The post-2022 period revealed that genuinely novel non-amyloid mechanismsโTREM2 agonism, GLP-1 receptor stimulation, filamin A modulation, and progranulin/sortilin restorationโalso failed to produce clinical benefit at scale despite confirmed target engagement.
Archive for the ‘Neuroplasticity’ Category
๐๐ก๐ ๐ก๐ข๐ ๐ก๐๐ฌ๐ญ ๐๐ฅ๐ข๐ง๐ข๐๐๐ฅ ๐ญ๐ซ๐ข๐๐ฅ ๐๐๐ข๐ฅ๐ฎ๐ซ๐ ๐ซ๐๐ญ๐ ๐๐จ๐ซ ๐๐ง๐ฒ ๐๐ข๐ฌ๐๐๐ฌ๐ ๐ข๐ง ๐ฆ๐จ๐๐๐ซ๐ง ๐ฆ๐๐๐ข๐๐ข๐ง๐: ๐๐จ๐ฐ ๐๐จ๐ญ๐ก ๐๐ฆ๐ฒ๐ฅ๐จ๐ข๐- ๐๐ง๐ ๐ง๐จ๐ง-๐๐ฆ๐ฒ๐ฅ๐จ๐ข๐-๐ญ๐๐ซ๐ ๐๐ญ๐ข๐ง๐ ๐ญ๐ก๐๐ซ๐๐ฉ๐ข๐๐ฌ ๐๐๐ข๐ฅ๐๐ ๐ญ๐จ ๐๐ฅ๐ญ๐๐ซ ๐๐ข๐ฌ๐๐๐ฌ๐ ๐๐จ๐ฎ๐ซ๐ฌ๐ ๐ข๐ง ๐๐ฅ๐ณ๐ก๐๐ข๐ฆ๐๐ซ’๐ฌ ๐๐ข๐ฌ๐๐๐ฌ๐
Posted by Michael A. S. Guth on August 27th, 2026
AAV9 immunogenicity as a scalability trap. PROJECT OPTIMUS to boot.
Posted by Michael A. S. Guth on August 24th, 2026
AAV9 immunogenicity as a scalability trap. PROJECT OPTIMUS to boot. The anti-AAV9 titer cutoff of โค1:50 reflects a real immunological constraint: patients with prior AAV9 exposure mount a neutralizing immune response that reduces transduction efficiency and risks severe inflammation. https://www.sciencedirect.com/science/article/pii/S1359644626001571?dgcid=authorhttps://lnkd.in/g2YVjCDb Pre-existing anti-AAV9 antibodies are present in roughly 30โ50% of the general population, with the exact […]
Posted in Neuroplasticity, Pharma and Medical Device, Regulatory Medical Writing 
Comments Off on AAV9 immunogenicity as a scalability trap. PROJECT OPTIMUS to boot.๐๐๐ซ๐ ๐๐ญ๐ข๐ง๐ ๐๐๐-๐๐ ๐ข๐ง ๐๐๐: Causal Driver, Toxic Passenger, or Loss-of-Function Crisis?
Posted by Michael A. S. Guth on August 10th, 2026
https://authors.elsevier.com/a/1nYxN4r9Rkz1wZ TDP-43 is the most common neuropathological signature of ALS and one of the two most common pathologies in frontotemporal dementia (FTD), alongside fused in sarcoma (FUS) proteinopathy.10,11 Its cytoplasmic mislocalization and aggregation are observed in approximately 97% of all ALS cases, both sporadic and familial, with the notable exceptions of SOD1-linked disease and FUS-associated […]
Posted in Neuroplasticity, Pharma and Medical Device, Regulatory Medical Writing Comments Off on ๐๐๐ซ๐ ๐๐ญ๐ข๐ง๐ ๐๐๐-๐๐ ๐ข๐ง ๐๐๐: Causal Driver, Toxic Passenger, or Loss-of-Function Crisis?Google Scholar Publications Michael A. S. Guth
Posted by Michael A. S. Guth on August 9th, 2026
An Independent Review of Camrelizumab-Rivoceranib Combination Therapy for the Treatment of Hepatocellular Carcinoma and Rivoceranib for Gastric Cancer. Biomedical Journal of Sci & Tech Res, 58(2) (Aug 2024). https://biomedres.us/fulltexts/BJSTR.MS.ID.009118.php Surgical Implantation of Autologous Dopamine Neuron Progenitor Cells (DANPCs) Into the Putamen of Patients with Parkinsonโs Disease, Surgical Medicine Open Access Journal, (December 2024), Compounded Tirzepatide […]
Posted in About, AI Governance, Neuroplasticity, Regulatory Medical Writing Comments Off on Google Scholar Publications Michael A. S. Guth๐๐ก๐ ๐๐๐ ๐๐ซ๐ฎ๐ ๐ ๐ซ๐๐ฏ๐๐ฒ๐๐ซ๐ ๐ข๐ฌ ๐๐ซ๐จ๐ฐ๐๐๐
Posted by Michael A. S. Guth on August 5th, 2026
Since 1995, when the FDA approved riluzole for amyotrophic lateral sclerosis (ALS) โ offering a median survival extension measured in weeks โ more than 60 compounds have advanced to clinical evaluation, with the overwhelming majority failing to demonstrate efficacy.(p1) It is worth distinguishing, within that graveyard, between uninformative โfailedโ trials that lacked biomarkers and left […]
Posted in Featured, Neuroplasticity, Pharma and Medical Device, Regulatory Medical Writing Comments Off on ๐๐ก๐ ๐๐๐ ๐๐ซ๐ฎ๐ ๐ ๐ซ๐๐ฏ๐๐ฒ๐๐ซ๐ ๐ข๐ฌ ๐๐ซ๐จ๐ฐ๐๐๐Targeting TDP-43 in ALS: Regulatory Hurdles, Trial Design Deficiencies, and the Causal Evidence Gap for CTx1000
Posted by Michael A. S. Guth on July 29th, 2026
๐๐ฆ๐ฒ๐จ๐ญ๐ซ๐จ๐ฉ๐ก๐ข๐ ๐ฅ๐๐ญ๐๐ซ๐๐ฅ ๐ฌ๐๐ฅ๐๐ซ๐จ๐ฌ๐ข๐ฌ (๐๐๐) ๐ข๐ฌ ๐ ๐๐๐ญ๐๐ฅ ๐ง๐๐ฎ๐ซ๐จ๐๐๐ ๐๐ง๐๐ซ๐๐ญ๐ข๐ฏ๐ ๐๐ข๐ฌ๐๐๐ฌ๐. ๐๐๐๐ข๐๐ง ๐ฌ๐ฎ๐ซ๐ฏ๐ข๐ฏ๐๐ฅ ๐๐ซ๐จ๐ฆ ๐ฌ๐ฒ๐ฆ๐ฉ๐ญ๐จ๐ฆ ๐จ๐ง๐ฌ๐๐ญ ๐ข๐ฌ ๐๐ ๐ญ๐จ ๐๐ ๐ฆ๐จ๐ง๐ญ๐ก๐ฌ, ๐๐ง๐ ๐๐จ๐ซ ๐ฆ๐จ๐ฌ๐ญ ๐ฉ๐๐ญ๐ข๐๐ง๐ญ๐ฌ, ๐ง๐จ ๐๐ฏ๐๐ข๐ฅ๐๐๐ฅ๐ ๐ญ๐ก๐๐ซ๐๐ฉ๐ฒ ๐ฆ๐๐๐ง๐ข๐ง๐ ๐๐ฎ๐ฅ๐ฅ๐ฒ ๐ฌ๐ฅ๐จ๐ฐ๐ฌ ๐ญ๐ก๐๐ญ ๐๐๐๐ฅ๐ข๐ง๐. Since riluzole’s 1995 approval โ which extended median survival by only weeks โ more than 60 compounds have entered clinical trials for ALS, and nearly […]
Posted in Aging Adults, Neuroplasticity, Regulatory Medical Writing Comments Off on Targeting TDP-43 in ALS: Regulatory Hurdles, Trial Design Deficiencies, and the Causal Evidence Gap for CTx1000“๐๐ก๐ ๐ช๐ฎ๐๐ฌ๐ญ๐ข๐จ๐ง ๐ข๐ฌ ๐ง๐จ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฅ๐จ๐จ๐ค ๐๐ญ, ๐๐ฎ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฌ๐๐.” โ ๐๐๐ง๐ซ๐ฒ ๐๐๐ฏ๐ข๐ ๐๐ก๐จ๐ซ๐๐๐ฎ
Posted by Michael A. S. Guth on July 28th, 2026
“๐๐ก๐ ๐ช๐ฎ๐๐ฌ๐ญ๐ข๐จ๐ง ๐ข๐ฌ ๐ง๐จ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฅ๐จ๐จ๐ค ๐๐ญ, ๐๐ฎ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฌ๐๐.” โ ๐๐๐ง๐ซ๐ฒ ๐๐๐ฏ๐ข๐ ๐๐ก๐จ๐ซ๐๐๐ฎ For decades, Alzheimer’s research has looked at the same data: amyloid plaques, tau tangles, neuroinflammation. But what if we have been seeing it wrong? Two underappreciated forcesโchronic stress and an oral bacterium called P. gingivalisโmay be converging on the […]
Posted in Aging Adults, Neuroplasticity, Pharma and Medical Device Comments Off on “๐๐ก๐ ๐ช๐ฎ๐๐ฌ๐ญ๐ข๐จ๐ง ๐ข๐ฌ ๐ง๐จ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฅ๐จ๐จ๐ค ๐๐ญ, ๐๐ฎ๐ญ ๐ฐ๐ก๐๐ญ ๐ฒ๐จ๐ฎ ๐ฌ๐๐.” โ ๐๐๐ง๐ซ๐ฒ ๐๐๐ฏ๐ข๐ ๐๐ก๐จ๐ซ๐๐๐ฎ๐๐ก๐ ๐ข๐ง๐ญ๐ซ๐๐๐๐ฅ๐ฅ๐ฎ๐ฅ๐๐ซ ๐ฅ๐จ๐๐ค๐๐จ๐ฑ: ๐ก๐ฒ๐ฉ๐๐ซ๐ฉ๐ก๐จ๐ฌ๐ฉ๐ก๐จ๐ซ๐ฒ๐ฅ๐๐ญ๐๐ ๐ญ๐๐ฎ: ๐จ๐ง๐ ๐๐ฌ๐ฉ๐๐๐ญ ๐จ๐ ๐ญ๐ก๐ ๐๐ฎ๐๐ฅ ๐๐๐ช๐ฎ๐๐ฌ๐ญ๐ซ๐๐ญ๐ข๐จ๐ง ๐๐ฒ๐ฉ๐จ๐ญ๐ก๐๐ฌ๐ข๐ฌ ๐๐ฒ ๐๐ข๐๐ก๐๐๐ฅ ๐. ๐. ๐๐ฎ๐ญ๐ก
Posted by Michael A. S. Guth on July 27th, 2026
While Aฮฒ patrols the extracellular space, the microtubule-associated protein tau functions within neurons. In its normal state, tau stabilizes micro-tubules, which are crucial for axonal transport and structural integrity. Its pathological transformation into hyperphosphorylated, aggregated NFTs is another diagnostic hallmark of AD and strongly correlates with cognitive decline (Jellinger, 2020). The DSH suggests viewing pathological […]
Posted in Aging Adults, Neuroplasticity, Pharma and Medical Device, Regulatory Medical Writing Comments Off on ๐๐ก๐ ๐ข๐ง๐ญ๐ซ๐๐๐๐ฅ๐ฅ๐ฎ๐ฅ๐๐ซ ๐ฅ๐จ๐๐ค๐๐จ๐ฑ: ๐ก๐ฒ๐ฉ๐๐ซ๐ฉ๐ก๐จ๐ฌ๐ฉ๐ก๐จ๐ซ๐ฒ๐ฅ๐๐ญ๐๐ ๐ญ๐๐ฎ: ๐จ๐ง๐ ๐๐ฌ๐ฉ๐๐๐ญ ๐จ๐ ๐ญ๐ก๐ ๐๐ฎ๐๐ฅ ๐๐๐ช๐ฎ๐๐ฌ๐ญ๐ซ๐๐ญ๐ข๐จ๐ง ๐๐ฒ๐ฉ๐จ๐ญ๐ก๐๐ฌ๐ข๐ฌ ๐๐ฒ ๐๐ข๐๐ก๐๐๐ฅ ๐. ๐. ๐๐ฎ๐ญ๐กHas the definition of “positive neuroplasticity”ย and “negative neuroplasticity” evolved over time?
Posted by Michael A. S. Guth on July 23rd, 2026
Has the definition of “positive neuroplasticity”ย and “negative neuroplasticity” evolved over time? This publication,ย Vance DE, Roberson AJ, McGuinness TM, Fazeli PL. Howย neuroplasticity and cognitive reserve protect cognitive functioning. Jย Psychosoc Nurs Ment Health Serv. 2010 Apr;48(4):23-30. doi:ย 10.3928/02793695-20100302-01. PMID: 20349891,ย defined โPositive neuroplasticity refers to he physiologicalย ability of the brain to form and strengthen dendritic connections, produceย beneficial morphological changes, […]
Posted in Neuroplasticity, Pharma and Medical Device, Regulatory Medical Writing Comments Off on Has the definition of “positive neuroplasticity”ย and “negative neuroplasticity” evolved over time?๐๐ฎ๐๐ฅ ๐๐๐ช๐ฎ๐๐ฌ๐ญ๐ซ๐๐ญ๐ข๐จ๐ง ๐๐ฒ๐ฉ๐จ๐ญ๐ก๐๐ฌ๐ข๐ฌ ๐๐จ๐ซ ๐๐ฅ๐ณ๐ก๐๐ข๐ฆ๐๐ซ’๐ฌ ๐๐ข๐ฌ๐๐๐ฌ๐: ๐๐ก๐ ๐๐ฑ๐ญ๐ซ๐๐๐๐ฅ๐ฅ๐ฎ๐ฅ๐๐ซ ๐ฌ๐๐ซ๐๐จ๐ฉ๐ก๐๐ ๐ฎ๐ฌ: ๐๐ฆ๐ฒ๐ฅ๐จ๐ข๐-ฮฒย
Posted by Michael A. S. Guth on July 20th, 2026
๐๐ง ๐จ๐ฎ๐ซ ๐๐ฎ๐๐ฅ ๐๐๐ช๐ฎ๐๐ฌ๐ญ๐ซ๐๐ญ๐ข๐จ๐ง ๐๐ฒ๐ฉ๐จ๐ญ๐ก๐๐ฌ๐ข๐ฌ ๐๐จ๐ซ ๐๐ฅ๐ณ๐ก๐๐ข๐ฆ๐๐ซ’๐ฌ ๐๐ข๐ฌ๐๐๐ฌ๐: ๐๐ก๐ ๐๐ฑ๐ญ๐ซ๐๐๐๐ฅ๐ฅ๐ฎ๐ฅ๐๐ซ ๐ฌ๐๐ซ๐๐จ๐ฉ๐ก๐๐ ๐ฎ๐ฌ: ๐๐ฆ๐ฒ๐ฅ๐จ๐ข๐-ฮฒย We suggest reframing the Aฮฒ plaque not as a pathogenic endpoint but as an extracellular sarcophagusโa first-responder mechanism that sequesters insoluble or toxic material in the interstitial space. This view is supported by substantial evidence challenging Aฮฒ’s role as merely metabolic waste. From […]
Posted in Aging Adults, Neuroplasticity, Pharma and Medical Device Comments Off on ๐๐ฎ๐๐ฅ ๐๐๐ช๐ฎ๐๐ฌ๐ญ๐ซ๐๐ญ๐ข๐จ๐ง ๐๐ฒ๐ฉ๐จ๐ญ๐ก๐๐ฌ๐ข๐ฌ ๐๐จ๐ซ ๐๐ฅ๐ณ๐ก๐๐ข๐ฆ๐๐ซ’๐ฌ ๐๐ข๐ฌ๐๐๐ฌ๐: ๐๐ก๐ ๐๐ฑ๐ญ๐ซ๐๐๐๐ฅ๐ฅ๐ฎ๐ฅ๐๐ซ ๐ฌ๐๐ซ๐๐จ๐ฉ๐ก๐๐ ๐ฎ๐ฌ: ๐๐ฆ๐ฒ๐ฅ๐จ๐ข๐-ฮฒย