However, a new Keck Medicine of USC study published today in eBioMedicine suggests that increasing omega-3 levels via supplements has little effect on brain health despite showing evidence that the nutrients directly reach the brain. 

The two-year, placebo-controlled, double-blinded study of older adults with an elevated risk of developing Alzheimer’s showed that high doses of omega-3s did not improve memory, cognitive function or brain cell loss in areas of the brain related to Alzheimer’s. 

“We all wish there was a silver bullet for preventing Alzheimer’s, but our findings showed that fish oil supplements do not appear to protect brain health,” said Hussein Naji Yassine, MD, director of the USC Center for Personalized Brain Health and lead investigator of the study. “While omega-3s play an important role in forming brain cell connections needed for cognition, our results do not support fish oil supplements as a preventive measure against Alzheimer’s.” 

How the study was conducted 

Researchers recruited 365 adults, ages 55 to 80 who rarely ate fish, which is rich in omega-3s, and who study authors considered at risk for Alzheimer’s. About half (47%) carried an APOE4 gene, the strongest genetic risk factor for late-onset Alzheimer’s. Participants were randomly chosen to receive either daily fish oil supplements or a placebo. The supplements contained 2,000 mg of docosahexaenoic acid (DHA), a key omega-3 involved in brain function. 

Researchers were first interested to learn whether the omega-3 in the supplement was able to reach the brain.  

They measured DHA levels in cerebrospinal fluid, which surrounds the brain, and found an average 17% increase of DHA levels in patients’ brains after six months, confirming the omega-3 reached its intended target. 

Next, researchers tested participants’ memory and cognitive abilities at the beginning of the study and again two years later. Study participants who took DHA supplements did no better on the tests than those who took a placebo. Brain scans also showed that supplements did not prevent shrinkage of the hippocampus, a brain region important for memory that is often used as a marker of brain aging and Alzheimer’s risk. 

Looking beyond supplements 

Now, Yassine and his team are focused on solving why omega-3 supplements can reach the brain but not affect brain health. Based on their previous research, they believe omega-3s may work better as a part of a Mediterranean-style diet, which is naturally rich in omega-3s and linked with lower Alzheimer’s risk, than in a standalone supplement. 

“We’re focused on better understanding how the brain processes omega-3s and whether factors, such as poor health, dietary pattern, genetic risk and age, may change the brain’s ability to effectively absorb and use omega-3s,” said Yassine. “We are working to develop medications that may help the brain better utilize these nutrients to preserve cognitive function.”  

Holistic lifestyle remains the best prevention  

While out of scope of the study, the researchers stress that overall healthy living — rather than relying on fish oil supplements alone —is the best way to protect brain health.  

“Staying healthy throughout life remains the most powerful tool we have for reducing Alzheimer’s risk, including regular exercise, quality sleep and a balanced diet,” said Yassine. “Living a healthy lifestyle is the brain’s equivalent of getting regular car maintenance and high-quality oil changes. The brain is more likely to lose greater function if health issues in other parts of the body go unaddressed, in the same way that car engines stop working if regular maintenance is skipped.” 

Other USC authors for the study include Lina D’Orazio, PhD, a clinical psychologist and neuropsychology specialist with Keck Medicine; Lon Schneider, PhD, a professor of psychiatry and behavioral sciences at the Keck School of Medicine of USC; Michael Harrington, MD, a professor of research neurology at the Keck School; and Meredith Braskie, PhD, an assistant professor of neurology at the Keck School. 

Parkinson’s disease is associated with reduced dopamine release in the brain. Dopamine is a neurotransmitter essential for movement, memory, mood and other functions. Research has shown that the tremors, stiffness, slow movement and other symptoms of Parkinson’s disease are caused by the progressive loss of dopamine-producing brain cells, disrupting the brain’s ability to regulate movement. 

Keck Medicine of USC is conducting an early phase clinical trial investigating the safety and effectiveness of implanting specialized stem cells into the brain that have been programmed to replace damaged brain cells and produce dopamine.  

“If the brain can once again produce normal levels of dopamine, Parkinson’s disease may be slowed down and motor function restored,” said Brian Lee, MD, PhD, a neurosurgeon with Keck Medicine and principal investigator of the study. 

Click here for seven warning signs of Parkinson’s disease

Unique stem cell therapy 

The therapy is a relatively new type of lab-generated stem cell called induced pluripotent stem cells (iPSCs). Unlike embryonic stem cells, iPCSs are adult cells, such as skin or blood cells, reprogrammed to a "blank slate" state capable of evolving into any type of cell. 

“We believe that these iPSCs can reliably mature into dopamine-producing brain cells, and offer the best chance of jump-starting the brain’s dopamine production,” said Xenos Mason, MD, a neurologist who specializes in Parkinson’s disease and other movement disorders with Keck Medicine and co-principal investigator of the study.  

During the procedure, Lee drills a small hole in the patient’s skull to access the brain, then precisely implants the stem cells into the basal ganglia, a part of the brain that controls movement, under the guidance of magnetic resonance imaging (MRI). 

After surgery, patients are monitored for 12-15 months for any changes in their Parkinson’s disease symptoms and for possible side effects including dyskinesia — excess movements — or infection. The doctors will continue to monitor the patients and their Parkinson’s disease symptoms for up to five years. 

“Our ultimate goal is to pioneer a technique that can repair patients’ motor function and offer them a better quality of life,” said Lee. 

Keck Medicine is one of three organizations in the United States participating in the clinical trial. The multisite study includes a total of 12 participants with moderate to moderate-severe Parkinson’s disease. 

This announcement is intended to share information about Keck Medicine’s research involvement and is not soliciting participants. 

Now, a novel clinical trial offers hope for patients with advanced “dry” age-related macular degeneration. Dry age-related macular degeneration is the most common form of the disease.

Researchers at the USC Roski Eye Institute, part of Keck Medicine of USC, are launching a phase 2b clinical trial examining if stem cells bioengineered to replace failing cells in the retina damaged by macular degeneration could restore eyesight. The cells are attached to an implant — an ultra-thin patch, thinner than a strand of hair — which holds the cells in place.

“We are hoping to determine if the stem-cell based retinal implant can not only stop the progression of dry age-related macular degeneration, but actually improve patients’ vision,” said Sun Young Lee, MD, PhD, a retinal surgeon with Keck Medicine and principal investigator of the Keck Medicine study site. “The findings could be groundbreaking because while there are a few treatments available that delay the progress of macular degeneration, there are none able to reverse the damage already done.”

The clinical trial follows early research conducted by USC Roski Eye Institute experts on a small patient population that showed the implant was well-tolerated, stayed put in the eye and was successfully absorbed into the tissue of the retina. Additionally, 27% of patients had some improved vision.

“The earlier phase of the clinical trial showed the treatment to be safe with the potential to benefit patients’ vision; this next phase will investigate whether the therapy can achieve clinically significant improvements in vision,” said Lee, who is also an associate professor of ophthalmology and physiology & neuroscience at the Keck School of Medicine of USC. 

Click here for five tips to help prevent macular degeneration.

How the retinal implant works

Approximately 20 million Americans live with age-related macular degeneration. This number also includes cases of wet macular degeneration, which is a less common but more serious form of the disease.

Age-related macular degeneration affects the eye’s macula, which is located in the center of the retina and is responsible for central vision. In advanced cases, the retinal pigment epithelium (RPE) cells, which line the macula and are key in helping the retina produce clear vision, become damaged or destroyed, which leads to vision loss.

The retinal implant used in the clinical trial is derived from embryonic stem cells grown into RPE cells in a lab. During an outpatient surgical procedure, Keck Medicine eye surgeons will implant a tiny layer of the lab-produced RPE cells into the retina.

“The study will explore if the lab-engineered implant will take over for the damaged cells, function as normal RPE cells would, and improve vision for patients who may currently have no other options for improvement,” said Rodrigo Antonio Brant Fernandes, MD, PhD, an ophthalmologist with Keck Medicine and the study surgeon. He is also an associate professor of clinical ophthalmology at the Keck School. 

Details of the clinical trial

Keck Medicine is one of five locations in the nation enrolling patients in the clinical trial. The study is masked — some of the enrolled participants will receive the implant, while others receive a simulated implant.

Eligible patients must be between ages 55-90 with advanced dry age-related macular degeneration and a diagnosis of geographic atrophy, meaning their RPE cells are damaged or not functioning.

Patients will be monitored for at least one year to determine how the implant is tolerated and for any changes in vision. The trial is hoping to enroll 24 patients.

Those interested in learning more about the trial can contact Mariana Edwards at mariana.edwards@med.usc.edu or Kimberly Rodriguez at kimberly.rodriguez2@med.usc.edu.

"The USC Roski Eye Institute is dedicated to furthering innovative treatments to help improve lives by restoring vision,” said Mark S. Humayun, MD, PhD, co-director of the USC Roski Eye Institute, director of the USC Ginsberg Institute for Biomedical Therapeutics and the Dennis and Michele Slivinski Chair in Macular Degeneration Research at the Keck School. “Stem cell-derived retinal implants may offer one of the greatest possibilities for helping patients with dry age-related macular degeneration and one day, may offer a cure.”

The study involved 140 patients from the IGNYTE clinical trial, which included Keck Medicine and other sites worldwide. These patients had advanced melanoma that did not respond or stopped responding to immunotherapy, which uses the body’s own immune system to fight cancer.

Patients were treated with a genetically modified HSV-1 in combination with an immunotherapy (nivolumab). By the end of the clinical trial, one-third of the participants had their tumors shrink by at least 30%, and nearly one out of six patients had tumors completely disappear.

“These findings are very encouraging because melanoma is the fifth most common cancer for adults, and about half of all advanced melanoma cases cannot be managed with currently available immunotherapy treatments,” said Gino Kim In, MD, a medical oncologist with Keck Medicine and principal investigator at the Keck Medicine clinical trial site. Dr. In is also a member of the IGNYTE trial steering committee and one of the lead investigators on the trial. “The survival rate of untreatable advanced melanoma is only a few years, so this new therapy offers hope to patients who may have run out of options to fight the cancer.”

A novel class of drugs to fight cancer

The genetically modified HSV-1 evaluated in the study, RP1, is one of a relatively new, innovative class of cancer immunotherapy drugs known as oncolytic viruses that are designed to target and destroy cancer tumors while generating an anti-tumor immune response throughout the entire body. RP1 does not cause herpes.

In January 2025, the U.S. Food and Drug Administration granted priority review to RP1 with nivolumab for patients with advanced melanoma whose cancer had not responded to prior immunotherapy.

When injected into a tumor, RP1 replicates, killing off the cancer cells while leaving healthy cells unharmed. Additionally, RP1 stimulates the body’s white blood cells to seek out and destroy any other cancer cells in the body.

The second cancer drug used in the study, nivolumab, is a standard immunotherapy treatment in fighting advanced melanoma and other cancers that have spread through the body. Researchers theorized that nivolumab, which works by using the body’s own immune system to fight and destroy cancer cells, would enhance the potential effect of RP1.

How the treatment was administered

Patients admitted into the study had already been treated with minimal success by one or more immunotherapy therapies and had to have more than one tumor that could be injected with RP1. Some tumors were considered “superficial” — meaning visible on the skin, or just below the skin’s surface — and some were located deeper in the body, such as in the liver or lungs. Researchers injected both superficial and deep tumors with RP1.

Encouraging Findings  

During the clinical trial, patients were given a combined therapy of RP1 and nivolumab every two weeks for up to eight cycles. If patients responded to the treatment, they continued on nivolumab alone every four weeks for up to 30 cycles (or two years).

Researchers measured both treated tumors and untreated tumors. They discovered that not only did injected tumor size shrink in one third of the patients by 30%, but that patients’ uninjected tumors also shrank or even disappeared, just as frequently and as deeply.

“This result suggests that RPI is effective in targeting cancer throughout the entire body and not just the injected tumor, which expands the potential effectiveness of the drug because some tumors may be more difficult or impossible to reach,” said Dr. In, who is also a member of USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC.

The study also found that RP1 was well-tolerated and had a favorable safety outcome.

While it is too soon to tell if the positive outcomes remain permanent, Dr. In is optimistic about the future of RP1 therapy. “I believe that oncolytic viruses will open up an important new approach to fighting cancer in some patients in the near future,” he said.

Other clinical trial researchers include Phillip M. Cheng, MD and Ali Rastegarpour, MD, diagnostic radiologists with Keck Medicine.

Phase 3 clinical trial now open

Phase 1-2 of the IGNYTE clinical trial examined the safety, side effects, best dosing and effectiveness of administering RP1 along with nivolumab on a limited patient population. Dr. In and his fellow researchers have launched the phase 3 trial, known as IGNYTE-3, to confirm their findings in a global population of more than 400 participants.

Keck Medicine will again be one of the sites of the clinical trial, with Dr. In heading up the site. Patients interested in participating can contact Sandy Tran at sandy.tran@med.usc.edu.

Replimune, a manufacturer of RP1 and other oncolytic immunotherapies, is the sponsor of the IGNYTE clinical trial

Disclosure: In Dr. In’s role as a member of the steering committee for the IGNYTE clinical trial, he has served on advisory boards for the sponsoring company and received honoraria.

LOS ANGELES — Steam eliminates wrinkles and germs, but can it destroy cancer cells too?  

Keck Medicine of USC is participating in a national, multisite clinical trial examining if a water vapor system that uses small, targeted amounts of steam to kill cancer cells is a safe and effective treatment for prostate cancer. 

Researchers hope that steam may offer patients a less invasive way of controlling or curing cancer than currently exists.  

“The most common therapies for prostate cancer often cause life-altering side effects, and we are investigating if this new treatment may not only treat the cancer, but offer our patients overall better quality-of-life outcomes,” said Andre Abreu, MD, a Keck Medicine urologist and lead investigator of the Keck Medicine clinical trial site. Abreu also leads focal therapy and artificial intelligence efforts for prostate cancer with USC Urology. 

Who may benefit from the trial   

The clinical trial is designed for patients with intermediate-risk prostate cancer, meaning that the tumor is localized in the prostate gland and has not spread to other organs. This type of cancer accounts for approximately one-third of all localized prostate cancers, according to Abreu. 

Some patients with prostate cancer may not need any treatment if the cancer is small enough and slow growing. However, when treatment is necessary, traditionally, physicians have treated patients with either surgery or radiation.  

These techniques are generally effective in treating the cancer, however, there can be side effects. The prostate is located in between the bladder, the urethra (a duct that transports urine from the bladder) and the rectum. It is surrounded by numerous nerves responsible for penile erections and the muscle that controls urine flow, the urinary sphincter. During surgery or radiation, there is a risk of injuring healthy tissue along with the cancer and damaging the delicate structures that lie next to the prostate.  

The most common side effects of surgery and radiation are impotence, urinary incontinency and bowel dysfunction. 

“While patients are happy to be free of cancer, the costs of the cure are very high,” said Abreu. “There is a growing amount of literature in the field suggesting that select patients could benefit from a procedure with fewer risks that allows them to maintain their quality of life after cancer.” 

How steam might fight cancer 

Heat is one therapy to help damage and kill cancer cells, according to the National Cancer Institute. Steam offers a targeted way to deliver heat into the body, according to Abreu.  

Before the procedure, physicians use magnetic resonance imaging (MRI) to locate the tumor cells in the patient’s prostate. During the procedure, doctors use an ultrasound and prostate mapping to guide a thin catheter through the patient’s urethra and into the area of the prostate where the tumor is located.  

Once the catheter is positioned, a fine needle is deployed in the tumor. Doctors then release a quick, targeted 10-second burst of steam from the needle, and more bursts as needed, to destroy the tumor.  

“This procedure is thought to be much gentler on the body than traditional therapies and is designed to target the cancerous tissue within the prostate,” said Abreu. “We are exploring if steam may be effective at destroying cancer cells without damaging the surrounding organs.”  

Another potential advantage to the investigational therapy is that unlike surgery, which requires an overnight stay in the hospital, the water vapor therapy is an outpatient procedure. And unlike radiation, which usually involves multiple sessions, the water vapor therapy is designed to work using only one application. 

Clinical trial details  

The clinical trial is being conducted at up to 30 hospitals and health centers across the nation. So far, more than 180 procedures have been completed. 

Keck Hospital of USC is the only Los Angeles area site participating in the study. Patients’ post-treatment cancer outcomes will be followed for five years.  

The study is sponsored by Francis Medical, Inc., a privately held medical company that developed the device being used, the Vanquish^® Water Vapor Ablation System.  

The water vapor ablation system is one of several minimally invasive treatments for prostate cancer either already in use or being developed within the field of urology.  

“Over the next decade or so, we hope to see innovative therapies revolutionize how we help patients become cancer-free while maintaining their quality of life,” said Abreu.  

Dr. Abreu declares no conflict of interest with the sponsor.

Immunotherapy, medicines that use the body’s immune system to eliminate or control cancer cells, are effective for many cancer patients, but are currently only administered intravenously (into the vein) in a doctor’s office or hospital. 

The study will examine if a new formulation of atezolizumab, an immunotherapy approved for treating certain types of non-small cell lung cancer, can instead be safely and effectively administered subcutaneously, meaning it is injected under the patient’s skin, by a nurse at the patient’s home, along with telemedicine appointments and remote monitoring through wearable trackers.  

This will be the first clinical trial to test at-home administration of subcutaneous immunotherapy and could potentially lay the foundation for the future of at-home cancer care. 

“Many types of drugs are now being delivered subcutaneously at home for several conditions, and we hypothesize that this method of drug delivery can also be successful for cancer patients,” said Jorge Nieva, MD, a medical oncologist and lung cancer specialist with Keck Medicine, a member of USC Norris Comprehensive Cancer Center and lead investigator of the clinical trial. “Additionally, since COVID-19, we’ve learned that physicians have the digital tools to provide patients with excellent remote care.” 

The benefits of at-home treatment 

Lung cancer is the second most diagnosed cancer in the world and the leading cause of cancer deaths for both men and women worldwide. Non-small cell lung cancer accounts for 81% of all lung cancer cases in the United States.  

Immunotherapy is a relatively new treatment option that has been approved to treat many cancer types both on its own or in combination with other therapies, such as radiation and chemotherapy.  

Nieva believes that moving immunotherapy from a medical setting to the home will benefit patients. Patients will save time and energy traveling to a clinic or doctor’s office, which can be especially difficult for those who are very sick, and they may feel more relaxed in their own homes. This could also potentially expand access to cancer treatment to patients who live in more remote areas or lack reliable access to transportation. 

Delivering the drug under the skin rather than through an intravenous line (IV) has advantages as well.  

“The procedure is easier and faster to administer and less likely to cause infection or complications, and patients avoid the potential discomfort of being stuck with a needle several times in the attempt to find a suitable vein for the IV,” said Nieva.  

Nieva was motivated to research at-home cancer treatments during the COVID-19 pandemic when a patient who was afraid of catching the virus died after he stopped going into the hospital for his cancer treatments. 

“I realized we had to change the delivery of cancer care,” said Nieva.  

Clinical trial will use an immunotherapy consisting of monoclonal antibodies 

The drug used in the clinical trial, atezolizumab, consists of a monoclonal antibody, a man-made protein that triggers the immune system to attack cancer cells. It was approved by the Food and Drug Administration in 2016 for late-stage lung cancer and more recently in 2021, for early stage, non-small cell lung cancer. 

Investigators aim to enroll 37 patients with non-small cell lung cancer who are deemed eligible to receive immunotherapy as treatment. Patients will receive treatments administered by a nurse who will visit their home every three weeks for one to two years.  

Additionally, Nieva and his colleagues will use the latest digital tools to track patients’ vital signs, physical activity and other markers of health remotely and monitor patients with telehealth visits.  

The study will not only examine the feasibility of home administration of the medication, but how well patients comply with the program and how satisfied they are with being treated remotely and through telehealth appointments. 

Nieva hopes that the clinical trial will not only benefit patients with non-small cell lung cancer, but other cancer patients as well. 

“Increasingly, health care is moving in a direction where instead of patients going to us for services, we are able to come to them, increasing access to care and potentially addressing existing health care disparities,” said Nieva. “If this study can show that at-home cancer immunotherapy is safe and feasible for non-small cell lung cancer, it will open the door for more home treatments for other types of cancers in the future.” 

To learn more about the criteria to participate in the clinical trial, click here. Those who are interested in participating in the trial may contact Sandy Tran at (323) 865-3935 or sandy.tran@med.usc.edu.  

The sponsors of the clinical trial are the National Cancer Institute (NCI), grant number ML43326, and Genentech, Inc. 

The study will investigate if chemotherapy followed by a novel type of surgery to remove the cancer is a safe and effective option for patients with locally advanced pancreatic cancer, meaning that the cancer has not spread to other organs, but has grown into or close to nearby blood vessels that surround the pancreas. 

“Usually, these types of tumors cannot be safely removed with surgery because of the risk of damaging the blood vessels, which supply blood to the stomach, liver and other abdominal organs. However, due to recent advancements by Keck Medicine surgeons, we believe that patients with locally advanced cancer can be candidates for successful surgery, which could significantly improve outcomes,” said Steven Grossman, MD, PhD, co-lead investigator of the study. Grossman is a medical oncologist with Keck Medicine and deputy director for cancer services at USC Norris Comprehensive Cancer Center, part of Keck Medicine.  

The challenge of treating pancreatic cancer 

Pancreatic cancer accounts for only about 3% of cancers in the United States, but it is one of the deadliest. People usually have no symptoms until the cancer has become very large or metastasized throughout the body, so the cancer is caught late, and patients have poor prognoses.  

Only 13% of pancreatic cancer patients survive five or more years after diagnosis.  

The life expectancy of patients with locally advanced pancreatic cancer, which accounts for one third of all pancreatic cancer cases, has historically been about one year.  

For most forms of cancer, surgery is considered the most effective treatment for localized tumors that have not spread to other areas of the body. However, surgery has traditionally not been offered for tumors involving the blood vessels near the pancreas because if the blood vessels were to become damaged during the procedure, and the blood flow to organs interrupted, it could result in serious side effects or death.  

Therefore, typically the only treatment option for patients with locally advanced cancer is chemotherapy and/or radiation, both of which have limited effectiveness killing pancreatic cancer cells.  

“The situation is frustrating because research shows that in the rare cases where locally advanced tumors were safely removed, the progression of the disease was slowed and the patient’s length of survival on average increased from one year to 28 months, more than doubling life expectancy,” said Sandra Algaze, MD, a medical oncologist with Keck Medicine, a member of USC Norris and one of the study’s investigators. “Surgery, therefore, appears to strongly benefit a patient’s survival rate, which is why the medical field has been eager for a surgical solution.”  

How new surgical advances can benefit patients  

The clinical trial will use surgical protocols pioneered by Keck Medicine surgeons to safely remove locally advanced pancreatic tumors attached to arteries. The surgical team will be led by study co-lead investigator Yuri Genyk, MD, a hepatobiliary and pancreatic surgeon with Keck Medicine who is an expert in vascular reconstruction, which is the removal and reconstruction of blood vessels. Genyk has already successfully removed about 30 pancreatic tumors that were attached to adjacent arteries.  

“While this surgery is very complex, we have the skills and expertise to execute it and train other skilled surgeons in the procedure. If the trial results are positive, we envision that the technique could become the gold standard for how this stage of pancreatic cancer is treated in the future,” said Genyk. 

Patients in the clinical trial will first undergo chemotherapy to attempt to shrink the tumor. Two to eight weeks after completing chemotherapy, they will undergo a laparoscopic evaluation to determine the position and size of the tumor before the tumor is surgically removed and involved blood vessels are removed and reconstructed. 

Patients will be followed every three months for the first year post-surgery and then every six months for two years after that.  

The clinical trial will also examine if certain biomarkers, such as the tumor’s DNA, as well as a patient’s demographic factors such as age and gender, play a role in patient outcomes. 

The study hopes to enroll 20 patients with locally advanced pancreatic cancer who have evidence of arterial involvement by their tumors. The surgeries will be performed at Keck Hospital of USC.  

“Pancreatic cancer is a devastating diagnosis, and Keck Medicine is committed to finding better solutions for the disease,” said Grossman. “Anything we can do to improve patients’ quality of life and extend life expectancy will be a huge milestone that could benefit countless patients and their loved ones.” 

Those interested in participating in the study can contact: Charlean Ketchens, RN, at (323) 865-3035 or ketchens_c@med.usc.edu. 

Urologists with Keck Medicine of USC have launched a clinical trial to perform the world’s first human bladder transplant.

The trial is actively screening potential participants for this first-ever type of transplantation.

During the procedure, the patient’s diseased bladder will be removed and replaced with a healthy bladder from a deceased donor.

“Transplantation is a lifesaving treatment option for conditions affecting many major organs, and transplanting a bladder could be a historic step in improving lives,” said Inderbir Gill, MD, founding executive director for USC Urology, part of Keck Medicine. Gill is also the principal investigator of the clinical trial and leading the transplantation efforts. “We could be on the verge of a medical advance that has the potential to revolutionize how we treat terminally compromised bladders.”

Hundreds of millions of people around the globe experience varying degrees of bladder disease and dysfunction. Some patients with these conditions may require a bladder reconstruction, a surgical procedure wherein the bladder is removed, and a new bladder is made from the patient’s own intestines. However, the procedure carries a high risk of early and delayed adverse side effects, and not every patient is a candidate for this surgery.

“The intention of this clinical trial is to develop a new treatment option for a certain subset of patients with debilitating bladder conditions that can severely hamper quality of life and ultimately, even shorten life,” said Nima Nassiri, MD, urologic surgeon and researcher with the Keck School of Medicine of USC and Gill’s collaborator on the clinical trial. “We have worked diligently to expand the boundaries of what is considered possible for severely compromised patients who traditionally have had few options.”

Bladder transplants have not been done previously, in part because of the complicated vascular structure of the pelvic area and the technical complexity of the procedure. Gill, Nassiri and their colleagues have spent the past few years developing and practicing numerous research procedures to prepare for the first-in-human bladder transplant, which will be done completely using robotic surgery.

Robotic surgery is an advanced form of minimally invasive surgery in which surgeons use a high-definition, three-dimensional camera to guide a robot to perform surgery using smaller, more precise incisions with more dexterity than is possible using hand-held surgical tools.

Under Gill’s direction, USC Urology has established itself as a pioneer and world leader in robotic, minimally invasive techniques for kidney, bladder and prostate cancer surgery, and achieved important milestones leveraging machine learning and artificial intelligence to optimize patient outcomes.

Keck Medicine’s USC Transplant Institute, which has a robust and nationally recognized kidney, liver, heart and lung transplant program, further provided Keck Medicine with the needed resources and skills to pioneer the first bladder transplant.

As part of the research and development stage, Gill, Nassiri and colleagues successfully completed many practice transplantation surgeries, including the first-ever robotic bladder retrievals and successful robotic transplantations in five recently deceased donors with cardiac function maintained on ventilator support.

The procurement, surgery and post-surgical monitoring during transplantation were aligned with current clinical and research standards. OneLegacy Foundation, an organ procurement organization serving Southern California, provided clinical trial funding and, with the generous agreement of donor families, enabled bladder donations that made the trial possible.

Nassiri and Gill are presenting their surgical research update April 30 at the annual meeting of the American Urologic Association, the world’s leading association for urology professionals.

Gill, in addition to directing USC Urology, is chairman and Distinguished Professor of the Catherine and Joseph Aresty Department of Urology and the Shirley & Donald Skinner Chair in Urologic Oncologic Surgery at the Keck School.

Photo caption: The Keck Medicine of USC surgical team evaluates the integrity of a bladder during the research and development stage of bladder transplantation.

Seminoma is a slow-growing form of testicular cancer that if untreated, typically metastasizes (spreads) to lymph nodes in an area behind the abdomen lining called the retroperitoneum. The standard treatment for patients at this stage is chemotherapy and radiation to shrink and kill the cancerous lymph nodes.  

While effective, chemotherapy and radiation are associated with long-term side effects, such as cardiovascular disease and secondary cancers, that adversely affect a patient’s quality of life.

Now, however, the results of a multi-institutional clinical trial recently published in the Journal of Clinical Oncology show that surgically removing the affected lymph nodes in the retroperitoneum is an effective alternative to chemotherapy and radiation with fewer long-term side effects.

“We found that the majority of participants in the study were cured with surgery alone, avoiding the toxicities associated with traditional therapies. We are confident that surgery for this disease state will be included into treatment guidelines in the near future,” said Sia Daneshmand, MD, a urologic oncologist with Keck Medicine of USC and lead investigator of the clinical trial.  

Daneshmand is also a member of USC Norris Comprehensive Cancer Center, part of Keck Medicine.

Testicular cancer is generally a treatable cancer that most commonly affects men ages 15-35. When testicular cancer only spreads to the retroperitoneum, it is classified as early metastatic or stage 2 seminoma.

The procedure to remove lymph nodes from the retroperitoneum — known as a retroperitoneal lymphadenopathy — is an established treatment for metastatic testicular cancer when chemotherapy fails to eradicate all affected lymph nodes. However, surgery has not traditionally been considered a viable stand-alone treatment for early metastatic seminoma.

The national study enrolled 55 patients across 12 institutions to investigate if surgery could replace chemotherapy and radiation as an effective treatment, thereby sparing patients the long-term risks associated with the two traditional therapies.

Study participants had previously undergone surgery to remove the testicle(s) where the original cancer occurred, and their cancer had progressed no further than to the retroperitoneum. Once enrolled, the patients underwent a retroperitoneal lymphadenopathy by certified surgeons at participating institutions around the country and one site in Canada.

Keck Hospital of USC performed 15 of the surgeries. Most of the Keck Medicine patients were able to go home 24 hours after surgery with minimal or no complications, according to Daneshmand.

Daneshmand and his colleagues found that 81% of the patients demonstrated a two-year recurrence-free survival rate. The 20% who did experience recurrence of the cancer were successfully treated with either chemotherapy or additional surgery for an overall survival rate of 100%.

“A 100% survival suggests that a cure can still be achieved even in patients who experience recurrence after the surgery,” said Daneshmand.

Daneshmand acknowledges that not all hospitals or medical centers have the expertise or resources to successfully complete retroperitoneal lymphadenopathy. He advises patients to look for an academic medical center to discuss the possibility of surgery over traditional therapies.

“Early metastatic seminoma has a very high survival rate; however if treated with chemotherapy and radiation, the cure can come at a high cost,” he said. “Surgery gives patients both the opportunity to be cured and experience a high quality of life post-cancer.”

Anne Schuckman, MD, a urologic oncologist with Keck Medicine, was also an investigator in the clinical trial.

Diabetes is a chronic condition where the body does not produce or effectively use insulin. A lack of insulin leads to raised blood glucose (sugar) levels, which can cause heart disease and stroke, kidney disease, nerve damage and other severe complications.

Keck Medicine of USC has launched a Phase 2 clinical trial investigating the effectiveness of a new outpatient, nonsurgical endoscopic procedure in stabilizing blood glucose levels for patients. 

“Currently, the only treatment for diabetes not managed with lifestyle changes are oral medications or, in the case of advanced disease, insulin injections, both of which can be costly or have side effects,” said Luke Putnam, MD, lead investigator of the clinical trial and a gastrointestinal surgeon with Keck Medicine. “If this therapy is proven effective, it could eliminate the need for medication or insulin, or potentially prevent disease progression so it does not lead to organ failure and other debilitating conditions.”

This innovative procedure is designed for patients before they require insulin and targets the duodenum, the first part of the small intestine that works with the pancreas to regulate insulin and blood glucose levels.

Recent data suggests the duodenum plays an important role in glucose regulation, and in patients with Type 2 diabetes, the cells lining the duodenum become damaged.

The clinical trial is testing a device inserted via an endoscope into the duodenum that ablates (removes) the poorly functioning cells through precise, controlled electrical pulses.

The study researchers hypothesize that ablating the damaged cells will promote the regrowth of healthy cells, which will better regulate blood glucose levels.

The procedure takes about an hour and is done under general anesthetic. Patients are discharged the same day and can continue normal activities a few days later.

“Previous studies have shown that ablation of cells in the duodenum is effective in controlling blood sugar levels, so we are optimistic this study will produce successful results,” said Putnam.

Clinical trial participant Mark Canning, a 60-year-old Los Angeles resident who was diagnosed with Type 2 diabetes in 2015, is seeing progress controlling his blood glucose since undergoing the procedure in January. “My blood sugar levels are falling, and I am feeling very encouraged,” he said.

The clinical trial is currently enrolling new patients. To qualify for the study, patients must be between the ages of 22-65 and have a history of Type 2 diabetes between three to 10 years. Participants can be on oral medications but not insulin.

Those interested in participating in the study should contact Christian Romero at christian.romero@med.usc.edu.

John Lipham, MD*, a gastrointestinal surgeon with Keck Medicine, is co-investigator of the study.

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Download b-roll below of clinical trial participant Mark Canning undergoing an outpatient, nonsurgical endoscopic procedure that may help patients stabilize blood glucose levels.

* Lipham has a financial interest in the company sponsoring this study. He is a consultant for the sponsoring company, Endogenex, Inc. The nature of this conflict and the management of the conflict of interest have been reviewed by the USC Conflict of Interest Review Committee.

Keck Medicine of USC is enrolling individuals in an international phase 3 clinical trial to examine the safety and effectiveness of deep brain stimulation to treat Alzheimer’s. The study uses electrical impulses to stimulate the region of the brain known as the fornix, which is associated with memory and learning.

“Deep brain stimulation has successfully treated conditions such as Parkinson’s disease by improving motor skills, and we are now investigating if this therapy can stabilize or improve cognitive function,” says Darrin Lee, MD, PhD, a neurosurgeon with Keck Medicine of USC and the site’s principal investigator of the study. “Based on the results of earlier phases of this clinical trial, the treatment offers a potential benefit for patients with mild Alzheimer’s.”

This randomized, double-blind study will last four years. Subjects will first take a standardized assessment test for Alzheimer’s to be used as a baseline measure of cognitive ability throughout the study.

Next, researchers will implant electrodes into subjects’ brains that connect to a battery pack, similar to a heart pacemaker, placed underneath the collarbone.

For the first year of the study, subjects will be given either low-frequency stimulation to the brain, high-frequency stimulation or a placebo — no stimulation.

“For those with Alzheimer’s disease, certain parts of the brain become atrophied,” Lee says. “We are testing to see if stimulating the brain’s fornix can reawaken brain activity in this area and stop the progression of the disease.”

During the first year, subjects will be given subsequent cognitive tests to check if their memory or learning skills have held steady or improved. At the end of the year, study researchers will examine data to determine which level of stimulation had the most impact on these skills.

For the next three years of the trial, all subjects in the study will receive what researchers have determined is the optimal frequency of deep brain stimulation, even those originally receiving the placebo. Patients will continue to be given cognitive assessments throughout the four-year period.

To qualify for the trial, patients must be 65 or older, have been diagnosed with mild Alzheimer’s and take Alzheimer’s medication, and have a caregiver or family member who can accompany them to doctor visits.

The clinical trial involves approximately 200 patients at some 20 sites in the United States, Canada and Germany. Keck Medicine plans to enroll 8-15 patients.

Those interested in enrolling in the clinical trial with Keck Medicine can contact Amanda Romano at amanda.romano@med.usc.edu or 213-393-5640.

Keck Medicine co-investigators of the trial include psychiatrist Carlos Manuel Figueroa, MD, and neurologist Elizabeth Joe, MD.

Deep brain stimulation has been approved by the U.S. Food and Drug Administration since 1997 and has proven to be safe.

The trial is sponsored by Functional Neuromodulation, Inc.

Learn more about the clinical trial here.

“Current wearable low vision technologies using virtual reality are limited and can be difficult to use or require patients to undergo extensive training,” said Mark Humayun, MD, PhD, director of the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics, co-director of the USC Roski Eye Institute and University Professor of Ophthalmology at the Keck School.

“Using a different approach — employing assistive technology to enhance, not replace, natural senses — our team adapted AR glasses that project bright colors onto patients’ retinas, corresponding to nearby obstacles,” Humayun said.

Patients with retinitis pigmentosa wore adapted AR glasses as they navigated through an obstacle course based on a U.S. Food and Drug Administration–validated functional test. Using video of each test, researchers recorded the number of times patients collided with obstacles, as well as the time taken to complete the course. Patients averaged 50% fewer collisions with the adapted AR glasses.

Patients also were asked to grasp a wooden peg against a black background — located behind four other wooden pegs — without touching the front items. Patients demonstrated a 70% increase in grasp performance with the AR glasses.

“Patients with retinitis pigmentosa have decreased peripheral vision and trouble seeing in low light, which makes it difficult to identify obstacles and grasp objects. They often require mobility aids to navigate, especially in dark environments,” said Anastasios N. Angelopoulos, study project lead in Humayun’s research laboratory at the Keck School.

“Through the use of AR, we aim to improve the quality of life for low vision patients by increasing their confidence in performing basic tasks, ultimately allowing them to live more independent lives,” Angelopoulos said.
 
How the AR system works
The AR system overlays objects within a 6-foot wireframe with four bright, distinct colors. In doing so, the glasses provide visual color cues that help people with constricted peripheral vision interpret complex environments, such as avoiding obstacles in dimly lit environments.

To accomplish this, researchers used a process called simultaneous location and mapping, allowing the AR glasses to fully render the 3-D structure of a room in real time. The glasses then translated this information into a semitransparent colored visual overlay, which highlighted potential obstacles with bright colors to help patients with spatial understanding and depth perception. This technology can work on commercially available devices.

According to Humayun, while major cost and technical issues remain, this type of assistive technology could eventually become more practical for everyday use in the near future.

— Wendy Wolfson

Clinical trials provide researchers with insight into how people are likely to respond to medical interventions, including surgery. Factors such as age, weight, genetics, ethnic origin and geographic location all play a role in how a person may react to different treatments. For that reason, representation of diverse patient populations in clinical trials enables researchers to better address public health concerns.

“Nearly half of Los Angeles residents are Hispanic, making the Keck School uniquely positioned to recruit a large, underrepresented population in cardiac surgery trials,” said principal investigator Michael Bowdish, MD, MS, associate professor of surgery and preventive medicine at the Keck School. “By increasing patient diversity in cardiac surgery clinical trials, we are better suited to address cardiovascular disease, the No. 1 cause of mortality in the United States.”

The Keck School, through relationships with the Los Angeles County Department of Health Services, will recruit potential patients from areas with a large Hispanic presence, according to Bowdish. Potential patients also will be identified through the Southern California Clinical and Translational Science Institute (SC CTSI), which provides outreach and education to more than 30 predominantly Hispanic community health organizations in Los Angeles.

“Addressing the cardiovascular needs of our community is top priority,” said Vaughn A. Starnes, MD, chair and Distinguished Professor of Surgery and H. Russell Smith Foundation Chair for Stem Cell and Cardiovascular Thoracic Research at the Keck School. “This prestigious award provides us with valuable resources to discover novel and innovative therapies to improve the health of our Los Angeles community and beyond.”
The Keck School will collaborate with Saint Luke's Mid America Heart Institute in Kansas City, Missouri, as Linked Clinical Research Centers. This expands the patient pool for gathering and assessing data, enabling researchers to achieve stronger and more definitive research results, according to Bowdish.

In addition, the implementation science training program, under the leadership of Cecilia Patino-Sutton, MD, PhD, MEd, associate professor of preventive medicine at the Keck School, will explore novel ways to translate findings from clinical research in cardiac surgery into clinical practice. The program also will leverage collaborative relationships between the Keck School, SC CTSI, the USC Gehr Family Center for Health Systems Science, and the USC Leonard D. Schaeffer Center for Health Policy and Economics, as well as the Mid America Heart Institute Cardiovascular Research Fellowship.

Keck Medicine of USC has been an active member of the CTSN since 2010. The CTSN includes more than 40 major academic medical centers across the United States and Canada, and more than 20 hospitals in Europe.

The treatment, which consists of a layer of human embryonic stem cell–derived retinal pigment epithelium cells on an ultrathin supportive structure, was implanted in the retina of four patients by a USC Roski Eye Institute surgeon. The patients were followed for up to one year to assess its safety. There were no severe adverse events related to the implant or the surgical procedure, indicating that the treatment was well-tolerated. There was also evidence that the implant integrated with the patients’ retinal tissue, which is essential for the treatment to be able to improve visual function.

This is the first human trial of this novel stem cell–based implant, which is designed to replace a single-cell layer that degenerates in patients with dry age-related macular degeneration,” says lead author and surgeon for the study Amir H. Kashani, MD, PhD, assistant professor of clinical ophthalmology at the Keck School of Medicine of USC. “This implant has the potential to stop the progression of the disease or even improve patients’ vision. Proving its safety in humans is the first step in accomplishing that goal.”

A scanning electron microscope image of retinal pigment epithelial cells derived from stem cells.(Photo/USC Roski Eye Institute)

Dry age-related macular degeneration is the most common type of age-related macular degeneration. Over time, it can lead to loss of central vision, which can diminish people’s ability to perform daily tasks like reading, writing, driving and seeing faces. Age-related macular degeneration affects approximately 1.7 million Americans and is projected to rise to almost 3 million by 2020. It is a leading cause of severe visual impairment in adults older than 65.

As part of the study, the research team also performed a preliminary assessment of the therapy’s efficacy. One patient had improvement in visual acuity, which was measured by how many letters they could read on an eye chart, and two patients had gains in visual function, which was measured by how well they could use the area of the retina treated by the implant. None of the patients showed evidence of progression in vision loss.

“Our study shows that this unique stem cell–based retinal implant thus far is well-tolerated, and preliminary results suggest it may help people with advanced dry age-related macular degeneration,” says coauthor and lead inventor of the implant Mark S. Humayun, MD, PhD, director of the USC Institute for Biomedical Therapeutics, co-director of the USC Roski Eye Institute, affiliate principal investigator with the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC and University Professor of Ophthalmology at the Keck School. “CIRM has provided a conducive environment for stem cell research at the USC Roski Eye Institute and the Keck School of Medicine by providing funding for our clinical trial, along with a generous gift to the Eli and Edythe Broad Center for Regenerative Medicine.”

Humayun, David R. Hinton, MD, professor of pathology at the Keck School, and Dennis O. Clegg, PhD, University of California, Santa Barbara Wilcox Family Chair in BioMedicine and co-director of the campus’ Center for Stem Cell Biology and Engineering, co-invented the implant.
Collaborating institutions for the study include Regenerative Patch Technologies LLC, which also contributed to the funding of the study, as well as Camtek LLC, the California Institute of Technology, Retina Vitreous Associates Medical Group, California Retina Consultants, Atlantis Eyecare, City of Hope, University of California, Santa Barbara and Denney Research Center. Additional sources of funding for the study include Lori Mars gift, William K. Bowes Foundation, Vermont Community Foundation, Breaux Foundation, Wilcox Family Foundation and Research to Prevent Blindness.

For more information about the study, visit https://clinicaltrials.gov/ct2/show/NCT02590692?term=nct02590692&rank=1. To participate in the study, please call (323) 442-6335.

— Erica Rheinschild

One of these potential therapies treats the lesions associated with cervical dysplasia and vulvar dysplasia, conditions in which abnormal cells grow along the lining of the cervix or vulva. These conditions are strongly associated with human papillomavirus (HPV) infection and carry a high risk of becoming cancer when left untreated. Additionally, current methods for treating cervical and vulvar dysplasia can address the lesions but not the underlying viral infection, leaving these women at a lifelong increased risk for cervical or vulvar cancer. The investigational treatment involves an injection directly into the lesions to boost the patient’s immune response against HPV and hopefully help the patient clear the HPV from her body.

“Our hope is that this method will improve a patient’s overall immune response to HPV,” said Lynda Roman, MD, associate professor of obstetrics and gynecology and division chief of gynecologic oncology at the Keck School of Medicine of USC. Roman is also the principal investigator of the study. “Many women are infected with HPV but do not develop cervical or vulvar dysplasia, and we suspect that improving the body’s immune response to the virus is the key to halting the development of cervical and vulvar cancer.”

The second trial examines the efficacy of an immunotherapy for women with advanced or recurrent cervical cancer for whom chemotherapy and radiation has been ineffective. Currently, there are few viable treatment options for this subset of cervical cancer patients. The treatment involves T-cell therapy, a promising new approach, combined with chemotherapy to regulate the immune system. The clinical trial is supported by the National Cancer Institute, where the initial trial showing some success with this approach was done.

“If successful, this treatment could change the standard of care for women with advanced cervical cancer and potentially save lives,” said Roman, who is the principal investigator for this trial, as well. “Clinical trials are the method through which we push cancer treatment forward, and we are proud to be a part of this effort.”

Those interested in participating in either of these trials can visit clinicaltrials.keckmedicine.org for more information.

The American Cancer Society estimates that more than 13,200 women will be diagnosed with cervical cancer this year and that more than 4,000 women will die from the disease. The mortality rate has dropped significantly over the past few years due to improved screening, but populations with low access to gynecologic care are still very much at risk for the disease.

— Mary Dacuma