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Neurology & Neurosurgery

Children’s and UAB expanding access to promising DMD therapy

A researcher working in a lab at UAB (File photo)

By Angel Pine

Children’s of Alabama and the University of Alabama at Birmingham (UAB) Department of Pediatrics are expanding access to a promising investigational therapy for patients with Duchenne muscular dystrophy (DMD), offering new hope for families affected by the progressive neuromuscular disease.

Through an expanded access program, they will begin offering delpacibart zotadirsen, a novel antibody-oligonucleotide conjugate (AOC) developed by Avidity Biosciences. The program gives select patients access to the therapy before full U.S. Food and Drug Administration approval while researchers continue evaluating long-term outcomes.

Samantha Weaver, DNP, CRNP, assistant professor in the UAB Division of Pediatric Neurology, says the therapy represents an important step forward in the treatment of DMD.

Samantha Weaver, CRNP

“There is still no cure for Duchenne muscular dystrophy, therefore we are always interested in expanding access to therapies that may improve quality of life and slow disease progression,” she said.

Duchenne muscular dystrophy is an inherited neuromuscular disorder caused by changes in the DMD gene, one of the largest genes in the human body. The condition primarily affects boys because it is inherited in an X-linked pattern. Sequence changes in the DMD gene prevent the body from producing dystrophin, a critical protein that helps protect muscle cells during movement and contraction. Without dystrophin, muscles become increasingly damaged over time. “In the absence of dystrophin, fragile muscle fibers become susceptible to contractile injury, leading to damage and progressive weakness,” Weaver explained.

Early signs of DMD can include delays in walking, enlarged calf muscles, and weakness in the hips and thighs. Symptoms typically worsen throughout childhood, with many patients losing the ability to walk between ages 8 and 12 years of age. In later stages, the disease can affect the heart and lungs, leading to serious complications such as heart and respiratory failure.

UAB and Children’s currently care for approximately 80 patients with Duchenne muscular dystrophy through the multidisciplinary Muscular Dystrophy Association (MDA) clinic, the only nationally designated MDA care center in the state.

Over the past two decades, advances in genetic research have significantly improved treatment options for DMD. While early therapies focused primarily on reducing inflammation through long-term steroid use, newer approaches aim to address the root cause of the disease via dystrophin restoration.

Steroids remain a standard treatment to help slow the inflammatory damage that occurs alongside muscle breakdown. Combined with multidisciplinary care, these therapies have improved life expectancy for many patients. “Thanks to routine corticosteroid treatment and coordinated multidisciplinary care, life expectancy for individuals with Duchenne muscular dystrophy has improved dramatically, with many patients now surviving into adulthood,” Weaver noted.  

Delpacibart zotadirsen is an antibody-oligonucleotide conjugate, or AOC. An AOC uses a laboratory-made genetic molecule or PMO to bind to dystrophin RNA. The PMO helps the cell bypass the faulty sections of genetic instructions. A new “genetic blueprint” is formed, one that provides instructions for restored dystrophin production. Rather than permanently changing DNA, AOC therapy works by modifying RNA instructions after they are copied from the gene but before they are used to build proteins. “Although full dystrophin restoration may not be possible, enough functional protein may create a milder disease phenotype,” Weaver explained. “Even partial dystrophin restoration can lead to meaningful improvements in disease severity and progression.”

Earlier generations of exon-skipping therapies have provided modest results. Passive uptake of molecules into muscle cells produced small increases in dystrophin on muscle biopsy and limited improvements in motor function. While those therapies received accelerated FDA approval, researchers continued working to improve the selectivity of these treatments.

Delpacibart uses an antibody-mediated delivery system designed to improve uptake into muscle cells. By selectively binding to muscle cells, researchers can better tailor dosing and reduce the risk of toxicity.

According to Weaver, this next-generation approach may significantly improve dystrophin production compared to previous therapies.

In randomized, placebo-controlled trials, data supported a mean increase of approximately 25% of normal dystrophin production from baseline after four months of treatment, with some patients reaching as high as 54% restoration. Researchers also observed more than an 80% reduction in creatine kinase, a muscle enzyme that is typically elevated in patients with DMD due to ongoing muscle damage.  

“We do not currently have therapies that produce this degree of creatine kinase improvement,” Weaver said. “Although these findings are encouraging in small research numbers, how these will translate to actual strength and slowing of disease is still being studied.”

The therapy is delivered once every six weeks because it does not permanently alter DNA and must be re-dosed to maintain its effect.

Only a small percentage of patients with Duchenne muscular dystrophy are eligible for exon 44 skipping therapy. Weaver estimates about 6-7% of patients have gene variants that make them candidates for this treatment. While that percentage is relatively small, Weaver emphasizes the broader significance of the program. “Six percent may not sound like a lot, but it is still meaningful for the patients who qualify,” she said. “More importantly, if this approach continues to succeed, the hope is that the same technology can be adapted to target other variants and help many more patients in the future.”

The expanded access program has received institutional approval and is supported through all required regulatory channels. UAB is now preparing to enroll eligible patients.

For families affected by Duchenne muscular dystrophy, each scientific advancement represents another step toward better treatment options and improved outcomes. “This is a really exciting development in Duchenne care,” Weaver said. “Every breakthrough moves us closer to changing the long-term trajectory of this disease.”

August 6, 2026 by
Neurology & Neurosurgery

Time is brain: A pediatric code stroke program

Code Stroke at UAB and Children’s of Alabama is designed to improve recognition, response and outcomes. (Stock photo)

By Heather Watts

A stroke is often thought of as a condition of adulthood, yet it remains a significant and underrecognized cause of morbidity and mortality in the pediatric population. Despite being cited among the leading causes of death in children, pediatric stroke is frequently missed or diagnosed late, in part due to its relative rarity, diverse clinical presentations and the unique risk factors that distinguish it from adult stroke. As a result, many children with stroke present outside the narrow window during which acute interventions may be considered, limiting opportunities for therapies that can meaningfully alter neurologic outcomes. In pediatric stroke, as in adult stroke, the principle remains the same: Time is brain.

Improving pediatric stroke education

During her training in child neurology at the University of Alabama at Birmingham (UAB), Sarah Novara, M.D., MSQHS, FCNS, associate professor in the Division of Pediatric Neurology, had several patient encounters that highlighted both the devastating potential of delayed stroke recognition in children and the extraordinary opportunity that exists when stroke is identified and treated promptly.

“When we were able to quickly evaluate and treat stroke symptoms in our pediatric patients, we saw amazing neurologic recovery,” Novara explained. “Seeing the importance of early stroke recognition firsthand inspired me to improve our pediatric stroke education and standardization processes at Children’s of Alabama and UAB.”

As a senior resident, Novara developed pediatric stroke education and streamlined order sets and processes for residents, fellows and faculty. Novara worked with Tony McGrath, M.D., associate professor in the Division of Pediatric Neurology and Nancy Tofil, M.D., M.Ed., professor in the Division of Pediatric Critical Care, to develop a pediatric stroke simulation as part of pediatric stroke education for trainees and faculty. “The simulation has been highly efficacious in advancing pediatric stroke evaluation and management knowledge in a variety of learner settings since its creation,” Novara explained.

From education to systems change: Creating a Pediatric Code Stroke

Once on faculty at UAB, Novara continued her work with pediatric stroke education and began working on improving early stroke recognition among providers at Children’s and UAB by establishing a Code Stroke for pediatrics.

“We decided to model a Code Stroke process after our adult neurology colleagues and other select children’s hospitals across the U.S.,” Novara said. The pediatric Code Stroke initiative aims to offer necessary, efficient evaluation and management of patients presenting with signs of possible stroke, and if inevitably they have not had a stroke, the Code Stroke process assists in evaluating and managing conditions that mimic stroke and deserve appropriate treatment. 

In the summer of 2024, the Code Stroke working group met to create the Children’s of Alabama Code Stroke protocol for patients greater than one month of age with acute neurologic deficits and who were last known at their neurologic baseline less than 24 hours prior to presentation at the hospital. This is the window in which options of acute stroke intervention may be offered, if there are no contraindications. In addition to the protocol, order sets within EPIC were streamlined for the evaluation of Code Stroke patients in the emergency department (ED) or on the hospital floors, and stroke patient admission order sets were provided as well.

This Code Stroke effort was spearheaded by Novara, Tofil and Jeffrey Blount, M.D., MPH, professor in the Division of Pediatric Neurosurgery. It also included colleagues from pediatric emergency medicine, neuro-interventionalists, radiology, nursing, and operators.

After the Code Stroke protocol was established and education was provided across the pediatric divisions, the Children’s of Alabama Code Stroke went live in September 2024. As of July 2026, a Code Stroke had been called 131 times (either in the ED or on a hospital floor). Approximately 12% of these Code Strokes have identified ischemic or hemorrhagic strokes, allowing for efficient evaluation and management. Several of the pediatric acute ischemic stroke patients have even benefited from an acute thrombectomy performed by the on-call neuro-interventionalists. Code Stroke patients with hemorrhagic stroke have benefited from the expedited care of the pediatric neurosurgery team. Many of the Code Stroke patients have made remarkable recoveries.

“We have been very excited about the success of multidisciplinary care within the Code Stroke process, as many patients—even those without strokes—have received expedited treatment for life-altering conditions,” Novara said.

“The Code Stroke working group meets quarterly to continuously discuss ways in which to improve our Code Stroke protocol and to collaborate together as we try to provide the best care for our patients,” Tofil added.

Expanding care beyond the acute phase: Pediatric Stroke Clinic

In early 2025, a monthly Stroke Clinic was established by Novara and McGrath to provide a unique pediatric stroke follow-up clinic that offers ongoing patient support, education and follow-up care, including best efforts at secondary stroke prevention. 

In the monthly stroke clinic, the pediatric neurology team collaborates with pediatric hematology and neurosurgery colleagues in the care of unique pediatric patient populations seen in their clinics who are at risk for stroke. The stroke clinic also allows the pediatric neurology team to provide effective transition of care for patients from pediatric to adult stroke care at UAB as needed.  

The pediatric stroke clinic at Children’s of Alabama is a participating site within the International Pediatric Stroke Study, which is a research group working hard within the International Pediatric Stroke Organization to expand the knowledge about pediatric stroke and best practices for these unique patients.

The Code Stroke program has demonstrated that targeted educational initiatives, combined with the development of standardized, multidisciplinary response protocols, can meaningfully improve the evaluation and management of children presenting with possible pediatric strokes.

As awareness grows and standardized care pathways expand, there is an opportunity to reduce the burden of pediatric stroke and ensure that children receive timely, evidence-informed care when minutes matter most.

July 22, 2026 by
Neurology & Neurosurgery

Lalor appointed Director of Pediatric Neurology

Kathryn Lalor, M.D. was appointed director of the Division of Pediatric Neurology in May 2026.

By Angel Pine

As the new director of the Division of Pediatric Neurology, Kathryn Lalor, M.D., aims to build on the strong foundation already established within the division.

Lalor, who was appointed to the position in May, has been a valued member of the division as associate professor, contributing to its continued growth in both clinical care and academic excellence. In her new role, she will lead efforts to further strengthen the division’s mission across patient care, education, and research.

“Dr. Lalor joined the division in the midst of its recent growth,” said Leon Dure, M.D., professor and former division director of Pediatric Neurology. “She has the skills and temperament needed to ensure UAB Pediatric Neurology’s reputation of academic and clinical excellence.”

“This appointment represents an opportunity to grow into a new kind of leadership which I plan to approach with humility and intentionality,” Lalor said. “Leon Dure has left big shoes to fill, but I am thankful to continue growing the supportive culture he has fostered.”

Lalor also expressed enthusiasm about the division’s future, noting its significant growth over the past decade and the opportunity to build on that momentum. Lalor emphasized the importance of collaboration across the division, adding, “If you want to go fast, go alone. If you want to go far, go together,” as she looks forward to working alongside faculty, staff and trainees to continue advancing care for children across Alabama.

Her appointment reflects the department’s continued commitment to strong leadership and advancing pediatric neurological care.

July 22, 2026 by
Neurology & Neurosurgery

McRae Addressing PTSD in Kids With Hydrocephalus

Elizabeth McRae, Ph.D., is a psychologist embedded within the Children’s of Alabama Neurosurgery team.

The young child was beyond terrified of the hospital. Born with hydrocephalus, he’d had numerous surgeries, and his anxiety was so high that just getting him to the car for doctors’ appointments was a struggle. It could take an hour to get from the parking garage to the hospital entrance given his tantrums and refusal to walk. The behavior continued at home every time someone opened the front door. “The parents really couldn’t live their life because it was so intense,” said Elizabeth McRae, Ph.D., a pediatric clinical child psychologist at Children’s of Alabama.

Here was a clear case of post-traumatic stress disorder (PTSD) related to the boy’s illness. Resolving it is exactly what McRae, who joined the neurosurgery team in January 2024, was hired to do.

For years, neurosurgeons and families caring for children with hydrocephalus understood the physical stakes: shunts that could fail without warning, repeated surgeries, emergency trips to the hospital. What was less visible—and often unaddressed—was the psychological toll of living in constant vigilance both for the patient and the family.

Earlier work at Children’s helped bring that reality into focus, documenting high rates of medical post-traumatic stress among families coping with hydrocephalus. But identifying the problem was only the beginning.

“Based on the results of that previous survey, we brought Dr. McRae on board and embedded her in our neurosurgery practice to provide psychological support for PTSD from screening and diagnosis through interventions to getting people plugged in to community resources,” pediatric neurosurgeon Brandon Rocque, M.D., said.

What’s emerged is an integrated, trauma-informed model of care that treats psychological health as part of standard neurosurgical practice.

From Measuring Stress to Building Resilience

Families of children with hydrocephalus face a unique kind of uncertainty, McRae said. Even when a child is medically stable, the possibility of sudden deterioration and a need for a new shunt never disappears. That’s why resilience, which she defines as strengthening the ability of families and patients to view difficulties as challenges rather than barriers, is so important.

Whether she’s meeting a family for the first time at diagnosis or after a child’s 10th surgery, she starts from the same place: helping them identify strengths they already have that can enable them to cope.

McRae also emphasizes connection. “One of the key predictors of potential traumatic stress is feeling like we’ve lost power and feeling isolated,” she said. “So if, right off the bat, we can empower them and encourage a connection, to me, those are two of the best things we can do up front.”

“There’s also a big piece of how do we prevent the trauma?” she continued. One approach, she said, is “taking a trauma-informed approach to our service so we mitigate the risk on the front end.” That includes explaining what’s going to happen to children; giving them options and a sense of control whenever possible; creating a sense of structure and predictability in the hospital setting as much as possible; and relying on other services such as Child Life to help children cope and adjust through play. 

McRae works closely with the surgeons, nurses and residents in both clinic and hospital settings, participating in the morning clinical discussions. Nurses refer families they see struggling, and surgeons seek her input about how to provide trauma-informed care in communication and interactions with patients.

The clinical model emphasizes brief, targeted interventions—an intentional choice in a population already burdened by multiple appointments. “I’m doing them a disservice if I can’t do something fairly efficiently,” McRae said.

These strategies were helpful with the aforementioned young child. McRae worked with him and his mother using developmentally appropriate coping strategies such as play-based breathing exercises, predictable reassurance and gradual exposure. She had him pretend to be a snake and breathe in slowly and deeply like a snake to quell his anxiety. A scavenger hunt throughout the hospital helped provide distraction so he could become comfortable in the medical setting. And Rocque met with him dressed in his blue scrubs for a meet-and-greet, no medicine involved, since the child was usually so frightened by anyone in blue scrubs. McRae also involved the boy’s mother in the interventions, providing a greater sense of control over the situation.

The result? The walk from the car to the hospital takes just a few minutes. The tantrums in the clinic are over. His parents have space to breathe. All this was achieved over the course of just six, one-hour sessions.

Research is also a big part of the program, McRae said. To that end, she and the team are collecting data on how the model functions, including who benefits most, how referrals happen, what interventions are feasible, and whether the approach is sustainable.

“This is the first time anybody has tried to integrate psychology into pediatric neurosurgery like this,” Rocque said. “So there are so many questions that we need to answer.”

That includes developing screening tools to identify which families need support most urgently and tracking service metrics to ensure the model can be replicated.

“We really want to show that this works,” Rocque said.

Early signs suggest it is. The model has already been adopted in other specialty clinics, including tuberous sclerosis.

“Ideally,” Rocque said, “I would love for this to become the standard of care in pediatric neurosurgery.”

February 17, 2026 by
Neurology & Neurosurgery

An endoscopic approach for skull base conditions

Dr. Jessica Grayson (left) and Dr. James Johnston perform an endoscopic procedure on a patient at Children’s of Alabama.

A growing number of children with complex skull base conditions can now be treated with minimally invasive surgery at Children’s of Alabama thanks to a collaboration between pediatric neurosurgeon James M. Johnston, M.D. and otolaryngologist Jessica Grayson, M.D. Together, they lead an integrated pediatric skull base surgery program that offers endoscopic procedures for conditions such as skull base tumors, traumatic injuries, complex pituitary lesions, and congenital abnormalities such as encephaloceles—in which brain tissue protrudes through an opening in the skull.

“Endoscopic approaches have been part of pediatric neurosurgery here for years for things like hydrocephalus or intraventricular tumors,” said Johnston, director of the Division of Pediatric Neurosurgery at Children’s and the University of Alabama at Birmingham (UAB). “What’s new and exciting is how we’ve expanded endonasal skull base surgery through this collaboration.”

The procedure involves threading a tiny camera and instruments through the patient’s nasal passages to reach the brain. “That means smaller incisions, less blood loss and a much shorter recovery time,” said Grayson—one of the few clinicians in the country who is fellowship trained in rhinology and skull base surgery for both adults and children, with extensive expertise in endoscopic endonasal surgery.

After tumor removal, Grayson works to patch any small holes created between the brain and the nose. This is one of the most critical aspects after the removal—if the small holes aren’t properly sealed, cerebral spinal fluid could leak out into the nose, leading to a high risk of infection. Grayson typically uses a nasoseptal flap to close any openings. She peels a small piece of the mucosa covering the nasal septum while maintaining its blood supply, then flips it over to cover any holes created during surgery.

The program is multidisciplinary, involving ENT, neurosurgery and occasionally plastic surgery. The team-based model also allows for comprehensive case review and planning. “We often consult with our adult colleagues at UAB when a case is really complex,” Johnston said. “It’s like having a built-in tumor board.”

Offering this type of approach for children is another way the program is unique—this method typically has been reserved for adults. And “the technical aspects are different from adult cases,” given their smaller anatomy and less-developed sinuses, Johnston noted. “But with collaboration, it’s absolutely feasible. We’ve even done this in infants as young as a few months old.”

The first collaboration—a case of congenital encephalocele in which the protruding tissue was initially mistaken for adenoid tissue—highlighted the potential of combining expertise. “That was the moment we realized we could safely and effectively treat these cases together using a minimally invasive endoscopic approach,” Grayson said.

Nationally, this type of program is rare. “In many places, kids are sent to adult hospitals for these procedures,” Grayson said. “Here, they can stay in a pediatric environment with pediatric anesthesiologists, nurses and postoperative care, which is crucial for safety and comfort.”

Last year, the team did about 40 cases, and the number of referrals is growing as more clinicians become aware of what’s possible. “We’re seeing more cases from outside hospitals,” Johnston said. “And we’re better at recognizing which patients are good candidates.”

July 30, 2025 by
Neurology & Neurosurgery

Zebrafish model shows potential XMEA treatments

A study in zebrafish of the ultra-rare disease XMEA could help researchers discover treatments. (Stock photo)

By Jeff Hansen, UAB

Can a small fish help identify possible treatments for an ultra-rare inherited disease found in an Alabama boy? The genetic disease is XMEA, which progressively weakens the muscles and can affect the liver and heart. As of March 2024, only 33 cases had ever been seen worldwide.

After the DNA sequence of the boy’s genome showed a mutation in the VMA21 gene, one of the known causes of XMEA, University of Alabama at Birmingham and Children’s of Alabama pediatric neurologist Michael Lopez, M.D., Ph.D., referred the family to the UAB Center for Precision Animal Modeling, or C-PAM.

At C-PAM and in collaboration with a Canadian group, research led by Matthew Alexander, Ph.D., UAB Department of Pediatrics, Division of Pediatric Neurology, and Jim Dowling, M.D., Ph.D., Hospital for Sick Children, Toronto, Ontario, created a preclinical model of XMEA in zebrafish by mutating the fish gene that is analogous to VMA21. While this small, striped fish is commonly found in home aquariums, zebrafish also are a valuable animal model for human disease due to fast growth, large clutch sizes and easy genetic manipulation. They also are transparent as larvae.

Matthew Alexander, Ph.D.

In a study published in EMBO Molecular Medicine, Alexander and Dowling now show that their mutant zebrafish have weakened muscles and other symptoms that mirror human XMEA disease. With this simple model, they were able to test 30 clinically tested drugs and identify two that significantly improved XMEA symptoms in the zebrafish. They now are studying the VMA21 mutation in a mammalian model, the mouse, to further push research toward a possible clinical treatment.

“We have established the first preclinical animal model of XMEA, and we have determined that this model faithfully recapitulates most features of the human disease,” Alexander said. “It thus is ideally suited for establishing disease pathomechanisms and identifying therapies.”

Researchers used CRISPR-Cas9, often called molecular scissors for DNA, to create two mutants: a frameshift mutation caused by a one-base pair deletion, and a premature stop codon created during deletion of 14 base pairs and insertion of 21. Both loss-of-function mutations reduced VMA21 protein levels.

Both mutants showed changes consistent with altered muscle structure and function, such as shorter body length and non-inflated swim bladders. They had reduced ability to swim away from a stimulus, and they spent less time swimming and traveled less distance compared to wildtype zebrafish.

The key cellular change in human XMEA is impairment of autophagy, the cell’s recycling system. Autophagy takes place in cell organelles called lysosomes, and these need to be acidic to activate proteases that degrade proteins for recycling into new proteins. Like human XMEA, the mutant fish lysosomes showed a failure to acidify, and the muscle cells had characteristic vacuoles — fluid-filled enclosed structures. Like human XMEA patients, the fish also showed liver and heart pathologies.

Unlike human XMEA, which can vary from mild to moderate symptoms as a progressive disease, the mutant fish showed severe reductions in life span, presumably due to a more complete loss of VMA function compared to human patients.

Since the fish had impaired autophagy and since there are no therapies for XMEA patients, the researchers tested 30 clinically tested autophagy inhibitory compounds from the Selleckchem drug library on the XMEA fish.

Screening of clutches for changed muscle birefringence, a change in the refraction of polarized light that indicates reduced muscle organization, the team identified nine compounds that both reduced abnormal birefringence and prolonged fish survival. Long-term testing of the nine for improvements in survival and swimming showed that edaravone and LY294002 had the greatest therapeutic effects.

“Excitingly, we found that several autophagy antagonists could ameliorate aspects of the VMA21 zebrafish phenotype, and two compounds in particular improved the phenotype across multiple domains of birefringence, motor function and survival,” Alexander said. “The fact that multiple autophagy modulators ameliorated aspects of the phenotype supports an important role for autophagy in the disease process and lends confidence to the validity and potential translatability of the findings to patients.”

Co-authors with Alexander and Dowling in the study “X-linked myopathy with excessive autophagy: characterization and therapy testing in a zebrafish model,” are Lily Huang, Rebecca Simonian and Lacramioara Fabian, Hospital for Sick Children; and Michael A. Lopez, Muthukumar Karuppasamy, Veronica M. Sanders and Katherine G. English, UAB Department of Pediatrics, Division of Pediatric Neurology.

At UAB, Pediatrics is a department in the Marnix E. Heersink School of Medicine.

XMEA stands for X-linked myopathy with excessive autophagy.

July 25, 2025 by
Neurology & Neurosurgery

Children’s of Alabama Offering New Gene Therapy for Patients With DMD

A new treatment offers the hope of longer, better life for DMD patients. (Stock photo)

In January 2025, Children’s of Alabama, for the first time, treated a patient with Duchenne muscular dystrophy (DMD) using a new gene therapy offered by only a few academic hospital facilities in the nation. The milestone followed a lengthy approval process and marked a new opportunity for patient success and scientific progress. Though not a cure, the treatment represents the hope of a longer life for these patients. For researchers, it will contribute to greater learning about the potential of this new treatment.

What is DMD?

While it is considered a rare disease, DMD is the most common form of muscular dystrophy, affecting one in every 5,000 males born in the United States. Patients experience progressive muscle degeneration, starting with proximal muscles and expanding to the limbs over time. They have trouble with many physical activities such as jumping, running and walking, and lose the ability to walk over time. The disease is fatal, and most patients don’t live past their late 20s. DMD has no cure; treatment focuses on extending the patient’s life by slowing down the disease’s progression.

According to the Muscular Dystrophy Association, symptoms of DMD can begin as early as ages 2-3 years, but in Alabama, where DMD is not yet part of newborn screening, many boys are not diagnosed until ages 4-6. That, says Children’s neuromuscular nurse practitioner Samantha Weaver, DNP, CRNP, is when patients begin to experience a steady decline. 

Treatment

Since the 1990s, physicians have prolonged the lives of patients with DMD using corticosteroids, whose anti-inflammatory properties can slow down the disease’s progression by about three years. Gene therapy, however, represents a new treatment aimed at restoring the function of the causative gene, DYSTROPHIN. The U.S. Food and Drug Administration originally approved it in 2023 for use in patients ages 4-5. In 2024, the agency extended that approval to all patients 4 years and older.

In this treatment, the transgene (a micro-DYSTROPHIN synthetic gene) is packaged within a viral capsid—a virus not intended to harm the patient that can hold the genetic material. In essence, physicians are “giving back the missing genetic information to the muscle tissue,” Children’s neurologist Michael Lopez, M.D., Ph.D., said. Unlike any other option, he noted, gene therapy treats the root cause of DMD.

“Now that we’re starting to get these really breakthrough therapies, they’re fulfilling on the promise that we all were searching for, which is that we could get closer to making this disease really better,” he said.

For the patient, improvements don’t happen overnight. That’s not how gene therapy works, Lopez says. “What we hope is that over many years, we’ll see a slow progression of the disease that is beyond what we would get with just treatment with corticosteroids alone,” he explained. “And I think that added benefit is something that’s going to be more of a long-term improvement.”

So, what can the parents of each patient treated with gene therapy hope to see? Ideally, in the short-term, their child will be more active. “I hope that our children can have more of a shot at more play and more jumping and more climbing and all of those things in the future,” said Erin McLeod, M.D., a pediatric neuromuscular neurologist at Children’s. In the long-term, the hope is that they’ll have a longer life.

Evidence supports the treatment’s efficacy. The clinical trials show that gene therapy is being delivered to patient’s muscles, and while the motor assessments haven’t shown clear evidence of clinically observable benefits, the data has trended toward improvement. Lopez says in other, more-recent studies, treated patients are starting to show improvements compared to those not receiving gene therapy. “The MRIs of the muscles themselves look a little bit healthier in some of these patients,” he said. “There’s less evidence of disease in that.”

From left: Samantha Weaver, DNP, CRNP; Erin McLeod, M.D.; Michael Lopez, M.D., Ph.D.

Finding the Right Fit

Gene therapy, however, is not the right fit for every patient. To determine candidates, Children’s looks at age, underlying disease and disease progression, Weaver said. They also consider the patient’s overall health and risk for infectious diseases. “It’s an extensive process,” she explained.

With all gene therapies, safety must be prioritized. The treatment can produce a significant immune response that can even prove life-threatening to patients with more advanced stages of the disease. Liver injury is also a major concern. Thus, Weaver says the team must ensure the patient has no antibodies that will reject the virus. “These are important steps to make sure the patient will have the best outcome,” she said.

Because of these considerations, only a small percentage of patients are ideal for the treatment.

Why Offer it at Children’s?

In Alabama, Children’s is the only hospital that offers gene therapy for patients with DMD. Making it available made sense—the hospital already treats spinal muscular atrophy (SMA) patients with gene therapy. Brad Troxler, M.D., and Shelley Coskery, CRNP, led the way on that, Lopez said, and “built in a lot of the infrastructure that we needed to be able to start doing gene therapies.”

“That really has put us out in front of the field with the experience to deliver these high-cost and novel leading-edge treatments,” he added.

Challenges

Cost was one of many challenges for the team as they sought approval to implement this multimillion-dollar therapy. To that end, they involved hospital administration and a pharmacoeconomics committee in the process. But, as Weaver pointed out, the process involved many more steps including determining who would write a protocol to ensure patient safety. They also had to build a larger team, which ultimately included hepatologists, pulmonologists, cardiologists, physical therapists and social workers.

Obstacles persist, even as Children’s offers the treatment. “A high cost remains a big challenge,” Lopez said. “And so we’ve been fortunate to be able to provide these treatments because we’ve gotten support from the insurers, so far.” But not every insurer is the same, he noted, and some may be slow to cover or even decline to cover the treatment.

What the Future Holds

So far, Children’s has dosed only one patient—out of roughly 100 that it follows—with the new gene therapy. While few will be candidates for the treatment, the team hopes to dose more in the future, as long as “the risk is appropriate and the benefit is continuing to be demonstrated,” Lopez said. The team also expects more advancements, which may make it possible for others—especially those with more severe cases—to receive the treatment.

“This first approved treatment for Duchenne that is a gene therapy is just the beginning, and there are going to be more down the road,” Lopez added. “There are certainly some that are in clinical trials now. So I think we’re right to be optimistic in that we’re starting to really push the treatment of Duchenne in a way that’s going to give us lots of options that weren’t there before.”

And as Children’s continues to offer the treatment, they’ll contribute to the scientific community’s information on its effectiveness, which means the team is paving the way toward greater success for the broader population of patients with DMD.

“I think everyone who is familiar with it at this point knows it is not a cure. But it is supposed to significantly slow the disease, and we are still gathering and gaining more data to that,” Weaver said. “So we’re very excited to be part of that process.”

July 25, 2025 by
Neurology & Neurosurgery

New MEG at UAB to enhance neuroimaging possibilities 

A new magnetoencephalography could improve treatment of multiple brain diseases at UAB and Children’s. (Photo by Andrea Mabry)

By Katherine Gaither, UAB

The complexity of the human brain has long been an enigma that neuroscientists have sought to untangle. Now, new technology at UAB will act as a critical tool to help researchers and clinicians interpret the brain in unprecedented ways.

UAB has recently invested in a new MEG, which stands for magnetoencephalography. It is used on pediatric and adult patients, so it benefits patients at both UAB and Children’s of Alabama. Put simply, MEG technology measures the magnetic fields that come from the brain’s nerve cells in an effort to analyze their function—and does so at millisecond intervals.

These implications are significant not only for localizing abnormalities in the brain in patients with diseases like epilepsy but also for studying how the brain performs normal functions like speaking, hearing, and seeing.

“It’s not invasive,” said Ismail Mohamed, M.D., professor in the UAB Division of Pediatric Neurology, Department of Pediatrics. “You don’t have to put electrodes in the brain, and it has no risks. You can potentially measure brain activity across multiple sessions. You can potentially measure them across a lifetime span. You can use it to learn things about how our brain functions.”

Measuring the brain’s magnetic fields

UAB was among the first medical centers in the country to obtain a MEG, having done so originally in 2001; however, evolving technology has created a need for replacing the old technology with a new one. The new machine was installed in September 2024.

Many are familiar with MRI as a form of imaging to interpret brain activity; however, having a MEG is not as common. UAB is one of fewer than 30 clinical centers in the nation that houses this technology.

“MRI looks at structure, but MEG primarily looks at the brain waves itself,” Mohamed explained.

The machine operates in a sealed room with a thick door, which eliminates outside magnetic noise. Patients lie or sit still during the scan, which takes precise magnetic field measurements of brain activity.

“The experience is not much different from laying inside an MRI scanner; however, the technology is quite different, and the way we measure is quite different,” Mohamed said. “It’s a passive measurement, which means that even if you’re pregnant, for example, you still can get a MEG scan. There are no risks.”

Compared to MRI and other brain scans like PET, and SPECT, the MEG gives you unique information about the brain as it tracks the activity of the nerve cells. EEG scans are similar, but the MEG has a heightened ability to localize this activity.

“A traditional EEG uses 25 electrodes. The MEG has 306 sensors,” Mohamed said. “So that coverage of the brain is bigger, it enhances the potential to produce more accurate information.”

According to Benjamin Cox, M.D., assistant professor in the UAB Department of Neurology, the difference is also electric vs. magnetic.

“The electrical fields that EEGs are recording are very much attenuated by the skull and all the intervening tissues,” Cox said. “The magnetic fields are not. So, we get a lot more precise localization with the MEG.”

Clinical implications

One significant implementation of the MEG is for use in epilepsy surgery to determine where in the brain seizures originate. Surgeons can use the results of a MEG scan to plan epilepsy surgeries.

“When we’re doing epilepsy surgery and trying to figure out if patients are a surgery candidate, we need to know exactly where the seizures are coming from as precisely as possible, and many times we end up putting electrodes in the brain to sample that activity directly,” Cox said. “So having studies like MEG, where we can have a precise idea of where to put those electrodes, is very helpful.”

Kristen Riley, M.D., professor in the UAB Department of Neurosurgery, notes that “MEG studies help us as surgeons to localize seizure onset zones, directing us to areas to implant monitoring electrodes. Often these areas look completely normal on MRI, but are identified by the MEG study as possible sites of seizure onset.”

A second clinical implementation involves functional brain mapping—to localize areas important for language, sensory and motor function.

“It has huge implications for learning, like child development,” Mohamed said. “Learning new languages. Processing information as the child grows. It also has a lot of potential research use for the prediction of disease outcomes. Studying things like dementia or Alzheimer’s disease.”

Cox added that the new MEG’s presence within UAB Hospital creates advantages for patients and clinicians when used as an inpatient procedure instead of an outpatient procedure, as it has been in the past.

“Epilepsy patients are on seizure medicines on a day-to-day basis to prevent seizures from happening,” Cox said. “When we bring them into the hospital and evaluate them for surgery, we get them off of their medicines, which increases epileptic activity in the brain, so it will hopefully increase the likelihood we record epileptic activity during the MEG scan.”

Studying epilepsy less invasively

From a research perspective, Rachel Smith, Ph.D., assistant professor in the UAB Department of Electrical and Computer Engineering, had been using the existing MEG to validate methods that she has been developing for intracranial EEG in epilepsy patients through a project funded by CURE Epilepsy.

“We’re electrically stimulating a given brain region and then looking for responses in the rest of the brain,” Smith explained. “That is helping us build these unique brain networks. So, we know if we stimulated in one region and see a response in another region, that means that those two regions are likely functionally or anatomically connected in some way.”

Smith and her team are then using MEG data to build computer models that can hopefully test neurophysiological signals virtually to localize epileptic seizures—and therefore less invasively.

“We’re actually saying, let’s build a network from MEG data and see if we can do a virtual stimulation where we actually just stimulate in the computer model and not in real life and see if we can get the same clinical information out,” Smith added.

The new MEG will be a useful tool for advancing research into the future; however, researchers are already realizing significant research implications with the new technology.

“It’s going to be really helpful and translational for a lot of patients right now,” Smith said. “I think being one of 27 centers across the U.S. that has access to this in our hospital is a huge opportunity for people here at UAB to take advantage of. We’re really excited.”

January 21, 2025 by
Neurology & Neurosurgery

Procedure and device offer new options for epilepsy patients

Curtis Rozzelle, M.D., performing a deep brain stimulation procedure for epilepsy.

In January 2024, a University of Alabama at Birmingham (UAB) pediatric neurosurgeon performed the first deep brain stimulation (DBS) procedure for epilepsy at Children’s of Alabama, offering a new treatment option for pediatric patients who experience drug-resistant seizures.

During the procedure, Curtis J. Rozzelle, M.D., a professor in the UAB Department of Neurosurgery, also implanted the first NeuroPace responsive neurostimulation (RNS) epilepsy treatment device at Children’s.

The NeuroPace RNS ® System, which consists of a small generator attached by leads to electrodes, was designed to communicate with a computer to record brain activity, recognize seizure-related patterns and deliver stimulation to suppress seizures. The device, which is curved for better placement within the skull, monitors brainwaves constantly and can be customized on a patient-by-patient basis.

“Much like a cardiac pacemaker that senses and responds to abnormal heart rhythms, this combination of technologies will detect brain activity that precedes seizures, then stimulate pathways deep in the brain to either prevent seizures from starting or stop seizure activity in its tracks,” Rozzelle said.

When performing a DBS procedure, a neurosurgeon inserts electrodes connected to a neurostimulator into the brain to disrupt epileptic electrical activity before it can cause a seizure. Similar to the RNS System, the DBS neuromodulation device can be programmed after placement in an outpatient clinic by an epilepsy specialist, like UAB Department of Pediatrics Division of Neurology professor Monisha Goyal, M.D.

In this case, Rozzelle placed the RNS® System electrodes in the thalamus, resulting in a twofold RNS and DBS procedure. 

Neurostimulators have long been used to treat various neurological disorders when traditional treatment options fail. DBS was originally developed in 1997 to treat Parkinson’s disease and has since expanded as a treatment option for epilepsy, dystonia and more. RNS gained initial FDA approval in 2013 and has proved to be effective in many patients. Presently, RNS is FDA-approved only for adults, but is successfully being used off label in the pediatric population.

Though DBS and RNS are not viable options for all patients, they show tremendous potential in treating children with epilepsy who need more innovative treatment options. “With this first RNS implantation [at Children’s of Alabama], we have expanded the armamentarium of therapies available to individuals with poorly controlled epilepsy,” Goyal said. “Unfortunately, neuromodulation with RNS is only [FDA-approved] for individuals who are at least 18 years old. The pediatric epilepsy team at Children’s of Alabama hopes that this therapy will be available to more children of Alabama soon.”

August 9, 2024 by
Neurology & Neurosurgery

Deep brain stimulation for progressive dystonia

In 2023, Children’s of Alabama performed deep brain stimulation on progressive dystonia patients for the first time.

Progressive dystonia disorders, characterized by changes in movement patterns, can profoundly impact a child’s quality of life. In adults, such disorders are routinely treated with a procedure called deep brain stimulation (DBS). However, this intervention is less commonly used in pediatric populations.

In 2023, Curtis Rozzelle, M.D., and Emily Gantz, M.D., performed Children’s of Alabama’s first DBS procedures for progressive dystonia patients. This innovative therapy has shown promising results in several pediatric patients with limited treatment options.

Curtis Rozzelle, M.D.

“We’re excited that this innovative procedure is now transferring over to our pediatric patients,” Rozzelle, a pediatric neurosurgeon at Children’s, said. “Kids with progressive dystonia seem to do particularly well, while those with other types of movement disorders may have mixed results.”

Studies suggest that pediatric patients with progressive dystonia respond well to deep brain stimulation, especially after failing conventional medications. The decision to apply DBS in pediatric cases stems from the specific needs of young patients and advancements in the field.

“Until Dr. Gantz arrived at the University of Alabama at Birmingham, we didn’t have a movement disorder neurologist here who also had training and experience with deep brain stimulation,” Rozzelle said. “When she arrived, Dr. Gantz opened the door for us to be able to perform the technical aspects of the surgical procedure. Now, we’ve done several.”

Not every child is an ideal candidate for DBS. The decision to initiate DBS is patient-specific, based on the severity of symptoms and the inadequacy of other treatments. A careful evaluation of each patient’s unique situation, including factors such as genetic mutations and the progression of the disease, must be completed before offering DBS surgery.

Each deep brain stimulation procedure at Children’s uses stereotactic surgical techniques and the ClearPoint targeting system. This system, employed in an MRI scanner, ensures safe, precise electrode placement in the globus pallidus interna (GPI), a key target for treating progressive dystonia.

Emily Gantz, M.D.

“When we implant the electrode into a specific region of the brain, we can either edit the input throughout the stimulation, or we can take it completely away,” Gantz said. “Think of it as a series of relay circuits in the brain. If someone has dystonia, one of those relay circuits isn’t working properly. By putting in the stimulator and applying an electrical current intermittently, we can suppress the abnormal brain activity.

“The stimulator stays in for life, so the procedure doesn’t need to be repeated,” she continued. “Occasionally, we’ll have to change the device’s battery, but they’re rechargeable and designed to last for up to 20 years.”

After the initial procedure, patients return to see Gantz to have the device programmed. “I set the programming on their stimulator so they can make slight adjustments at home. It can take a little while for the device to be effective; we usually leave it alone for a few months and then reevaluate,” Gantz said. “We have guidelines for which settings will most likely help, and we start there. We’re looking to ensure we don’t get side effects, such as visual disturbances or muscle pulling, more than anything.”

The pediatric patients who have begun DBS for progressive dystonia at Children’s are responding well to the new treatment. “I’m really excited about DBS and its future as a treatment in pediatric neurology, specifically movement disorders,” Gantz said. “It may eventually come into play in other treatment areas, and I’m glad the door is open to us here. I think there will be many more patients who will benefit from it.”

January 30, 2024 by