Neurogenic bladder, also called neurogenic lower urinary tract dysfunction, often occurs after a spinal cord injury. The spinal cord helps coordinate bladder storage and voiding. The neurogenic bladder that occurs after a spinal cord injury can lead to discoordination of normal bladder function, resulting in involuntary bladder muscle contractions which can cause overactive bladder symptoms like frequency, urgency, and incontinence, and can even lead to urinary tract infections and permanent kidney injury.

The therapy is a nonmultiplying gene therapy vector, or transporter, which is a modified form of the herpes virus. This vector carries the gene encoding the active part of botulinum toxin, which it will make in the spinal cord to block the sensory nerve signals that result in involuntary bladder contractions. The therapy is named EG110A by its developer EG 427, a biotechnology company.

“They have modified the herpes virus, which affects nerves, so that it is not virulent and does not multiply, and are relying on its innate ability to travel along nerve cells and reside in the sensory cells by the spinal cord. Once the vector is in place, it will manufacture its medication. It will block the sensory signals in the spinal cord that cause reflexive bladder contractions,” said Argyrios Stampas, MD, MS, lead investigator for the Houston site of the trial and associate professor with the Department of Physical Medicine and Rehabilitation in McGovern Medical School at UTHealth Houston. “This is the science fiction stuff that I dreamed about as an undergrad.”

Current treatment with BOTOX® for neurogenic bladder requires multiple injections, as many as 30, into the detrusor muscle of the bladder every six months. Preclinical study results showed that EG110A could last for several years.

“When people living with spinal cord injury are surveyed, bowel and bladder issues are their top priority,” said Stampas, director of Spinal Cord Injury Medicine Research at TIRR Memorial Hermann. “The opportunity to have one procedure that could relieve incontinence for years would be a huge improvement on their quality of life.”

The 52-week, Phase Ib/IIa clinical trial will enroll people from 18 to 75 years of age who are at least 12 months post-spinal cord injury. The trial includes a five-year safety follow-up period. Because it is a first-in-human study, an overnight hospital stay is required after the bladder injections. Visit-related expenses are reimbursed. The drug has received investigational new drug clearance from the U.S. Food and Drug Administration.

Houston is one of four sites across the country for the study. The others are Rancho Los Amigos National Rehabilitation Center in Los Angeles; University of Michigan Rogel Cancer Center in Ann Arbor, Michigan; and Sidney Kimmel Medical College in Philadelphia.

The one-of-a-kind patch, which uses donated cryopreserved umbilical cord to repair a baby’s spine in utero for spina bifida, was researched and tested by a multidisciplinary team led by Ramesha Papanna, MD, MPH, professor and director of the Division of Fetal Intervention in the Department of Obstetrics, Gynecology, and Reproductive Sciences at McGovern Medical School at UTHealth Houston.

“Fetal medicine and surgery are at an inflection point, shaped by rapid technological advancements,” said Papanna, who is the executive director of the new Fetal Institute. “This evolution calls for innovation to enhance outcomes not only for mother and baby, but also for their family and community. UTHealth Houston Fetal Institute is poised to lead the way, setting new standards in fetal diagnosis and therapy and advancing the field of fetal medicine.”

The university-wide institute, one of the first in the nation, will serve as a multidisciplinary center for research, education, and patient care for fetal intervention, maternal-fetal care, early genetic testing, maternal mental health, fetal diagnosis and therapies, and research discoveries.

“We are excited to see the launch of this new Fetal Institute that combines the strengths of our fetal medicine teams and expertise from several of our schools to create a destination service for life-changing interventions not possible anywhere else,” said Kevin Morano, PhD, senior vice president of Academic and Faculty Affairs at UTHealth Houston; Roger J. Bulger, MD, Distinguished Professor at McGovern Medical School; and board member of the new institute. 

Along with McGovern Medical School, the institute includes faculty at Cizik School of Nursing at UTHealth Houston, McWilliams School of Biomedical Informatics at UTHealth Houston, and UTHealth Houston School of Public Health. The institute is also collaborating with Children’s Mercy Research Institute in Kansas City, Missouri.

The Fetal Institute is also supported by the Department of Obstetrics, Gynecology, and Reproductive Sciences at McGovern Medical School. 

“We are proud to be part of Dr. Papanna’s vision for the future of fetal therapy,” said Sean Blackwell, MD, vice president of Strategy and Development for Obstetrics and Gynecology; professor and chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences; Memorial Hermann Chair; and Emma Sue Hightower Development Board Professor in Obstetrics, Gynecology and Reproductive Sciences. “Being on the cutting edge of research and innovative care is a key part of our mission; it’s why we are here at UTHealth Houston. I’m sincerely appreciative of the support by UTHealth Houston leadership to help make the institute possible.” 

The institute builds on the success of the UTHealth Houston Fetal Center, which was founded and is co-directed by KuoJen Tsao, MD, professor and chief of the Division of General and Thoracic Pediatric Surgery at McGovern Medical School, and Anthony Johnson, DO, professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences.

“We are incredibly fortunate to have the faith and trust of so many patients and their families over the years. Entrusting us to care for them during one of the most challenging times of their lives is a privilege. The Fetal Institute, led by Dr. Papanna, will continue to allow us to provide the most advanced care for our patients,” said Tsao, who is The Children’s Fund, Inc. Distinguished Professor in Pediatric Surgery at McGovern Medical School.

“In just over a decade, the Fetal Center has become recognized as an international referral center for the diagnosis and treatment of fetal disorders,” Johnson said. “With the establishment of the Fetal Institute, UTHealth Houston has demonstrated the university’s commitment to critical research and clinical care in the rapidly expanding field of fetal medicine.”  

Core leaders of the institute are Papanna; Jerrie Refuerzo, MD; Lovepreet Mann, MBBS; Jimmy Espinoza, MD, MS; Blair Stevens, MS; and Ashley E. Salazar, DNP, APRN, all with the Department of Obstetrics, Gynecology, and Reproductive Sciences. 

Morano is also a faculty member at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences.

Recently published in Heart, a BMJ Journal, the research revealed that rare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of early-onset bicuspid aortic valve participants. The research demonstrated that variations in chromosome 22 may contribute to the individual severity of nonsyndromic bicuspid aortic valve disease and the risk for complications.

Bicuspid aortic valve disease, where the aortic valve has two leaflets instead of the normal three, is the most common congenital heart defect, affecting up to 2% of the population. The condition is present from birth and is usually caused by the dominant inheritance — meaning it can be inherited from just one parent — of many gene mutations. The condition can lead to complications as severe as thoracic aortic aneurysms, weakening of the aortic wall, and aortic stenosis, or narrowing of the aortic valve. Nonsyndromic means that the condition is not part of another syndrome.

Research has shown that duplications or deletions of genomic DNA in regions that regulate cardiac development contribute to congenital defects. But less is known about variants in the 22q11.2 region and nonsyndromic bicuspid aortic valve. Sara Mansoorshahi and Catherina Tovar Pensa, third-year medical students at McGovern Medical School at UTHealth Houston, are working to close that gap.

“Our study focused on assessing the role of variants in the 22q11.2 region in patients with early onset bicuspid aortic valve, and to determine if these variants could potentially be considered as part of risk stratification for bicuspid aortic valve patients and help predict complications and guide further management,” said Tovar Pensa, co-first author.

DiGeorge syndrome, a 22q11.2 deletion syndrome, is caused when a small portion of chromosome 22 is missing. The condition can occur in individuals born from a parent with the dominant contiguous gene or parents without the gene. Variants in 22q11.2 deletion syndrome can cause complications beginning at birth due to congenital heart or vascular malformations, learning difficulties, psychiatric conditions, immunodeficiencies, and kidney or urinary tract anomalies. 

Researchers used whole genome microarray genotyping on 272 bicuspid aortic valve patients with early onset valve or aortic disease and 272 biological relatives. They analyzed all copy number variations in the 22q11.2 chromosome while participants completed a questionnaire about their cardiovascular, endocrine, urogenital, musculoskeletal, developmental, and psychiatric histories. Copy number variation refers to a circumstance where the number of copies of a specific segment of DNA varies in the genomes of different people.

Several variants identified in the research involved the genes TBX1, CRKL, HIC2, and  MAPK1, which are required for vascular development, especially the left ventricular outflow tract, which passes blood through the aorta. Until now, a variation in TBX1 had not been explicitly associated with bicuspid aortic valve disease. Mutations in TBX1 and other 22q11.2 genes may cause learning differences, intellectual disabilities, psychiatric disease, seizures, muscular hypotonia, or stunted growth. These features may alert physicians to the need for genetic testing for 22q11.2 copy number variants in bicuspid aortic valve patients who present with early onset complications or have additional congenital heart malformations.

“It was reassuring to see it was not a small increase, but a statistically significant increase in these genetic variants among bicuspid aortic valve population, and to be able to show that with more research in this area, this region could be an important area of interest for future genetic testing,” said Mansoorshahi, a co-first author.

The research was funded in part by the National Institutes of Health (R01HL137028, R21HL150383, R01HL114823,  and R21HL150373).

Additional authors from UTHealth Houston included co-first author Siddharth K. Prakash, MD, PhD; Courtney McNeely, MD; and Dianna Milewicz, MD, PhD; as well as former fellows, Abi Watts, MD, now with Texas Tech University Health Science Center, and Helene DiGregorio, MD, now with Houston Methodist Hospital. Additional co-authors included Dawn S. Hui, MD, The University of Texas Health Science Center at San Antonio; Anna Sabaté-Rotés, MD, PhD, Vall d’Hebron University Hospital in Spain; Anji T. Yetman, MD, University of Nebraska Medical Center; Hector I. Michelena, MD, Mayo Clinic; Malenka M. Bissell, MD, DPhil, University of Leeds in the United Kingdom; Maria Grazia Andreassi, PhD, MSc, and Ilenia Foffa, PhD, Istituto di Fisiologia Clinica in Italy; Anthony Caffarelli, MD, Hoag Memorial Hospital Presbyterian in Newport Beach, California; Yuli Y. Kim, MD, University of Pennsylvania; Rodolfo Citro, MD, PhD, University of Molise Responsible Research Hospital in Italy; Margot De Marco, PhD, University of Salerno in Italy; Justin T. Tretter, MD, Cleveland Clinic; Kim L. McBride, MD, University of Calgary; Simon C. Body, MBChB, MPH, Boston University School of Medicine; Julie De Backer, MD, PhD, Ghent University in Belgium; and Laura Muiño Mosquera, MD, PhD, Ghent University Hospital in Belgium.

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Neurologic conditions including stroke, Parkinson’s disease, and vascular cognitive impairment and dementia contribute to the leading causes of death and disability in the U.S. The goal of the project is to build an infrastructure for community-engaged research interventions for those three neurologic conditions affecting brain health.

“Historically, clinical trials for neurological conditions haven’t consistently or holistically included the voice of underserved communities that shoulder the largest burden of disease,” said Anjail Z. Sharrief, MD, MPH, principal investigator for the trial and professor with the Department of Neurology in McGovern Medical School at UTHealth Houston. “If community input is part of the research plan from the beginning, the clinical trial will more likely include a broader patient population, and research findings and outcomes will be more applicable to the wider range of patients affected by the conditions.”

For example, Sharrief said, designing clinical trials that require patients to come into the clinic during the work week instead of Saturdays limits the ability of lower-wage earners who would lose income by participating. Follow-up televisits instead of in-person visits also make a clinical trial easier for people to join. Including funding for transportation and bilingual research staff would also make it more possible for people from underserved communities to participate.

“We often develop trials for what we, the researchers, are able to do, not what the community is able to do,” Sharrief said.

The project will establish a Brain Health Equity Collaborative to facilitate the academic and community partnerships for clinical trial development. The collaborative will include a community advisory board to review consent forms, assessment questions, and other components of a research trial to ensure they are relatable to a wide range of patients. A community oversight committee will ensure that patient and caregiver voices are being heard and that trials are adhering to protocols for community engagement.

“When you cannot recruit patients from certain communities to participate in a clinical trial, it’s not merely an issue of trust or interest — you’ve made it too hard for them to participate,” Sharrief said. “This is super exciting because it marries our passion for research with our commitment to community engagement and empowerment.”

Community partners include ProSalud, Gulfton Home Community, African American Male Wellness Agency, and the Christopher Pichon II Foundation.

Co-investigators for the trial from the Department of Neurology at McGovern Medical School are Elizabeth Noser, MD, associate professor and James C. Grotta, MD Chair in Neurological Recovery and Stroke; Chigozirim Izeogu, MD, MPH, assistant professor; Mya Schiess, MD, professor, director of Movement Disorders and Neurodegenerative Diseases, and Adriana Blood Distinguished Chair in Neurology; Shivika Chandra, MD, associate professor and chief of neurology at Harris Health Lyndon B. Johnson Hospital; and Kendra Anderson, PhD, assistant professor.

Other co-investigators are Jose-Miguel Yamal, PhD, associate professor of biostatistics at UTHealth Houston School of Public Health; Amy Franklin, PhD, associate professor and associate dean for Student, Faculty, and Community Affairs at McWilliams School of Biomedical Informatics at UTHealth Houston; and Logan Thornton, DrPH, MPH, director of Population Health and Evidence-Based Practice Healthcare Transformation Initiatives at UT Physicians. 

Yamal is a member of The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences. Sharrief, Yamal, Noser, and Anderson are members of the UTHealth Houston Institute for Stroke and Cerebrovascular Diseases.

Funding came from the National Institute of Neurological Disorders and Stroke (1R01NS40001-01), part of the NIH.

The study was recently published in Nature Communications.

Led by Dennis Lal, PhD, director of the Center for Neurogenetics and associate professor of neurology at McGovern Medical School at UTHealth Houston, the research team analyzed data from 1,386 human brain tissues for somatic variants in the genes of individuals undergoing epilepsy surgery. Somatic variants are DNA changes that occur after conception and can only be identified in the brain tissue.

According to the Centers for Disease Control and Prevention (CDC), epilepsy affects approximately 3.4 million people in the United States, and 1 in 3 patients struggle with drug-resistant forms of the condition. By linking epilepsy to specific genetic mutations, the research offers a new framework for understanding the disorder and developing therapies that address its root causes.

The most extensive study of its kind, the research identified two novel genes, DYRK1A and EGFR, and their genetic mutations linked to epileptic brain lesions.

“Discovering these genes not only helps us better understand the biology behind epilepsy but also reveals specific traits in tissues, making them valuable tools for diagnosing the condition,” Lal said.

Through the research, Lal and his team confirmed four well-established gene-disease associations and provided evidence for eight more. Once brain tissue testing after surgery becomes clinically available outside of research, these findings could offer long-awaited answers about what causes the condition of these patients with a drug-resistant form of the disease, he said.

The project also revealed that many genes identified with associated variants interact with biological pathways targeted by FDA-approved cancer drugs. While epileptic lesions share genetic similarities with tumors, they differ in several key ways. Neurons — the affected cells in epilepsy — do not replicate like cancer cells, opening opportunities to repurpose existing cancer drugs for epilepsy treatment.

“For those with epilepsy, their caregivers, and health care providers, our research represents a step closer to understanding epilepsy at its most fundamental level while improving patients’ quality of life,” Lal said.

Co-authors included Christian Bosselman, MD, of Universitätsklinikum Tübingen; Costin Leu, PhD, and Tobias Brünger, PhD, of UTHealth Houston; Lucas Hoffman, MD, PhD, of the University of Washington; Katja Kobow PhD, of Universitätsklinikum Erlangen; Imad Najm MD, of the Cleveland Clinic; and Ingmar Blumcke, MD, of Universitätsklinikum Erlangen – Institute of Neuropathology.

Funded by a $3.5 million grant from the National Institutes of Health, researchers from the Department of Orthopedic Surgery at McGovern Medical School at UTHealth Houston, in collaboration with the Steadman Philippon Research Institute in Vail, Colorado, are working to establish a standardized approach for ACJ reconstruction. The joint is particularly vulnerable in young athletes engaged in contact sports such as football and hockey.

“Currently, there is no standardized approach to treating ACJ injuries, which makes it challenging to determine the best method to repair an ACJ injury and position patients for successful, long-term outcomes,” said Payam Zandiyeh, PhD, assistant professor in the Department of Orthopedic Surgery and the lead investigator on the project. “If left untreated, these injuries can lead to chronic pain, decreased mobility, and other complications, underscoring the need for an established treatment protocol.”

The study, titled “Multicenter, Longitudinal Study of Acromioclavicular Joint Reconstruction Techniques for Restoring Shoulder Complex Biomechanics and Soft Tissue Health,” is the first of its kind to compare multiple surgical methods for ACJ reconstruction. Specifically, the study will evaluate three ACJ reconstruction techniques:

•                 Coracoclavicular (CC) ligament reconstruction alone, which stabilizes the joint vertically but does not address horizontal instability, potentially leaving the joint biomechanically vulnerable.
•                 Combined ACJ and CC reconstruction with bone tunnels, which enhances both vertical and horizontal stability by reconstructing the AC and CC ligaments using grafts or sutures passed through drilled bone tunnels in the clavicle and coracoid. While anatomically accurate, this method carries risks of fractures due to stress on the bone tunnels, requiring careful surgical technique and postoperative care.
•                 Combined ACJ and CC reconstruction without bone tunnels, which is a newer, tunnel-free technique designed to reduce fracture risks while maintaining joint stability. However, its long-term effectiveness in preserving joint function is not yet fully understood.

The study aims to identify the most effective technique for restoring stability, minimizing complications, and improving long-term outcomes, particularly for young athletes prone to ACJ injuries.

The study is built on the collaborative expertise of a multidisciplinary team. James Gregory, MD, associate professor in the Department of Orthopedic Surgery and a leading orthopedic surgeon on the project, played a pivotal role in shaping the study’s surgical protocols and ensuring their practical application for patient care.

“Dr. Gregory’s extensive surgical expertise is at the heart of this research,” Zandiyeh said. “His insight into the complexities of ACJ injuries and reconstruction techniques ensures that our work is both clinically relevant and impactful for the patients we aim to serve.”

The study also includes Manickam Nicks Kumaravel, MD, professor and Memorial Hermann Chair in the Department of Diagnostic and Interventional Imaging at McGovern Medical School, who will provide imaging diagnostics expertise for the study. Michael Jacobs, PhD, professor and Chair in Biomedical Engineering in the Department of Diagnostic and Interventional Imaging, contributed to the study’s state-of-the-art magnetic resonance imaging (MRI) sequence design and analysis. Dejian Lai, PhD, professor of biostatistics and data science at UTHealth Houston School of Public Health, contributed to the study’s advanced biostatistical and data science analyses.

The study uses state-of-the-art imaging technologies, including dynamic stereo X-ray, which provides real-time 3D imaging of joint movement, and MRI, offering detailed analysis of soft tissue health and shoulder function. Recovery progress will be monitored at six- and 12-months post-surgery.

In addition to imaging, researchers will incorporate patient-reported outcomes and surveys to evaluate the impact of surgical techniques on mobility, stability, and overall recovery from the patients’ perspective.

“This multifaceted approach allows us to gain a comprehensive understanding of how different procedures influence recovery,” Zandiyeh said. “By combining advanced imaging with patient feedback, we can identify the techniques that offer the best outcomes for long-term shoulder health.”

The study’s findings are expected to guide the development of evidence-based treatment protocols, helping physicians select the most effective surgical methods tailored to each patient’s needs.

“This research has the potential to establish a gold-star standard of treatment for ACJ injuries,” Zandiyeh said. “By providing physicians with evidence-based surgical options, we hope to help young athletes return to sports with a positive prognosis for long-term shoulder health.”

Since being diagnosed with epilepsy at 8 years old, Luke was used to having seizures, but his condition began to worsen, and he started experiencing grand mal seizures when he was 18 years old. They were so bad that, at one point, he was getting them every two weeks.

“I basically lost my career,” he said. “I had to get an ambulance ride from class and had to stop going to the fire academy. I started having grand mal seizures more frequently and more often, then I would go stretches with no seizures, and then they would just come back.”

Luke began to seek help, but each time he was met with the same option — brain surgery — something Luke knew he didn’t want. Luke and his wife decided to get a second opinion and  found Nitin Tandon, MD, professor of neurosurgery with McGovern Medical School at UTHealth Houston and vice president of strategy and development at UTHealth Houston Neurosciences.

“I wanted the best of the best,” Luke said. “I had been praying there was another option other than surgery. We were not fans of removing part of my brain or laser ablation. A friend was able to help us research and gave us a list of the top 10 physicians I could see, and I really liked Dr. Tandon. His background was so specific to what I had. I was drawn to him, it just felt right. I had been praying and I asked God to tell me that if this was our doctor, let there be another option.”

After meeting with Tandon, Luke was given a different choice — stem cell therapy.

Tandon had just been approved to enroll patients into a national Phase I/II clinical trial study that is testing whether a neural cell therapy product can help inhibit the abnormal electrical activity that leads to an epileptic seizure.

“When the stem cells were presented to us, it was mind blowing. It felt like I got my answer,” Luke said. “I have been in hospitals my entire life; I have sort of built up what they call ‘white coat syndrome,’ but with Dr. Tandon, it was gone. He was incredible; he and his entire staff made me feel great.”  

In August, Luke became the first patient to enroll in the clinical trial. Since the minimally invasive surgery to place the stem cells, he has experienced just one seizure.

“Praise be to God and to my amazing wife, who helped me find Dr. Tandon. Right now I feel great, and I have only had one grand mal seizure since the surgery, so things are progressing already,” Luke said.  

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A device that delivers direct stimulation to the brain was found to be a safe and effective means of treating depression at home, according to a new study by researchers at UTHealth Houston; the Institute of Psychiatry, Psychology & Neuroscience at King’s College London; and the University of East London.

The research was published in Nature Medicine on Oct. 21, 2024.

Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that applies a weak, direct current of between 0.5 to 2 milliampere to the scalp via two electrodes. It is already commonly used in clinics to treat conditions such as psychosis and eating disorders. The clinical trial assessed tDCS that was used in a home setting and self-administered by patients.

King’s College London led the international study. Co-author and lead investigator for the U.S. site was Rodrigo Machado-Vieira, MD, PhD, MSc, professor with the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences in McGovern Medical School at UTHealth Houston.

“The results from this study, which tested home-based tDCS, may represent an important advance in the mood disorders field for improving feasibility and therapeutic response with this new neuromodulation modality,” Machado-Vieira said. “These latest results confirmed a positive profile for safety and efficacy similar to early studies with patients with depression and bipolar disorder, and the home-based therapy may facilitate access of this treatment to a larger number of patients.”

Researchers found that participants in the active arm of the trial showed significant improvements in the severity of their depression, as well as an overall clinical response and remission, compared to those in the inactive placebo control arm. The rates of treatment response and remission were three times higher in the active treatment arm compared to the placebo arm, with 44.9% in the active arm demonstrating a remission rate compared to 21.8% of the control group.  

“The burden of depression is mostly keenly felt by the 280 million people worldwide currently managing symptoms. While a combination of antidepressants and therapy generally proves to be effective for many people, medication can have side-effects that some can find disruptive. Our study has demonstrated that tDCS is a potential first-line option that could help those in need,” said Cynthia Fu, MD, PhD, the study’s senior author and a professor of affective neuroscience and psychotherapy at King’s College London.

“There is no such thing as the perfect medical intervention. Medication can have unintended side effects, while therapy is both time- and resource-intensive. Our hope is that tDCS can provide a viable third alternative for people with moderate to severe depression to help them better manage their symptoms,” said Rachel Woodham, MSc, the study’s first author and a research assistant at the University of East London. 

“This breakthrough publication crowns the eight years of work that has been done by the fantastic team at Flow and the team of researchers at King’s College London, UTHealth Houston, and the University of East London, who led the study. Nature Medicine is one of the top medical journals in the world, and this publication speaks to the quality of the study design and results. Our core mission was, and still is, to create a treatment that is effective, safe, and accessible to as many people as possible,” said Daniel Månsson, chief clinical officer and co-founder of Flow Neuroscience, which funded the study.

UTHealth Houston co-author and co-lead investigator for the U.S. site was Jair Soares, MD, PhD, professor and the Pat R. Rutherford, Jr. Chair in Psychiatry in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School.

“The study results bring promise that an innovative treatment modality may become available for patients suffering from mood disorders some time in the near future,” Soares said.

“For me, it was a godsend,” she said.

Ashley had always struggled a little with depression, but in recent years, she sometimes had difficulty getting out of bed and finding joy in things, like publishing her photography book.

“It was as if my energy levels were depleted,” she said. “You view things from the outside and are unable to experience the positive emotions that come from things you’d normally enjoy.”

She was diagnosed with bipolar depression, but medications did not help. She saw an advertisement for a stem cell clinical trial for treatment-resistant bipolar depression at UTHealth Houston and signed up.

Bipolar disorder is characterized by shifts in mood, energy, and activity levels that can affect a person’s ability to carry out daily tasks, according to the National Institute of Mental Health. According to research published in 2023, 8 million Americans have bipolar disorder.

Ashley joined a double-blind, randomized, placebo-controlled trial that uses allogeneic mesenchymal stem cells, which are multipotent stem cells taken from an adult bone marrow donor. The mesenchymal stem cells are manufactured in the Judith R. Hoffberger Cellular Therapeutics Laboratory at UTHealth Houston, a state-of-the-art Food and Drug Administration-registered facility designed to comply with current good manufacturing practice. 

“Since mesenchymal stem cells are known to counteract inflammation and promote neurogenesis, we are hopeful that they provide an innovative therapy for patients with treatment-resistant bipolar depression,” said Jair Soares, MD, PhD, vice president of Behavioral Sciences at UTHealth Houston and professor and chair in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Health Sciences at McGovern Medical School at UTHealth Houston. “We think the stem cells might lessen some of the inflammation in the brain that can lead to mood fluctuations.”

In previously published studies by researchers at UTHealth Houston, stem cells have shown a dampening effect on inflammation, which has been linked to bipolar disease. Inflammatory markers have also been associated with a decreased likelihood of response to treatment in people with bipolar disease. 

“We have a very strong stem cell program at UTHealth Houston, and we paired up with stem cell researchers in pediatric neurosurgery and neurology who have been testing stem cells for other brain disorders,” said Soares, who is also the Pat R. Rutherford, Jr. Chair in Psychiatry, executive director of the John S. Dunn Behavioral Sciences Center at UTHealth Houston, and dean of the UTHealth Houston School of Behavioral Health Sciences. “This is an exciting time to be at the forefront of a field where we are able to test this new technology and see if it may offer some help for patients with bipolar disorder.”

Because the clinical trial is randomized and double-blind, Ashley doesn’t know whether she received the stem cells or a placebo. But she said she feels better since joining the study.

“My energy levels are much better. I’m able to keep my routine, and I started working out again,” she said. “I am participating in life. I feel balanced.”

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The five-year study, funded by an award (1R01NS138765-01) from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, will include the creation of a machine-learning tool that can be used to predict which stroke patients with large blood vessel blockages will benefit most from endovascular therapy.

“There have been two tenets for treating large vessel occlusions that we have followed,” said Sunil A. Sheth, MD, principal investigator and associate professor in the Department of Neurology at McGovern Medical School at UTHealth Houston. “The first is that the sooner you treat them, the better, and the second is that if a large area of the brain is already dead based on imaging, there’s no point in trying to open up the blockage.”

But Sheth said in the past few years, stroke physicians have noted that those tenets don’t always hold true. New studies are showing that even a day or more after a stroke, and even with a large area of damage, patients can still have good clinical outcomes with endovascular therapy. Alternately, patients who meet the metrics predicting a good outcome after endovascular therapy sometimes don’t benefit. While doctors can unblock the artery and restore blood flow in over 90% of patients, over 50% of those are still left with moderate to severe disability.

“This is shaking our core of deciding who we treat, and when, and how, but also, how we are evaluating them? Our current methods of determining benefit with imaging are not good enough,” Sheth said.

According to the CDC, an ischemic stroke occurs when a blood clot or other particle blocks a blood vessel in the brain. In about one-third of patients, clot-busting medications can break up the occlusion. But when the blockage is large, medication alone often doesn’t work. So physicians may opt to remove it with endovascular therapy, where a catheter is guided through an artery in the groin or wrist and up into the brain to remove the clot.

Sheth is joined by two other lead investigators: Luca Giancardo, PhD, associate professor with the Department of Health Data Science and Artificial Intelligence at D. Bradley McWilliams School of Bioinformatics at UTHealth Houston, and Santiago Ortega-Gutiérrez, MD, MSc, clinical associate professor of neurology in Carver College of Medicine at University of Iowa Health Care.

They will create a database of imaging and clinical outcomes in patients whose blockages have been successfully opened, called reperfusion, from three U.S. hospitals. This will allow them to identify clinical and imaging-based predictors of damage in the brain after reperfusion.

The UTHealth Houston researchers will create a machine-learning model to predict the likelihood of brain tissue viability and clinical outcomes from data taken before the endovascular therapy treatment and after reperfusion. A deep-learning model will also be created with imaging information, along with clinical history and stroke-severity measures, to help identify those patients where recanalization with endovascular therapy treatment alone is not enough to result in good clinical outcomes.

“We are letting an algorithm learn the visual features that are predictive to doing well, or not doing well,” Giancardo said. “It’s not that machine learning or AI see things that are invisible. They see things that are there. But finding correlations between multiple modalities, with longitudinal data, it’s hard because they can be very subtle.”

The deep-learning model will also learn from the change between pre- and post-therapy with imaging and clinical variables to predict clinical outcomes in patients treated with clot-busting medications and/or endovascular therapy treatment.

“The model is hopefully going to see things that we don’t see, that we don’t think to see, that we wouldn’t even think to analyze in certain ways,” Sheth said. “So, this model will hopefully be able to outperform what we can do with our eyes.”

Co-investigators for the trial are Eunyoung Angela Lee, PhD, assistant professor in the Department of Neurology at McGovern Medical School, and Maxim Mokin, MD, PhD, professor of neurosurgery in the Department of Neurosurgery and Brain Repair at the University of South Florida.

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