version with low intensity is a safe, noninvasive technique that works by neuromodulation, or mechanical disruption of brain networks, to treat the brain cells causing the seizures. This new form of ultrasound technology has not yet been offered to patients with epilepsy. We want to conduct a clinical trial to test this option as a treatment for patients who do not respond to medications.
This is likely to be a huge breakthrough in the treatment of epilepsy, especially for those patients who do not achieve seizure control with medications. This is a first-of-its-kind technology that may be able to provide patients with this devastating disorder some relief from seizures. It is also likely to be helpful in many other neurologic disorders, offering relief from the suffering that millions of patients experience.
Choi-Fong Cho, PhD
Neuroscientist, Department of Neurosurgery
Ready, Aim, Fire: Destroy Brain Cancer
Collaborators: E. Antonio Chiocca, MD, Chair of Neurosurgery, Bradley Pentelute, PhD, Associate Professor of Chemistry, Massachusetts Institute of Technology, Marcelo DiCarli, MD, Chief of Nuclear Medicine, Sean Lawler, PhD, Assistant Professor, Department of Neurosurgery
Advanced brain cancers, including glioblastoma, are often incurable and have a high mortality rate. Patients typically undergo surgery, followed by chemotherapy, radiotherapy or both. But even with this aggressive treatment strategy, the survival rate of patients has only improved slightly, from 11 months (with no treatment) to 14.6 months from the time of diagnosis. It is impossible to completely remove aggressive brain cancer cells by surgery because these cells invade the surrounding normal brain tissue and cannot be easily identified. Cancer drugs administered via the bloodstream are often unable to reach these cells, as the cells are protected by a highly evolved barrier called the blood-brain barrier, which isolates brain tissues from foreign molecules introduced through the blood stream. Our mission is to address these dire clinical challenges by developing new targeted therapies that can effectively cross the blood-brain barrier and selectively seek out and destroy brain tumor cells.
We have developed a unique molecule that can cross the blood-brain barrier, as well as identify and home in on brain cancer cells. This allows us to target only the tumor cells without harming healthy tissue. This tumor-homing “smart missile” is called BTP-7.
Our target is a protein signature that is present only on the surface of brain cancer cells; this is not found in healthy tissue. BTP-7 binds to this protein and then becomes internalized by the brain cancer cells. Our plan is to chemically fuse a chemotherapeutic drug or imaging agent onto BTP-7 – like attaching a warhead onto a missile. We will generate many different BTP-7 missiles containing various types of anti-cancer drug or imaging agent to enable us to selectively visualize and destroy the tumor.
Conventional chemotherapy drugs travel throughout the body and can also damage normal healthy cells, causing severe side effects in patients, Improving our ability to direct these drugs specifically to the tumor should enable us to increase treatment effectiveness while reducing the unwanted side effects of chemotherapy. Findings from our research could help us develop the next generation of therapeutics to extend the lives of patients with advanced brain cancer, as well as improve the quality of life of the patients and their families. Ultimately, we aim to advance precision medicine in neuro-oncology and abolish brain cancer in the future.
Yuhan Lee, PhD
Materials Scientist, Division of Engineering in Medicine
Surgery in a Pill: Reversing Type 2 Diabetes
Collaborators: Jeffrey Karp, PhD, Biomedical Engineer, Division of Engineering in Medicine (Principal Investigator), Ali Tavakkoli, MD, Gastrointestinal Surgeon, Department of Surgery (Principal Investigator)
The Type 2 diabetes epidemic is growing at an alarming rate: Every 6 seconds, someone dies from diabetes and its complications. There are many drugs available for treatment of diabetes, but diabetes management remains challenging. Poorly controlled diabetes leads to many health problems, including blindness, limb amputation and renal failure. Recently, surgeons have found that surgically re-routing the gastrointestinal tract can completely reverse diabetes. However, many patients with diabetes do not qualify for the surgeries or choose not to have them due to risks. There is an urgent need to deliver the benefits of bariatric surgery for patients with Type 2 diabetes but in a safer, noninvasive way.
Our idea is to package all the benefits of the surgery into a small pill. Before a meal, a patient could swallow a pill containing a substance that would coat the stomach and intestine, forming a temporary physical barrier. This blocks nutrient contact in the bowel during the meal and lowers blood glucose. The effect is similar to the results from surgery, but after a few hours the coating clears out from the gut. This solution is appealing because it’s safe and reversible, and stays only in the applied region rather than circulating throughout the body.
For more than six years, we have been developing a compound we call “LuCI,” short for Luminal Coating of Intestine. LuCI is a dried powder that can be ingested in the form of a pill or in a capsule. After patients take LuCI, it forms a viscus, sticky liquid that coats in the gut. In animal studies, this coating significantly reduced blood sugar levels for several hours after a meal with just one dose. Also, LuCI is based on an FDA-approved compound, which makes it much more likely that it will be safe to take.
Diabetes is recognized as a global epidemic affecting 450 million people worldwide, with this number estimated to increase to 640 million by 2040. While many medications are available, fewer than half of patients who take them achieve appropriate blood sugar control More challenging, three out of four patients who have diabetes live in low- and middle-income countries where access to some of the newer, more expensive mediations is limited. LuCI provides an alternative, more affordable therapeutic option that can be taken orally, and without systemic absorption, while providing the benefits of a major surgery.