USC Center for Neuronal Longevity (CNL) Pursues Transformative Advance in Prevention and Treatment of Neurodegenerative Diseases

By Azad M. Madni, GIBT Affiliated Faculty

The USC Center for Neuronal Longevity (CNL) has a specific mission: become a world-leading center of excellence with a focus on creating adaptive, interventional bioengineered systems for delivering electromagnetic fields to prevent and treat prevalent neurodegenerative diseases of the brain and retina that today have no foreseeable cure. 

Led by Mark Humayun, MD, PhD, and a team of world-class researchers with expertise in complementary disciplines, the center is pursuing a game-changing advance in preventing neuronal loss in neurodegenerative diseases. Unlike existing approaches that focus on developing neuroprosthesis by bypassing damaged tissues to restore senses such as hearing and sight and reduce Parkinson tremor, the CNL approach focuses on achieving “neuronal longevity” by preventing neuronal loss in neurodegenerative diseases. This research focus is based on a single key insight: lost neurons cannot be restored. CNL intends to create a new class of microscale and nanoscale engineered systems that, in their final incarnation will be controllable in part by widely available portable devices. These systems, embodying this key advance, are expected to induce primary healing and/or prevent further neuronal and functional loss. 

Gianluca Lazzi, PhD, and Arthur Toga, PhD serve as CNL deputy directors, bringing their scientific expertise and track records in leading successful interdisciplinary initiatives and institutes to CNL’s management structure. CNL’s convergent research themes are specifically intended to fill gaps and overcome limitations in existing technologies, while at the same time increasing understanding of molecular mechanisms involved in neuroprotection. The resulting “bioengineered systems for neuronal longevity” will exploit CNL’s expertise in engineering, neuroscience, data science, material science, and medicine in conjunction with deep knowledge of biology and biochemistry. Equally important, the CNL team’s expertise in STEM education and pedagogy will assure effective knowledge transfer within the team.

The key research pillars of CNL are:

  1. a systemic focus rooted in extending neuronal longevity, a departure from today’s corrective strategy that calls for bypassing damaged tissues
  2. a transdisciplinary team of researchers with complementary expertise and synergistic goals to pursue this revolutionary advance
  3. a combination of testbeds that enable the realization of bioengineered systems for controlled remodeling of the retina to treat blindness, and bioengineered multi-model stimulation systems to prevent neuronal degeneration
  4. an innovative workforce development strategy that accelerates the development of an interdisciplinary workforce that reflects diversity and a culture of inclusion

The CNL intends to accomplish both societal and scientific impact by minimizing the annual economic burden of neurodegeneration, while accelerating discovery of novel bioengineered systems and creation of new tools for collaborative technology validation. For additional information on CNL, please contact:

Clinical Trial Shows Promising Outcomes for Vision Loss Patients Receiving Stem Cell Implants

Researchers at the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics recently reported promising one-year follow up results of a clinical trial using stem cells to treat vision loss.

The phase 1/2a trial set out to assess the safety of a stem cell-based retinal implant the USC Ginsburg Institute team developed to treat dry age-related macular degeneration (dry AMD), which is one of the leading causes of vision loss. A total of 15 patients with severe vision loss underwent surgery at Keck Medicine of USC to receive a stem cell-based implant in their worse- seeing eye. One-year follow up results demonstrated that the implant was not only safe and well-tolerated, but also helped improve vision in its recipients.

Stem cells to rescue a degenerating eye

The disease process of dry AMD involves deterioration of a layer of cells called the retinal pigment epithelium (RPE). RPE cells nourish and support the photoreceptor cells that enable us to perceive light, so when they degenerate, eyesight follows suit. There are currently few medical interventions for the millions of patients who suffer from dry AMD, and given enough time, the disease ultimately progresses to blindness.

Physician-scientists at the USC Ginsburg Institute sought to revolutionize the treatment landscape for dry AMD by utilizing stem cells to replenish the deteriorating RPE cell layer of the retina. To do so, the research team developed a small scaffold made of synthetic material that is safe within the human body and can harbor RPE cells grown from stem cells in a lab. The scaffold is shaped like a champagne bottle and can be inserted into a patient’s retina using a precision tool designed by surgeon-scientists Amir Kashani, MD, PhD and Mark Humayun, MD, PhD at the USC Ginsburg Institute.

Restored sight on the horizons

Clinical trial patients receiving this novel implant were followed for a year post-operation and monitored for any health complications. Prior to surgery, all patients had severe, end-stage forms of dry AMD and were considered legally blind. The trial demonstrated that the implant can be used safely in dry AMD patients, and promisingly, it even resulted in improvements in eyesight in several cases. To help explain the mechanism by which trial patients achieved improvements in visual acuity, the researchers proposed that “dormant” photoreceptor cells in the degenerating area of the retina may be revived by the stem-cell derived implant.

This effort represents the first-ever clinical trial of a retinal implant to treat dry AMD. Its promising early outcomes will pave the way for future studies assessing the implant’s ability to restore eyesight in a much larger cohort of patients, with the ultimate goal of achieving FDA approval as a novel therapeutic for dry AMD.

“We are very hopeful about the results and future directions of this trial,” Humayun said. “There is currently a major unmet clinical need for treatments to help patients suffering from dry AMD, and this stem cell-based therapy represents a large stride in the right direction.”

Mark Humayun featured on NBC News for inventions to treat blindness

By Alexandra Demetriou

Mark Humayun, MD, PhD, recently appeared on NBC California Live in a feature highlighting the remarkable story of his patient, Anna Kuehl, who regained her eyesight thanks to a retinal implant invented by Humayun’s research team.

Anna, a mother of two living in Southern California with her husband, noticed that her vision had begun deteriorating drastically with age. At first, she needed a stronger eyeglass prescription; eventually, the center of her visual field darkened into a black spot of complete blindness. Her quality of life declined with her vision: she found herself unable to fulfill her job duties as a CPA, and she withdrew from social events because, as she explained to NBC California Live, it became difficult to enjoy herself when she could no longer recognize people’s faces.

Anna was diagnosed with a form of progressive blindness known as dry age-related macular degeneration (AMD), for which there was no existing cure. Anna, like the millions of other Americans diagnosed with dry AMD each year, expected that her vision would inevitably deteriorate until it was mostly overtaken by darkness.

Anna sought treatment at the USC Roski Eye Institute, where she met Dr. Humayun, a vitreoretinal surgeon and world-renown inventor of advanced medical implants intended to cure various forms of blindness. Fortunately for Anna, Humayun’s research team at the USC Ginsburg Institute for Biomedical Therapeutics had the perfect invention in the works: a stem cell-based retinal implant meant to help patients with Anna’s exact condition.

After meeting with Dr. Humayun, Anna was deemed a good candidate to receive one of the first implants available to patients. She underwent surgery at the USC Roski Eye Institute, and over time, she noticed a change in her eyesight. Whole faces of her loved ones reappeared, and the dark spot that used to dominate her vision receded.

Anna is once again able to appreciate the day-to-day joys that macular degeneration had stolen, such as watching ships sail across the horizon and appreciating the vividly colored flowers of her garden.

As for Humayun and his team, seeing success stories like Anna’s continues to fuel their dedication to curing blindness and bringing hope to patients living in darkness. As Humayun says, “To be able to make even a little bit of difference makes it all worthwhile for us.”

To watch the full feature on NBC California Live, click here.

Dr. Humayun on NBC California Live
From left to right: NBC California Live reporter Vicki Johnson, USC Roski Eye Institute patient Anna Kuehl, and Dr. Mark Humayun

Dr. Humayun featured on Walter Isaacson’s Trailblazers podcast



By Alexandra Demetriou

Mark Humayun, MD, PhD, was recently featured on Trailblazers, an original podcast hosted by former CNN chairman and CEO Walter Isaacson. The Trailblazers podcast features leaders across society who have shaken up their fields, innovated in ways many would think impossible and charged forward to pioneer changes that excite the way our world operates. Isaacson, who has written best-selling books on innovators ranging from Leonardo da Vinci to Steve Jobs, sat with Humayun to discuss his career as a world-renown ophthalmologist and inventor. The episode highlights the challenges and victories Humayun has encountered along his journey to reverse blindness and restore a glimmer of hope to vision loss patients living in complete darkness.

Isaacson opens the podcast episode, entitled “Eyesight: Vision’s Visionaries,” with the story of Humayun succeeding in his first attempt to use electrodes to stimulate vision during eye surgery. He recounts the miraculous moment in 1992 when Humayun confirmed that his patient, blind for 50 years, was able to see a small but encouraging flicker of light while lying on the operating table. That light, which his patient described as looking like “a candle far off in the distance on a dark night,” marked a turning point in Humayun’s career and a monumental step forward in the field of vision science.

Almost three decades later, Humayun continues to pioneer groundbreaking advancements in ophthalmology and vision restoration. Humayun is widely recognized for his invention of the world’s first artificial retina, which has restored partial vision to hundreds of patients who were previously completely blind. Humayun and his team continue working to surmount the challenges of recreating one of our most sophisticated senses using a network of electrodes, and their current studies are focused on increasing clarity and adding color vision to their artificial sight system. But perhaps the truest measure of Humayun’s success as a trailblazer lies in the most basic and human experiences his patients have regained thanks to their implants: patients often share stories of watching fireworks on the Fourth of July, appreciating the lights on a Christmas tree, or experiencing the joy of playing with their young grandchildren thanks to the gift of sight their implants have given them.

“Everyone said, ‘This cannot happen,’” Humayun explains on Trailblazers, referring to the many obstacles that complicate creating a bionic eye implant, such as the delicacy of the human retina and the challenge of developing an electrode array capable of creating signals that the human brain can discern as meaningful images. “This was actually science fiction,” Humayun surmises, “and we made it science reality.”

To listen to the full podcast episode, click here.

USC research coalition uses computer models to accelerate advancements in vision science

By Alexandra Demetriou

The Argus II retinal prosthesis––often referred to as the world’s first “bionic eye” ––revolutionized the treatment of blindness. Throughout the past decade, this artificial retina, developed by Mark Humayun, MD, PhD and colleagues in collaboration with Second Sight Medical Products, has enabled hundreds of patients around the world with complete retinal blindness to regain partial eyesight.

The Argus II retinal prosthesis enables patients with complete retinal blindness to see the shapes of objects in their surroundings, such as this Fourth of July fireworks show.
The Argus II retinal prosthesis enables patients with complete retinal blindness to see the shapes of objects in their surroundings, such as this Fourth of July fireworks show.

The invention currently allows for black-and-white vision and particularly helps patients detect boundaries between objects in their surroundings. Using a combination of patient feedback and laboratory experiments, Humayun and his team at the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics continue to enhance the visual information retinal prostheses can offer patients.

In their latest work, USC Ginsburg Institute scientists, in collaboration with USC Institute for Technology and Medical Systems (ITEMS) engineers, have developed detailed computer models of the retina that enable them to test modifications to the prosthetic system with unprecedented ease and speed. These advances in computational modeling have enabled the team to make profound strides forward in understanding how to refine and build upon the device’s capabilities––with the long-term goal of restoring color vision and more precise visual details to patients with progressive blindness.

A look inside the “bionic eye”

At the most basic level, retinal prostheses work by converting visual information from the environment into electrical impulses that stimulate the otherwise blind retina. When these signals reach the vision center of the brain, known as the visual cortex, patients are able to perceive images and shapes from their surroundings.

The Argus II system involves a retinal implant––or, more specifically, a microelectrode array that sits atop and stimulates the retina––coupled with a pair of glasses outfitted with a camera that transmits signals to the implant. When the implant receives visual cues from the camera, it generates small electrical impulses that stimulate the patient’s retinal cells. This stimulation causes the patient to perceive a flash of light that vision scientists refer to as a phosphene.

Image of the Argus II retinal prosthesis, composed of a microelectrode array with thin projections that electrically stimulate the retina.
Image of the Argus II retinal prosthesis, composed of a microelectrode array with thin projections that electrically stimulate the retina.

Phosphenes should ideally appear as small, rounded dots when a single electrode stimulates the retina. In practice, however, patients sometimes perceive a dash instead of a dot––and the reason has to do with the way cells intermesh in the retina.

One of these cell types is the retinal ganglion cell, which plays an essential role in sending visual information from the eye to the brain. Retinal ganglion cells have rounded bodies with many thin projections branching off in different directions and one long projection that feeds information to the brain. These projections overlap and intertwine like the branches of trees in a densely wooded forest, so that when an electrode stimulates one of the retinal cells it often activates the projections of neighboring cells as well.

Example of a retinal ganglion cell, composed of a rounded, central body with numerous small projections and one long projection, or axon, that communicates with the brain (red). Vision scientists at the USC Ginsburg Institute are developing techniques to activate the bodies of specific cells without stimulating the projections of nearby cells, which will help sharpen the visual information that retinal prosthetics can offer patients.
Example of a retinal ganglion cell, composed of a rounded, central body with numerous small projections and one long projection, or axon, that communicates with the brain (red). Vision scientists at the USC Ginsburg Institute are developing techniques to activate the bodies of specific cells without stimulating the projections of nearby cells, which will help sharpen the visual information that retinal prosthetics can offer patients.

When electrical signals from the prosthesis stimulate both cell bodies and projections from nearby cells, patients perceive a dash of light, called an elongated phosphene, instead of a discrete dot. Humayun’s team set out to determine how to prevent elongated phosphenes from forming so patients could enjoy more refined, detailed vision. Doing so required devising an approach to target retinal cell bodies without activating neighboring cells in the process.

 

Computer models probe deeper into cellular behavior

To solve this challenge, the USC Ginsburg Institute and USC ITEMS teams first developed computational models to recreate different types of retinal ganglion cells and the patterns in which they overlap. Their models accounted for the relevant functional properties of retinal ganglion cells and could therefore respond to stimuli in ways that mimicked how real retinal ganglion cells would respond. Using these model systems, the scientists ran through a gamut of simulations to find a stimulation pattern that activated cell bodies while avoiding the large projections, known as axons, that other cells use to send visual information to the brain.

In one recent study, the team reported their discovery that very short-duration electrical pulses, as brief as 0.1 milliseconds, can selectively target the intended retinal ganglion cells’ bodies without activating their axons. Their models also enabled them to more accurately map out patterns of cellular activation that arise when shorter pulses are used to stimulate the retina. The researchers hope these, and future, findings can help resolve the problem of elongated phosphenes to ultimately offer patients enhanced visual resolution with a retinal prosthesis.

USC Ginsburg Institute and USC ITEMS scientists are also currently using their computational models of the retina to study possible ways of programming additional visual components, such as color, into the Argus II system. A 2020 study of theirs showed that a particular subtype of retinal ganglion cell, called a bistratified cell, is more responsive to high frequency stimulation than one of its counterparts known as a monostratified cell. Understanding these types of slight differences in responses may help the team improve the performance of retinal prosthetics to enable patients to detect color, contrast and edges of objects. Such research is still ongoing, but based on their preliminary findings, the team is hopeful for the ways they can continue enhancing visual perception for the hundreds of retinal prosthesis users who once lived in complete darkness.

Javad Paknahad, a PhD candidate at USC and the lead author on the aforementioned studies, emphasized how the “multi-scale” nature of these models, which account for the properties of single cells as well as the behavior of entire cell populations, makes this approach particularly valuable. He added that using computer models to study the retina allows their team to run experiments more efficiently, which ultimately accelerates scientific progress. “These multi-scale computational models end up saving a lot of time when doing experiments, because as you continue refining the model system and designing the right programs, you can more readily determine the best approaches to solving complex problems,” he said. “This makes computational modeling very powerful.”

 


Disclosure: Mark Humayun, MD, PhD, is a co-inventor of the Argus implant series.  He is a minority equity owner in Second Sight Medical Products, Inc. and receives royalty payment. 

Disclosures: Regenerative Patch Technologies LLC was founded by Mark Humayun, MD, PhD, and David R. Hinton, MD, from the University of Southern California, and Dennis O. Clegg, PhD, from the University of California, Santa Barbara. The technology to produce the stem cell–based retinal implant is exclusively licensed to Regenerative Patch Technologies LLC from the University of Southern California, the California Institute of Technology and the University of California, Santa Barbara. Humayun has an equity interest in and is a consultant for Regenerative Patch Technologies LLC.

Stanford study ranks Mark Humayun, MD, PhD on world’s top scientists list

By Alexandra Demetriou

Mark Humayun, MD, PhD, was included in a recent analysis out of Stanford University highlighting the world’s leading scientists across 22 fields of research and 176 sub-fields. Within the category of “ophthalmology & optometry,” Humayun ranks among the top 0.2% of his peers.

A recent Stanford study ranked Mark Humayun, MD, PhD, as one of the world's top scientists. (Image credit: Jill Greenberg)
A recent Stanford study ranked Mark Humayun, MD, PhD, as one of the world’s top scientists. (Image credit: Jill Greenberg)

The rankings were calculated based on metrics such as the number of times a scientist’s research has been cited throughout the individual’s career. The analysis also accounted for each person’s h-index score, which attempts to quantify the scientist’s research productivity balanced with the impact that the research has made on the scientific field.

Humayun, a vitreoretinal surgeon and prolific inventor of biomedical devices, is widely known for developing the world’s first artificial retina. In 2016, Humayun received the National Medal of Technology and Innovation from President Barack Obama for developing the Argus II retinal prosthesis, which restores partial vision to patients with total retinal blindness.

Some of Humayun’s other accolades include election to both the National Academy of Medicine (NAM) and National Academy of Engineering (NAE), the 2020 Medal for Innovations in Healthcare Technology from the Institute of Electrical and Electronics Engineers (IEEE), “Inventor of the Year” from R&D Magazine in 2005, and distinction as one of the top 1% of ophthalmologists in U.S. News & World Report.

Humayun currently serves as director of the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics and co-director of the USC Roski Eye Institute. He also holds the titles of University Professor and Cornelius J. Pings Chair in Biomedical Sciences at USC.

USC Ginsburg Institute for Biomedical Therapeutics Awards Inaugural Mordechai “Mort” Arditti Award for Excellence

By Alexandra Demetriou

On November 20th, 2020, the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics awarded its inaugural Mordechai “Mort” Arditti Award for Excellence to Alejandra Gonzalez-Calle, PhD, a postdoctoral researcher working to develop vision science innovations at the USC Ginsburg Institute.

Dr. Alejandra Gonzalez-Calle, the inaugural recipient of the Mordechai "Mort" Arditti Award for Excellence
Dr. Alejandra Gonzalez-Calle, the inaugural recipient of the Mordechai “Mort” Arditti Award for Excellence

Gonzalez-Calle grew up in Medellín, Colombia, and earned a BS in biomedical engineering at La Escuela de Ingenieria de Antioquia. As an undergraduate student, she planned to dedicate her career to developing affordable prosthetic limbs. After an accident that caused her to lose vision in her right eye, however, she redirected her energy toward advancing the field of vision science.

In 2009, Gonzalez-Calle reached out to Mark Humayun, MD, PhD, with the hope that she could pursue a research internship at his team’s USC lab. Humayun and his colleagues had an impressive record of churning out engineering-based solutions to address the biological anomalies causing vision loss, and Gonzalez-Calle aspired to join the ranks of this innovative team. That internship ultimately blossomed into over a decade and counting of collaboratively pioneering interdisciplinary, translational approaches to address some of the most confounding challenges in vision science. During that time, Gonzalez-Calle received one of the USC Viterbi School of Engineering’s highest research awards to support her pursuit of a master’s degree in biomedical engineering, and she later went on to earn a PhD in biomedical engineering in 2017.

Some of Gonzalez-Calle’s most meaningful experiences working with the USC Ginsburg Institute team include fine-tuning the Argus II retinal prosthesis to restore eyesight to patients suffering from complete retinal blindness and contributing to the development of a novel stem cell-based retinal implant for patients with AMD. Recently, she worked with a multidisciplinary team that was able to demonstrate, for the first time, that noninvasive electrical stimulation could be used to slow retinal degeneration in pre-clinical models.

Throughout the years spent working on these remarkable feats in biomedical engineering, Gonzalez-Calle has remained continuously inspired by seeing how the projects to which she has contributed can tangibly enhance patients’ lives. “Being able to see our projects evolve from the basic research stage to the point where they are implanted in patients, and then ultimately seeing how much of a difference these interventions can make in patients’ lives, is what makes me so passionate about what I’m doing,” Gonzalez-Calle says.

Receiving the inaugural Mordechai Arditti Award for Excellence carries special meaning for Gonzalez-Calle due to the fact that the late Arditti was an important mentor of hers throughout her training. Arditti, an electrical engineer by training, often contributed to and enhanced Gonzalez-Calle’s projects by helping to build circuits and essential electrical components of the biomedical devices on which Gonzalez-Calle worked. “He was such a special person for all of us,” Gonzalez-Calle remembers. “Besides being a mentor, he was also a friend to all the PhD students. I’m very grateful to receive this award and to feel like it’s coming from him, even though he’s not here with us anymore.”

USC Ginsburg Institute to host first-of-its-kind symposium on biomedical engineering in ophthalmology

By Alexandra Demetriou

The USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics recently received support from the National Eye Institute to host a first-of-its-kind symposium on the use of implantable and wearable devices in ophthalmology. The symposium, called “Abiotic-Biotic Interfaces for Ophthalmology,” will bring together world experts in clinical care, biomedical research, engineering, industry and pharmaceutics to brainstorm ways to transform the landscape of vision science.

The National Eye Institute, a division of the National Institutes of Health, will co-sponsor the symposium.
The National Eye Institute, a division of the National Institutes of Health, will co-sponsor the symposium. (Image: Federal Laboratory Consortium)

This conference comes at a time when innovations in machine learning and personalized medicine have opened new doors for the creation of therapeutic devices that blur the boundaries between human and machine. Scientists at the USC Ginsburg Institute believe ophthalmology is ripe for applying such innovations to treat vision loss. Their upcoming conference will encourage world-renowned experts and up-and-coming scientists to connect, collaborate and pursue innovations that fundamentally advance vision science and patient care.

The two-day symposium, scheduled for January 2021, will feature presentations on topics including implantable and wearable bioelectronic devices, nanoscale scaffolds for stem cell implantation, innovative drug delivery tools and cutting-edge gene therapies. Confirmed participants include leading experts from renowned institutions and numerous industrial partners.

A central goal of the symposium is fostering multidisciplinary collaboration spanning the academic, public and private sectors while creating mentorship opportunities for junior investigators entering the field of vision science. Trainees and early-career scientists will have the opportunity to present their work at the symposium, and one will receive the USC Ginsburg Award for Best Student Paper.

ibt-ginsburgs-drhumayun
Dr. Mark Humayun (left), USC Ginsburg Institute director and symposium organizer, with Dr. Allen and Charlotte Ginsburg, whose philanthropy established the USC Ginsburg Institute.

The organizing committee is composed of four leading vision scientists affiliated with the USC Ginsburg Institute: Mark Humayun, MD, PhD, director of the USC Ginsburg Institute and co-director of the USC Roski Eye Institute; Yu-Chong Tai, PhD, Caltech professor and expert in microelectromechanical systems for biology; Amir Kashani, MD, PhD, ophthalmologist with Keck Medicine of USC, associate professor of ophthalmology and clinical scholar at the Keck School of Medicine of USC; and Stan Louie, PharmD, professor of clinical pharmacy at the USC School of Pharmacy. All four scientists are actively involved in developing implantable and wearable devices to treat ophthalmologic and degenerative neurological diseases.

The committee will draw upon their decades of experience to lead discussions at the symposium that center on the translational, therapeutic applications of emerging abiotic-biotic technologies. This upcoming conference also builds upon their previous experiences hosting the inaugural USC Ginsburg Institute Symposium and speaking as guest lecturers at numerous external conferences throughout their individual careers.

“Our team looks forward to connecting with vision science colleagues from across the country to collaboratively work toward a brighter future for patients experiencing vision loss,” said Dr. Humayun. “There’s no better time than the present to take innovations from fields like artificial intelligence, engineering and medicine and apply them to the treatment of ophthalmic disease.”

Mark Humayun, MD, PhD, honored on “Southern California Super Doctors” list for 14th consecutive year

By Alexandra Demetriou

Renowned ophthalmologist and prolific inventor Mark S. Humayun, MD, PhD has been selected as one of the 2021 Southern California Super Doctors® by the independent publication Super Doctors.

The honor is meant to recognize “healthcare providers who have attained a high degree of peer recognition and professional achievement,” according to Super Doctors. Humayun, who serves as director of the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics and co-director of the USC Roski Eye Institute, has received this honor every year since the Super Doctors list was created in 2008.

MSH-whitecoat

Mark Humayun, MD, PhD, has been honored as a top physician on the “Southern California Super Doctors” list for the 14th consecutive year.

The selection process starts with nominations for each specialty category, in which colleagues can submit the names of physicians they themselves would see if they were in need of medical care. Super Doctors staff also nominate physicians based on honors, achievements and credentials gleaned from professional databases. Super Doctors research staff evaluate all candidates, and finalists are reviewed and scored by physician panelists to pare down the final list. The annually published Super Doctors list honors the highest-achieving physicians and represents approximately 5% of all doctors in their respective state or region.

“It is a great honor for me to be recognized amongst such great peers from all specialties of medicine,” Humayun said. “It encourages me to work even harder to help our patients in need.”

The Super Doctors list will be published in Super Doctors Southern California Magazine, delivered in January with the Los Angeles Times, and will also be available online at www.superdoctors.com.

USC Ginsburg Institute researchers help lead development of precision drug delivery tool to treat traumatic brain injury

By Alexandra Demetriou

An interdisciplinary team of researchers at the University of Southern California has developed a precision drug delivery tool to selectively treat areas of the brain damaged during a traumatic brain injury (TBI). The researchers anticipate that their rapidly deployable intervention could potentially help prevent long-term brain damage in the millions of Americans who sustain a TBI each year.

This invention has been tested using two different therapeutics, and the results appear in the journals Frontiers in Chemistry and Molecular Pharmaceutics.

Stopping the damage before it’s too late

The effects of TBIs on the American populace are nothing short of staggering. TBIs annually cause more deaths and lifelong disabilities than HIV/AIDS, breast cancer, multiple sclerosis and spinal cord injuries combined. Approximately one third of patients die due to secondary complications related to their TBIs, and in 2014, an average of 155 Americans died following a TBI each day. To compound this dramatic human toll, the economic burden of treating TBIs and their long-term side effects is estimated to be $60-76.5 billion each year.

The causes of TBIs range from falls and forceful sports collisions to car accidents and severe blows to the head. Side effects vary widely, from cognitive challenges and dizziness to emotional changes and depression that can endure for days, weeks, or even years after the initial trauma. If effective treatments are not rapidly deployed, a TBI can trigger biochemical changes and inflammatory responses that progressively worsen a patient’s brain damage. To prevent serious side effects, doctors recommend that patients receive treatment within the “golden hour” after sustaining the injury.

Despite the pressing need for effective and rapidly deployable therapies, there are currently no FDA-approved treatments specifically designed for TBIs. Some existing treatments rely on locating the injury within the skull and assessing the damage before proceeding, but this approach can rob precious time from clinicians attempting to stave off permanent brain damage.

A nanoscale solution to a widespread problem

An ideal treatment approach for TBIs would involve a fast-acting, safe, transportable and easily administered drug that could permeate the brain’s protective barrier at the site of damage. A team of USC scientists, led by researchers at the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics, has mobilized to meet this urgent clinical need: they recently developed a novel drug delivery tool designed to safely and rapidly treat regions of the brain damaged during a TBI.

The tool itself is known as a nanocage. As the name suggests, this nanoscale drug carrier works by caging therapeutic agents—in this case, drugs such as gabapentin and cyclosporine A—to carry them within the body. Once a caged drug has migrated through a patient’s circulatory system and made its way to the brain, doctors can beam near-infrared (NIR) light through the patient’s skull to energize the molecule and “open” the cage.

 

BrainProtect_V4

USC scientists have developed an experimental precision treatment for traumatic brain injury (TBI) that involves trapping therapeutic drugs in nanocage carriers before administering treatment. Near-infrared (NIR) light can safely penetrate the skull, and it can be used to “open” the nanocage to release drugs at the site of brain injury. (Image credit: Emily Louie)

 

The beauty of this approach is multifold. Caging the drug before releasing it at the site of injury minimizes the side effects that one would expect from delivering an active drug throughout the entire body. Moreover, because the brain’s barrier is weakest where it experienced the most trauma, higher concentrations of the drug will enter the brain precisely at the site of damage—thus circumventing the need for time-consuming imaging to locate the damage before proceeding with first-line treatment.

The researchers chose NIR frequency specifically for its ability to safely permeate human tissue without residual side effects, and they designed the nanocage itself to be biodegradable and nontoxic. This emerging intervention is still in its preclinical stages, but the researchers anticipate that it can be packaged as a portable intervention for first responders to immediately administer within a patient’s “golden hour.”

“I’m very hopeful for the impact this drug delivery tool could ultimately have on the millions of patients who experience TBIs each year,” said Mark Humayun, MD, PhD, director of the USC Ginsburg Institute for Biomedical Therapeutics, who is the study’s principal investigator. “A rapid intervention like this could significantly improve patient outcomes, and our team is excited to continue testing this approach to hopefully bring it to the clinic soon.”

Caroline Black, PhD, lead author on the study, says this research was made all the more meaningful because of her personal connection to TBI within her family. “My dad had a severe TBI when he was 17 and I’ve seen how the effects of secondary injury can persist decades after the initial trauma,” said Black, who is a USC-AbbVie postdoctoral fellow specializing in drug delivery sciences at the biopharmaceutical company AbbVie. “Our drug delivery tool has the potential to open new possibilities for rapid treatment of TBI, and I’m excited to see the impact it could have on improving patient outcomes.”

In addition to Humayun and Black, other researchers on the study include Caitlin M. DeAngelo, PhD, of the USC Department of Chemistry; Eugene Zhou and Isaac Asante, PhD, of the USC School of Pharmacy; Stan G. Louie, PharmD, of the USC School of Pharmacy and the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics; and Nicos A. Petasis, PhD, of the USC Department of Chemistry, the USC School of Pharmacy and the USC Ginsburg Institute.