Riluzole trial is hopeful

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marty
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Riluzole trial is hopeful

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Riluzole is a medication that has been around quite a while and is generic. In this small trial there was a slowing in the progression of impaired brain glucose use, a primary focus of the study. There was also some sparing of cognitive decline compared to the placebo group.

Riluzole can be purchased with a prescription in Michigan for $36 per month with a GoodRx voucher, which is free. That is cheap compared to aducanumab! It's also generally well tolerated.

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https://doi.org/10.1093/brain/awab222

Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer’s disease

Dysregulation of glutamatergic neural circuits has been implicated in a cycle of toxicity, believed among the neurobiological underpinning of Alzheimer’s disease. Previously, we reported preclinical evidence that the glutamate modulator riluzole, which is FDA-approved for the treatment of amyotrophic lateral sclerosis, has potential benefits on cognition, structural and molecular markers of aging and Alzheimer’s disease. The objective of this study was to evaluate in a pilot clinical trial, using neuroimaging biomarkers, the potential efficacy and safety of riluzole in patients with Alzheimer’s disease as compared to placebo. A 6-month phase 2 double-blind, randomized, placebo-controlled study was conducted at two sites. Participants consisted of males and females, 50 to 95 years of age, with a clinical diagnosis of probable Alzheimer’s disease, and Mini-Mental State Examination between 19 and 27. Ninety-four participants were screened, fifty subjects that met inclusion criteria were randomly assigned to receive 50 mg riluzole (n = 26) or placebo (n = 24) twice a day. Twenty-two riluzole-treated and 20 placebo participants completed the study. Primary endpoints were baseline to 6 months changes in a) cerebral glucose metabolism as measured with fluorodeoxyglucose-positron emission tomography in pre-specified regions of interest (hippocampus, posterior cingulate, precuneus, lateral temporal, inferior parietal, frontal) and b) changes in posterior cingulate levels of the neuronal viability marker N-acetylaspartate as measured with in vivo proton magnetic resonance spectroscopy. Secondary outcome measures were neuropsychological testing for correlation with neuroimaging biomarkers and in vivo measures of glutamate in posterior cingulate measured with magnetic resonance spectroscopy as a potential marker of target engagement. Measures of cerebral glucose metabolism, a well-established Alzheimer’s disease biomarker and predictor of disease progression, declined significantly less in several pre-specified regions of interest with the most robust effect in posterior cingulate, and effects in precuneus, lateral temporal, right hippocampus and frontal cortex in riluzole-treated subjects in comparison to placebo group. No group effect was found in measures of N-acetylaspartate levels. A positive correlation was observed between cognitive measures and regional cerebral glucose metabolism. A group by visit interaction was observed in glutamate levels in posterior cingulate, potentially suggesting engagement of glutamatergic system by riluzole. In vivo glutamate levels positively correlated with cognitive performance. These findings support our main primary hypothesis that cerebral glucose metabolism would be better preserved in the riluzole treated group than in the placebo group and investigations in future larger and longer studies to test riluzole as a potential novel therapeutic intervention for Alzheimer’s disease.
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floramaria
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Re: Riluzole trial is hopeful

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marty wrote:Riluzole is a medication that has been around quite a while and is generic. In this small trial there was a slowing in the progression of impaired brain glucose use, a primary focus of the study. There was also some sparing of cognitive decline compared to the placebo group.

Riluzole can be purchased with a prescription in Michigan for $36 per month with a GoodRx voucher, which is free. That is cheap compared to aducanumab! It's also generally well tolerated.

................................................................

https://doi.org/10.1093/brain/awab222

Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer’s disease
.
Hi Marty, Interesting! I tried to open the article but I do not have access. I was curious about exactly how it modulates glutamate since that is a nonspecific term and found an article on PubMed.
Among other things, the article says this about riluzole: “These effects are mediated by blockade of glutamate transmission, stabilizing of sodium channels and blockade of gamma-aminobutyric acid (GABA) reuptake.
https://pubmed.ncbi.nlm.nih.gov/9750003
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marty
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Re: Riluzole trial is hopeful

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The mechanism of action is unclear. Initially it was thought to block glutamate release. Glutamate is an excitatory neurotransmitter and is plentiful in the brain. Excessive glutamate stimulation is thought to account for some of the toxicity of hypoxemia in the immediate aftermath of reoxygenation. Glutamate stimulation is thought to accelerate the degeneration seen in ALS. Riluzole is known to have modest benefit in that disorder.

It less clear as to how Riluzole works in the central nervous system. It does reduce the effect of glutamate but how that happens may be secondary to decreased release of glutamate by direct or indirect means. Speculation.

Here is a reference. https://www.tandfonline.com/doi/full/10 ... 20.1771734
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floramaria
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Re: Riluzole trial is hopeful

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marty wrote: It less clear as to how Riluzole works in the central nervous system. It does reduce the effect of glutamate but how that happens may be secondary to decreased release of glutamate by direct or indirect means. Speculation.

Here is a reference. https://www.tandfonline.com/doi/full/10 ... 20.1771734
Thanks! I'll have a look.
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