Genervon Biopharmaceuticals presented its latest research data at the American Society for Experimental Neurotherapeutics 2023 Annual Meeting

PASADENA, CA, USA March 14, 2023 – Genervon Biopharmaceuticals presents its latest research data at the American Society for Experiment Neurotherapeutics 2023 Annual Meeting in Bethesda, MD from March 13 to March 15, 2023.

ALS is a devastating disease without any disease-modifying drugs available. In recent years a lot of research has shown that the protein TDP-43 is present in the postmortem tissue of 97% of ALS patients. TDP-43 is also elevated in ALS patients. Genervon recently studied how GM6 impacts TDP-43 levels in human TDP-43 transgenic mice (TAR4), as therapeutic for ALS and frontotemporal lobar degeneration (FLTD). The data are presented at ASENT 2023.

GM6 is a derivative of motoneuronotrophic factor (MNTF) which functions as a regulator of key biomarkers. GM6 has been shown to be safe and tolerable in four clinical trials. The Phase 2A ALS clinical trial showed favorable shifts in blood biomarkers of tau, TDP-43, and SOD1 as well as positive signals of clinical outcomes. The mean change in slope for plasma TDP-43 from baseline to week 12 in the GM6-treated groups was -3.513 pg/ml, which represents a decrease of 34%, while the mean change in slope was 0.493 pg/ml in the placebo group, which represents an increase of 6% from baseline (p=0.0078 95% CI). This significant difference observed between the GM6-treated and placebo ALS patients suggests that GM6 could be beneficial to slow down the ALS disease progression through modulating TDP-43.

Human TDP-43 transgenic mice (TAR4-PrP) recapitulated features of ALS, TDP-43 cleavage, phosphorylation, and aggregation, gait disturbances, and early lethality.  Genervon recently studied the impact of GM6 on TDP-43 levels in TAR4-PrP mice. TAR4-PrP mice were treated with GM6 at 1 mg/kg, 10 mg/kg, or saline subQ dosing (daily) starting at 10 months of age until they started to show behavioral changes. In TAR4-PrP mice, human TDP-43 (hTDP-43) is expressed in the brain and spinal cord, regions relevant to TDP-43 proteinopathies, and GM6 causes a dose-dependent downregulation of hTDP-43. Treatment with GM6 at 10 mg/kg/day resulted in a 40% reduction in hTDP-43 in the brain. It also attenuated brain (+20%) and body (+25%) weight loss. Immunoreactive staining of hTDP-43 in the spinal cords at the end of the study was reduced by almost 300%.

Treatment with GM6 in TAR4-PrP mice also demonstrated an improvement in behavioral changes. The time to abnormal hind reflex onset was significantly extended from 52 weeks to 120 weeks.  It is noted that similar benefits of GM6 were observed in previous studies with  SOD1 tg mice where maintenance of motor neurons in the 5 mg/kg GM6 treated mice was 200% higher compared to control animals.  Also, a reduction in hSOD1 protein levels was seen (>50%) in the GM6-treated mice.

GM6 may be a feasible approach in the treatment of ALS and FTLD as a pleiotropic regulator which simultaneously acts upon multiple extracellular receptors to modulate a series of signaling pathways mediating inflammation, decreased TDP-43, SOD1, and tau toxicity and increased pro-survival responses.

Genervon Biopharmaceuticals presented its latest research data at the American Society for Experimental Neurotherapeutics 2022 Annual Meeting

PASADENA, CA, USA, March 2, 2022 – Genervon Biopharmaceuticals presented its latest research data at the American Society for Experimental Neurotherapeutics 2022 Annual Meeting in Bethesda, MD from February 27 to March 3, 2022. New Data has shown that GM6 attenuates activated cofilin and β-arrestin2 impact on pathological tau and decreasing tau aggregates in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). A video presentation is available at https://youtu.be/hezKnI9uMGk.

Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are major causes of dementia in the elderly. Recent studies have implicated both activated cofilin and β-arrestin2 in the pathogenesis of AD and FTLD. The deposition of amyloid β (Aβ) peptide into amyloid fibrils and hyperphosphorylated tau into neurofibrillary tangles (NFTs) are key processes in the pathogenesis of the diseases. Recent studies have shown that activated cofilin and β-arrestin2 are increased in the brains of patients with AD and FTLD, associating them in the disease process. In addition, studies have shown that reduction in cofilin and β-arrestin2 in vitro and in vivo reduces the impact on AD and FTLD.

Previously, GM6 has shown effects in lowering amyloid in an APP mice model, lowering tau in tau mice, and reducing inflammation. In the 2022 presentation, when GM6 was treated at the beginning of p-tau formation, tau levels were reduced, p-tau was lessened, and inflammation was moderated. In both transgenic mice, behavioral changes were attenuated in the GM6 treated mice. In addition, in both the APP and tau mice, cofilin and β-arrestin2 levels decreased by ~80% in the brains, and amyloid plaques decreased by 60% and p-tau was reduced by 70%. In both the APP and h-tau mice, inflammation cytokines TNF-α, IL-1 β, IL-6, and TGF-β were significantly reduced (~80-90%). The data suggest that GM6 has a significant impact on AD and tauopathies partly by mediating changes in cofilin and β-arrestin2. In conclusion, these findings suggest that GM6 may be a feasible approach to attenuate AD and FTLD pathology as a combination therapy by concurrently reducing inflammation, activated cofilin, β-arrestin2, Aβ, and hyperphosphorylated tau.

Genervon Biopharmaceuticals identified and developed the innovative first-in-class hexapeptide, GM6, an active 6-amino acid fragment of Motoneuronotrophic Factor (MNTF) which is detected in the human placenta with its highest expression at the 9th week of gestation. GM6 penetrates the blood-brain barrier and was shown to have neuroprotective and disease modifying effects in models including Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD), Multiple Sclerosis (MS), Spinal cord injury (SCI) and stroke. GM6 was shown to be safe and tolerable in a Phase 1 clinical trial in healthy subjects, in an ALS Phase 2A clinical trial, and in a Phase 2A PD clinical trial. GM6 also showed positive signals in clinical observations and favorable shifts in biomarkers in the Phase 2A ALS trial. Genervon has a rich clinical pipeline: GM6 is Phase 3 ready for ALS, Phase 2b ready for PD, Phase 2 ready for AD, MS, SCI, and Stroke recovery.

Genervon to Present GM6’s Effect in Modulating Alzheimer’s Disease at the ASENT 2021 Annual Meeting

PASADENA, CA, USA, February 22, 2021 -- The American Society for Experimental Neurotherapeutics invited Genervon Biopharmaceuticals to present its latest research data at the ASENT 2021 Annual Meeting in Bethesda, MD from February 22-25. Genervon will be giving a presentation on GM6’s new data on attenuating inflammation in Alzheimer’s disease pathology via modulation of fibrinogen by reducing Aβ and tau.  The slide presentation is available at http://www.genervon.com/s/GM6-attenuates-inflammation-in-Alzheimers.

Alzheimer's disease (AD) clinical trials focused on a single-target anti-amyloid strategy have been unsuccessful to date. Currently the pipeline of AD drugs under development target multiple mechanisms, but each drug only aims to modify one mechanism such as reducing amyloid, reducing tau, lowering inflammation, reducing vasculature involvement, increasing neuroprotection or metabolism bioenergetics, etc. The AD research community is suggesting that the answer to treating AD will lie in using multiple single-target drugs in combination, or drugs with multiple effects in one molecule, because AD is an enormously complex disease with multiple causes and pathologies. Genervon proposes that GM6 is such a pleiotropic molecule with concurrent effects on the complex pathologies.

GM6 has previously shown effects in lowering amyloid in an APP mice model, lowering tau in tau mice, and reducing inflammation. In the 2021 ASENT presentation, GM6 was shown to also attenuates inflammation in AD pathology via modulation of fibrinogen, the vasculature involvement in AD. In the APP mice, fibrinogen levels decreased by 75% in the brains, amyloid plaques decreased by 60%, and Nerve Growth Factor (NGF) increased by 600%.In both APP and h-tau mice, inflammation cytokines TNF-α, IL-1β, IL-6, and TGF-βwere reduced by 80-90%. GM6 may be a feasible approach in the treatment of AD as a pleiotropic regulator which simultaneously acts upon multiple extracellular receptors to modulate a series of signaling pathways mediating inflammation, decreased Aβtoxicity, and pro-survival responses. (Click on the video above for the presentation)

Genervon Biopharmaceuticals identified and developed the innovative first-in-class hexapeptide, GM6, an active 6 amino acid fragment of Motoneuronotrophic Factor (MNTF) which is detected in the human placenta with its highest expression at the 9th week of gestation. GM6 penetrates the blood-brain barrier and was shown to have neuroprotective and disease modifying effects in models including Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD), Multiple Sclerosis (MS), Spinal cord injury (SCI) and stroke. GM6 was shown to be safe and tolerable in a Phase 1 clinical trial in healthy subjects, in an ALS Phase 2A clinical trial, and in a Phase 2A PD clinical trial. GM6 also showed positive signals in clinical observations and favorable shifts in biomarkers in the Phase 2A ALS trial. Genervon has a rich clinical pipeline: GM6 is Phase 3 ready for ALS, Phase 2b ready for PD, Phase 2 ready for AD, MS, SCI and Stroke recovery.

Genervon to present at the American Society for Experimental Neurotherapeutics (ASENT) 2019 Global Healthcare Conference

March 3, 2019

Genervon Biopharmaceuticals is scheduled to present again this year at the ASENT 2019 Annual Meeting and Global Healthcare Conference on Neurotherapeutics in Maryland on March 28. Genervon will be presenting its published papers…

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GM6 Attenuates Alzheimer's Disease Pathology in APP Mice

March 2, 2019

“GM6 Attenuates Alzheimer's Disease Pathology in APP Mice” has been published online by Molecular Neurobiology on 2/23/2019 (PMID number 30798443). The paper concludes, “Application of GM6…

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GENERVON PRESENTED ITS GM604 MECHANISMS OF ACTION AT THE 29TH INTERNATIONAL SYMPOSIUM ON ALS/MND IN GLASGOW, UK

March 1, 2019

Genervon Biopharmaceuticals presented its GM604 Mechanisms of Action at the 29th International Symposium on ALS/MND held on Dec. 8-9, 2018 in Glasgow, UK. The paper was published in Translational Neurodegeneration at the same time. The full published paper text can be found…. 

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