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Common ADHD medication may provide insight into other ways to treat this and other neuromuscular diseases

Using a common attention deficit hyperactivity disorder (ADHD) medication appears to help manage the symptoms of a rare and currently difficult to treat genetic movement disorder primarily found in children, according to a new study from a University of Maryland School of BOB体育 (UMSOM) researcher Andrea Meredith, PhD, and her collaborators.

The disorder, KCNMA1-linked channelopathy, named after the affected gene, can cause abnormal, involuntary movements from collapsing episodes, in which patients slump forward with their arms and legs appearing rigid. These episodes can occur up to 300 times per day, putting patients at risk of serious injury.

The researcher found that the stimulant drug, lisdexamfetamine, reduced these attacks and may help other accompanying symptoms, such as seizures and developmental delays, as well.

These findings were published online on December 11, 2021 in .

The researchers say their findings can help to better understand different brain regions involved with the attacks and how the disease manifests itself. While this research shows promise of specifically treating KCNMA1-linked channelopathy, there are broader implications to exploring the treatment effects on the body, potentially shedding light on the mechanisms behind other neuromuscular diseases and how to treat them.

鈥淪ometimes the science doesn鈥檛 initially lead us to the answers, it is often the patients and families themselves,鈥� said senior author Dr. Meredith, Professor of Physiology at the University of Maryland School of BOB体育.

Only about 75 people so far have been identified worldwide with this disorder which was identified as recently as 2005. A major advance came in 2019 when it was reported anecdotally that a child suffering from the disorder was prescribed lisdexamfetamine by their neurologist, which according to the family seemed to help. The physician tried this stimulant medication, commonly used to treat cataplexy-related disorders; the child鈥檚 symptoms resembled cataplexy, which is a sudden muscle weakness without losing consciousness. From there, word spread to other families over social media, news media, and the disease鈥檚 advocacy foundation, KCNMA1 Channelopathy International Advocacy Foundation, that was co-founded by Dr. Meredith. The buzz from the patients鈥� families spurred neurologists, including the study authors, to test the relatively safe drug that is approved by the U.S. Food and Drug Administration to treat ADHD.

For their study, the researchers analyzed reports of six patients treated with lisdexamfetamine. They found that the collapsing episodes were reduced by about 10-fold or were completely resolved in four patients. Most patients also showed improvements in speech, school performance, concentration, and social skills, all of which can affect patients with this disease as well. None of the patients experienced seizures during the study period. The most common side effect reported was loss of appetite and difficulty sleeping.

鈥淔rom the anecdotal reports we already had, we weren鈥檛 particularly surprised by these findings,鈥� said Dr. Meredith. 鈥淏ut gathering the real-world evidence that the drug is actually working to treat the symptoms is important for clinicians who may prescribe the drug to officially diagnosed patients.鈥�

It is currently unclear how lisdexamfetamine works to treat the attacks. The gene affected in the disorder, KCNMA1, encodes a protein that makes a 鈥榗hannel鈥� in brain and muscle cells. This channel lets potassium out of the cell to change its electric charge. Neurons in the brain send messages and tell the muscles to move using these electrical signals, but the exact way this channel disruption leads to the symptoms experienced by the patients is unknown.

However, the success of lisdexamfetamine treatment in the small group of patients may provide the answers. 鈥淲e have exciting mechanistic avenues to pursue as a result of this finding,鈥� said Dr. Meredith. 鈥淲e do know that the drug does not directly affect the activity of the channels, so we think the drug has either a separate, or an indirect effect, on the channels.鈥�

They researchers plan to continue studies of the disorder and the drug in their mouse models.

鈥淩are diseases are often overlooked in research and treatment ,鈥� said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of BOB体育. "We are proud of our researchers in pursuing treatment of a rare disease that opens new doors, pushes medical boundaries, and improves the lives of those who may feel left behind.鈥�

Other authors on the study included , and , of Weill Cornell Medical College; , Wejdan Hakami, and , of Phoenix Children's Hospital; and Efrat Zohar-Dayan and , of Chaim Sheba Medical Center, Israel.

Dr. Meredith鈥檚 research is supported by grants from the National Heart, Lung, and Blood Institute (R01-HL102758), the National Institute of General Medical Sciences (T32-GM008181), and the S&R Foundation Ryuji Ueno Award for Ion Channels Research (The American Physiological Society).

Dr. Keros, Dr. Meredith, and Dr. Kruer are uncompensated officers of the non-profit KCNMA1 Channelopathy International Advocacy Foundation. The authors declare no conflicts of interest related to this work.

About the University of Maryland School of BOB体育

Now in its third century, the University of Maryland School of BOB体育 was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of BOB体育 and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of BOB体育 works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of BOB体育 has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of BOB体育 has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of BOB体育 and Medical System (鈥淯niversity of Maryland BOB体育鈥�) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of BOB体育, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of BOB体育 is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of BOB体育 works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu