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Home NEWS Science News

University of Cincinnati experts present at national neurology conference

Bioengineer by Bioengineer
April 12, 2024
in Science News
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University of Cincinnati researchers will present abstracts at the American Academy of Neurology annual meeting 2024, April 13-18 in Denver, Colorado.

Alberto Espay, MD

Credit: Photo/University of Cincinnati.

University of Cincinnati researchers will present abstracts at the American Academy of Neurology annual meeting 2024, April 13-18 in Denver, Colorado.

Two-component treatment leads to improvement for patients

Late-onset Pompe disease (LOPD) is a rare, inherited genetic disease caused by the accumulation of glycogen, the body’s stored form of glucose, in muscles and other organs. Left untreated, the muscle weakness it causes can lead to the loss of the ability to walk and breathing impairment.

A research team led by UC’s Hani Kushlaf, MD, looked at the effect of a two-component enzyme replacement therapy (ERT) of drugs cipaglucosidase and miglustat (cipa+mig) compared to a single ERT drug, alglucosidase alfa (alg) and a placebo. UC researchers participated in the Phase 3 trials that led to the Food and Drug Administration approval of both ERT regimens.

“The research question was to look at the magnitude and practical significance of the effect of cip+mig versus alg using patient data from the PROPEL trial on outcomes that included motor function, pulmonary function, muscle strength, biomarkers and patient- and physician-reported quality of life,” said Kushlaf, associate professor and director of Neuromuscular Research and the Neuromuscular Disorders Division in UC’s Department of Neurology & Rehabilitation Medicine in the College of Medicine.

Patients who switched to the dual ERT regimen experienced improvement or stability across the measured outcomes with no worsening of outcomes. Those who remained on the single ERT drug plus placebo experienced worsening or stability across the measured outcomes.

“This analysis highlights the potential of cipaglucosidase+miglustat to become an important treatment option for patients with LOPD, including patients already on enzyme replacement therapy,” Kushlaf said.

This research was sponsored by Amicus Therapeutics, Inc.

Research team learns more about events following immunotherapy treatment 

Immune checkpoint inhibitors (ICIs), an immunotherapy that activates the body’s immune system to fight cancer cells, has revolutionized cancer treatment. But while boosting anti-tumor immunity, the treatments may cause severe neurological-immune related adverse events. 

“These neurological-immune-related adverse events include meningitis, encephalitis, demyelinating diseases, vasculitis, neuropathy, neuromuscular junction disorders and myopathy,” said Luca Marsili, MD, PhD, movement disorder fellow in the Department of Neurology and Rehabilitation Medicine in the University of Cincinnati College of Medicine.  

Marsili said the frequency of these adverse events, and the best way to manage them, is still largely unknown. 

A team led by Marsili and Alberto Espay, MD, reviewed reported neurological-immune-related adverse events in patients treated with immune checkpoint inhibitors at UC from 2011-2023. They found the adverse events are rare, affecting 28 patients out of 1,677 treated, or 1.66%. 

The adverse events were most often associated with melanoma treatment with pembrolizumab, a common immunotherapy treatment. 

“The adverse events were most expressed as peripheral neuropathies and encephalitis, manifesting early during treatment within a mean of 2.3 months after ICI initiation,” Marsili said. “Most ICIs, 68%, were discontinued, and in only 10.7% of cases they were restarted without complications.” 

Moving forward, the team said further research is needed to determine clinical susceptibility factors and appropriate timing of restarting ICI treatment after discontinuing due to an adverse event. They are also planning to do more detailed demographic and clinical comparisons of the 28 patients identified to have adverse events to see if there are any predictive factors like tumor type, age, sex or ethnicity. 

“This study is part of a broader project in collaboration with the University of Udine in Italy and with the Department of Internal Medicine at UC,” Marsili said. “We would like to gather a high number of participants to assess incidence/prevalence of these adverse events and also to raise awareness among neurologists on how to treat/manage them.” 

Safe, effective treatment for Parkinson’s 

Alberto Espay, MD, will present findings recently published in the Lancet Neurology journal that found Parkinson’s disease medication delivered through an infusion pump is safe and effective at reducing symptoms for longer periods of time. 

Parkinson’s symptoms such as tremors, slowness and stiffness are caused by low levels of dopamine in the body. For decades, doctors have treated Parkinson’s by giving patients levodopa, the inactive substance in the brain that once converted makes dopamine.  

“Levodopa is a replacement strategy. We all make levodopa, but Parkinson’s patients make less of it,” said Espay, co-principal investigator of the trial, the James J. and Joan A. Gardner Family Center for Parkinson’s Disease Research Endowed Chair in UC’s Department of Neurology and Rehabilitation Medicine and a physician at the UC Gardner Neuroscience Institute.  

Levodopa is most commonly administered orally, but this trial tested continuous, 24-hour levodopa delivery through a subcutaneous infusion pump. A total of 381 patients with Parkinson’s disease in 16 countries enrolled in the trial and were randomized to receive levodopa through the infusion pump or through traditional oral medication. 

The researchers found levodopa delivered through the infusion pump was safe and led to almost two hours a day (1.72) of additional “on time,” or the time when the medication is working and symptoms are lessened, compared to taking levodopa orally. 

“Once approved, this will become an important treatment strategy to consider for patients with Parkinson’s disease experiencing motor fluctuations not adequately controlled with medication,” he said. “Future studies will need to determine the durability of the long-term benefits and whether any safety issues could emerge, as well as how it might compare with deep brain stimulation.” 

UC research being presented at AAN includes:

  • Kushlaf presenting “Effect Size Analysis of Cipaglucosidase Alfa Plus Miglustat Versus Alglucosidase Alfa in ERT-experienced Adults with Late-onset Pompe Disease in PROPEL.”
  • Marsili and Espay presenting “Neurological Immune-related Adverse Events of Immune Checkpoint Inhibitors: A Single-center Retrospective Study.” 
  • Espay presenting “Efficacy of ND0612, a 24-hour Subcutaneous Levodopa/Carbidopa Infusion for People with Parkinson’s Disease Experiencing Motor Fluctuations: Subgroup-analyses from a Randomized, Controlled Phase 3 Study.”
  • Stacie Demel, DO, PhD, a physician-researcher at the UC Gardner Neuroscience Institute and associate professor of clinical neurology and rehabilitation medicine in UC’s College of Medicine, presenting “Methylation Patterns Differ Between ICH Cases and Controls.”
  • Yang Yu, MD, UC medical resident/fellow, presenting “Multiple Sclerosis in a Patient with Friedreich’s Ataxia.”
  • Rhonna Shatz, DO, adjunct associate professor, division director for behavioral neurology, and the Bob and Sandy Heimann Endowed Chair in Research and Education in Alzheimer’s Disease in the UC College of Medicine, presenting “Identifying a Relationship Between Executive Dysfunction, Poor Sleep Hygiene/Sleep Apnea, and Ventriculomegaly in Cancer-related Cognitive Impairment (CRCI)”


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