Publications by authors named "J R Forsayeth"

Article Synopsis
  • Alcohol Use Disorder (AUD) leads to significant personal, social, and economic impacts globally, with many patients experiencing cycles of relapse despite treatment.
  • Researchers conducted a study on rhesus monkeys to explore whether infusing a growth factor called GDNF into the brain could prevent relapse after periods of abstinence.
  • The results showed that GDNF not only reduced alcohol use over a year but also improved dopamine signaling in the brain, indicating that gene therapy might be a viable approach for preventing relapse in AUD.
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  • * Interleukin-10 is an anti-inflammatory cytokine that can help reduce these problematic cytokines, but its natural form has a short lifespan and doesn't penetrate joints well, leading to the development of a longer-lasting version delivered via a plasmid DNA-based therapy (hIL-10var).
  • * A 6-month study showed that injections of hIL-10var into dogs with osteoarthritis were safe and well-tolerated, and a small trial indicated that this therapy effectively reduced pain, setting the stage for future
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  • * Researchers tested a method of administering gene therapy (AAV9-hASM) through cerebellomedullary injection in nonhuman primates and a mouse model, finding it to be safe and effective without causing inflammation or toxicity.
  • * This approach showed promise in preventing key symptoms of the disease in mice, including motor and memory issues, and led to reduced harmful compounds in the brain and liver, supporting further clinical testing for treating NPD-A and similar disorders.
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Here we evaluated the utility of MRI to monitor intrathecal infusions in nonhuman primates. Adeno-associated virus (AAV) spiked with gadoteridol, a gadolinium-based MRI contrast agent, enabled real-time visualization of infusions delivered either via cerebromedullary cistern, lumbar, cerebromedullary and lumbar, or intracerebroventricular infusion. The kinetics of vector clearance from the cerebrospinal fluid (CSF) were analyzed.

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The present study was designed to characterize transduction of non-human primate brain and spinal cord with a modified adeno-associated virus serotype 2, incapable of binding to the heparan sulfate proteoglycan receptor, referred to as AAV2-HBKO. AAV2-HBKO was infused into the thalamus, intracerebroventricularly or via a combination of both intracerebroventricular and thalamic delivery. Thalamic injection of this modified vector encoding GFP resulted in widespread CNS transduction that included neurons in deep cortical layers, deep cerebellar nuclei, several subcortical regions, and motor neuron transduction in the spinal cord indicative of robust bidirectional axonal transport.

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