Tag: Parkinson’s disease

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2024 CAREER Award Recipient: Flavia Vitale

by Melissa Pappas

Neurological disorders such as epilepsy, Alzheimers, Parkinson’s and certain forms of dementia are the leading cause of disability and second-leading cause of disease worldwide. These disorders disproportionately affect low-resourced communities due to lack of access to specialized healthcare, and many of these complex diseases lack curative solutions. The need to address neurological disorders is high, yet current diagnostics and treatments are not effective for preventative or personalized care and are not accessible or affordable enough to meet the needs of more than 3 billion people living with neurological disorders. 

Flavia Vitale, Associate Professor in Bioengineering in Penn Engineering and in Neurology in Penn Medicine, works to meet this need, developing accessible and affordable solutions for the diagnosis, treatment and rehabilitation of people with neurological disorders. 

“I started my research career in biomedical engineering hoping to one day help humanity,” says Vitale, who is also a 2024 recipient of a National Science Foundation (NSF) CAREER Award for her work. “But it wasn’t until I gained a more diverse skill set during my doctoral and postdoctoral research across chemical engineering and materials science that I was able to do that in a real way.”

Vitale’s multidisciplinary skills are what allow her to develop devices that help people living with brain disorders. The CAREER Award is now helping her further apply those skills and actualize some of her first long-term research projects at Penn. 

“This CAREER Award will support my lab’s current research in leveraging innovation in materials and fabrication approaches to develop devices that are able to interface with and control different chemical and electrical signals inside the brain,” she says.

Focused primarily on understanding the brain activity involved in epilepsy-induced seizures, Vitale aims to design and develop brain-interface devices to pinpoint and suppress uncontrolled brain activity to prevent seizures from happening. Her work will lead to revolutionary health care for the 30% of epilepsy patients whose conditions are drug resistant. Currently those patients either wait out the uncontrolled brain activity and oftentimes life-threatening convulsions, or hope to be eligible for invasive surgeries to remove the part of the brain where seizures originate or to implant the seizure-controlling devices that are currently available.

Read the full story in Penn Engineering Today.

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“Switchable” Bispecific Antibodies Pave Way for Safer Cancer Treatment

by Nathi Magubane

Bispecific T cell engagers are emerging as a powerful class of immunotherapy to treat cancer but are sometimes hindered by unwanted outcomes, such as on-target, off-tumor toxicity; cytokine release syndrome; and neurotoxicity. Now, researchers Penn researchers have developed a novel “switchable” bispecific T cell engager that mitigates these negative effects by co-opting a drug already approved by the FDA. (Image: iStock / CIPhotos)

In the ever-evolving battle against cancer, immunotherapy presents a turning point. It began with harnessing the body’s immune system to fight cancer, a concept rooted more than a century ago but only gaining significant momentum in recent years. Pioneering this shift were therapies like CAR T cell therapy, which reprograms a patient’s T cells to attack cancer cells. Within this domain, bispecific T cell engagers, or bispecific antibodies, have emerged as effective treatments for many blood-borne cancers in the clinic and are being evaluated for solid tumor therapy.

These antibodies simultaneously latch onto both a cancer cell and a T cell, effectively bridging the gap between the two. This proximity triggers the T cells to unleash their lethal arsenal, thereby killing the cancer cells. However, bispecific T cell engagers, like many cancer therapies, face hurdles such as cell-specific targeting limitations, known as on-target off-tumor toxicity, which means the tumor is correctly targeted but so are other healthy cells in the body, leading to healthy tissue damage. Moreover, bispecific antibodies may also lead to immune system overactivation, a precursor for cytokine release syndrome (CRS), and neurotoxicity.

Now, researchers led by Michael Mitchell of the University of Pennsylvania have found a way to circumvent many of these deleterious effects by developing a bispecific T cell nanoengager that is equipped with an “off switch.” Their findings are published in Nature Biomedical Engineering.

“We’re excited to show that bispecific antibodies can be tweaked in a way that allows us to tap into their powerful cancer-killing potential without inducing toxicity to healthy tissues,” says Mitchell, associate professor of bioengineering at Penn’s School of Engineering and Applied Science. “This new controllable drug-delivery mechanism, which we call switchable bispecific T cell nanoengagers, or SiTEs, adds this switchable component to the antibody via administering an FDA-approved small-molecule drug, amantadine.”

Read the full story in Penn Today.

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Uncertainty Investigated by Neuroscience

uncertainty

 

Uncertainty is part of life, but the underlying neuroscience of how we make decisions under conditions of uncertainty is only beginning to be understood. In a paper published Monday by Nature Human Behaviour, new Penn Bioengineering faculty member and Penn Integrates Knowledge Professor Konrad Kording, Ph.D., and his coauthor, Iris Vilares, Ph.D., of University College London, offer additional evidence that dopamine lies at the heart of how the brain operates when there is a lack of certainty.

Drs. Kording and Vilares devised a simple computerized test that examined the extent to which test takers relied on previous knowledge vs. what they saw at the present moment. They then administered the test to a cohort of patients with Parkinson’s disease, a condition associated with depleted dopamine levels. The patients were tested both while taking dopaminergic medication and while off it. They found that dopaminergic medication caused the patients to pay greater attention to sensory (i.e., visual) information — an effect that diminished as the patients learned. Ultimately, the study provided evidence that dopamine levels were related to the tendency to rely on new information, also called likelihood uncertainty.

“Scientists believe that understanding uncertainty is key to understanding how the brain computes,” Dr. Kording says. “There are many theories in this space. We provide fairly clean evidence for one of them, which is that dopamine encodes likelihood uncertainty. This information could change the way people think about the manner in which the brain deals with uncertainty.”