Updated: December 13, 2020 6:19 PM IST
Washington [US], Dec 13 (ANI): A new study suggests that the drug ezogabine “> drug”> antiepileptic drug ezogabine reduced the pathological excitability of cortical and spinal motor neuron cells that are early signs of clinical dysfunction in people with amyotrophic lateral sclerosis (THE A) .
The study was conducted by the Massachusetts General Hospital (MGH) Clinical Neurological Research Institute.
In addition to providing a clearer understanding of motor neuron excitability as an important disease pathway for ALS, the multi-site study, published in JAMA Neurology, involves the first clinical investigation of ALS (also known as Lou’s disease). Gehrig) using a drug identified through an induced pluripotent stem cell (iPSC) model.
“The stem cell approach allowed us to capture motor neuron hyperexcitability, a prominent disease phenotype, and then show that ezogabine was able to reduce it in people with ALS,” said lead author Brian Wainger, MD, PhD, of the Healey Center for ALS at MGH.
“Our findings could have important implications for the field of ALS research by demonstrating the effect of ezogabine on excitability in people with the disease and by showing that cortical and spinal motor neuron excitability metrics can be used as biomarkers. of drugs in multi-site clinical trials, “Wainger added.
ALS is a progressive neurodegenerative disorder that leads to the death of neurons in the brain and spinal cord that control speech, swallowing, and limb movements.
Named after famous baseball player Lou Gehrig, who was diagnosed with the disease in 1939, there are about 20,000 people in the US with ALS and another 5,000 newly diagnosed cases each year.
Currently, there are three drugs approved in the US to treat ALS, each with limited benefit, creating an urgent need for new therapies that could change the course of the deadly disease.
The MGH study of ezogabine was not designed to evaluate the long-term effects of the drug in neurodegenerative disorder, but rather to unravel biological processes that go wrong and identify new molecular targets for drug intervention.
To that end, the 10-week phase 2 study of 65 participants with ALS at 12 US sites investigated the feasibility of using neuronal excitability metrics as predictors of disease progression.
“We demonstrated for the first time that these neurophysiological trials can be implemented effectively across multiple study sites, which is important in disease trials like ALS where researchers depend on many sites for recruitment,” Wainger said.
“That finding could be useful for evaluating other drugs to treat ALS, or even for other diseases where motor neuron metrics could serve as key biomarkers,” Wainger added.
Ezogabine (also known as retigabine) had previously been approved by the United States Food and Drug Administration (FDA) to treat epilepsy with a unique mechanism of action: facilitating potassium channels in cell membranes that play a role. central in the control of neuronal excitability, particularly important in the control of seizures.
Researchers at the MGH Clinical Neurological Research Institute began to evaluate the drug’s potential in the context of ALS, using transcranial magnetic stimulation (TMS) and threshold follow-up nerve conduction studies (TTNCS) to measure the effects of ezogabine on the excitability of motor neurons. They found that ezogabine calmed the excitability of motor neurons.
“More studies are needed to determine whether longer treatment will maintain the effects of reduced excitability and, if so, whether that can slow the progression of the disease,” Wainger said.
“Through our study, we hope to have established a new research paradigm for using iPSC-based in vitro models to identify new disease targets and compounds, and rapidly reuse drugs for clinical trials,” Wainger added. (AND ME)