Researchers from the Universities of Edinburgh and Oxford have identified terazosin, a medication historically used for prostatitis and high blood pressure, as a potential protector of the nervous system against motor neuron disease (MND). The study, published in EBioMedicine, highlights a possible new avenue for delaying the progression of a condition where motor neurons deteriorate and patients typically face a rapid decline within a few years after symptoms begin.
Terazosin’s prior hints of neuroprotective effects came from its ability to boost cellular energy production in models of stroke and Parkinson’s disease. In this new work, scientists explored whether increasing energy capacity could also shield brain and spinal cord neurons from MND. A key focus was the enzyme PGK1, whose activity is increased by terazosin. PGK1 is a pivotal player in cellular energy generation, transforming energy currencies within cells to power essential processes. By modeling MND in zebrafish, the researchers demonstrated that boosting PGK1 levels in genetically modified fish, along with administering terazosin, led to improved survival outcomes and a slower trajectory of motor impairment in the disease model.
Complementary experiments were performed with human motor neurons cultivated in vitro. In these cell culture studies, terazosin appeared to preserve neuron health by elevating energy reserves, suggesting that neurons might better withstand the metabolic stress associated with MND when energy production is enhanced by the drug.
MND comprises a group of rare disorders characterized by selective loss of motor neurons, resulting in progressive weakness and eventual paralysis. A common early feature is diminished neuronal energy production, which hampers the ability of neurons to relay signals to muscles. When energy delivery falters, the neuromuscular system struggles to maintain movement and coordination, accelerating disability in patients.
Building on these mechanistic insights, the research team has initiated a feasibility study involving fifty individuals diagnosed with MND to evaluate terazosin’s safety and tolerability in this patient population. The study will monitor key indicators of disease progression, including measures of motor function, respiratory capacity, and activities of daily living, to determine whether the drug can meaningfully slow the course of the disease. Should the feasibility results be favorable, plans are in place to advance into a full-scale clinical trial to robustly test terazosin’s therapeutic potential in MND, ideally in combination with other supportive therapies and lifestyle interventions that support neuronal resilience. (Source attribution: University of Edinburgh and University of Oxford researchers, 2024.)