Genprex Highlights New Preclinical Data Identifying Role of TUSC2, the Gene Used in REQORSA®, in Maintaining Cellular Function During Brain Aging
The findings connect TUSC2 loss in mice with molecular changes also observed in human brain-aging datasets.
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Rhea-AI Summary
Genprex (NASDAQ: GNPX) highlighted peer-reviewed mouse research linking loss of TUSC2, the gene used in investigational REQORSA, to brain-aging changes.
The Meharry Medical College study, published in Mechanisms of Ageing and Development, found that TUSC2 loss disrupted mitochondrial function, protein quality control and neuronal communication pathways in the hippocampus, a brain region involved in learning and memory. Effects were more pronounced in males; females showed adaptive cellular stress responses. Analysis of existing human datasets found that TUSC2 expression declined significantly with age in 11 of 13 examined brain regions, with additional reductions in Alzheimer's disease datasets. Mouse findings overlapped with molecular changes in human hippocampal aging data. The study did not evaluate REQORSA as a treatment for aging or neurodegenerative disease; its development remains focused on cancer.
Positive
- Minor pointPeer-reviewed mouse research supports a role for REQORSA's therapeutic gene, TUSC2, in maintaining brain cellular function.
- Minor pointHuman dataset comparisons identified molecular overlap with mouse findings, supporting further investigation of TUSC2 in brain aging.
Negative
- Minor pointExploratory research did not evaluate REQORSA as a treatment for aging or neurodegenerative disease.
Details
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Key Figures
- Brain regions with age-related TUSC2 decline
- 11 of 13 brain regions
- Human gene-expression datasets
Key Terms
proteostasis medical
hippocampus medical
knockout medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
Collaborators publish new peer-reviewed study identifying sex-specific effects of TUSC2 loss on mitochondrial function, protein homeostasis, and synaptic pathways, alongside molecular similarities with human brain
Findings suggest that TUSC2 may play a foundational role in brain health
The study, entitled "Mitochondrial calcium sensor TUSC2 protects the aging hippocampus from proteostasis collapse in a sex-specific manner," was published in Mechanisms of Ageing and Development by researchers at Meharry Medical College. TUSC2 is the therapeutic gene used in Genprex's investigational REQORSA® gene therapy, which is being developed for the treatment of cancer.
The research found that loss of TUSC2 in mice was associated with substantial disruption of mitochondrial function, of protein homeostasis and of pathways involved in neuronal communication within the hippocampus, a region of the brain essential for learning and memory. These effects were markedly more pronounced in male mice than in females, suggesting important sex-specific differences in the biological response to TUSC2 deficiency.
Importantly, the researchers also analyzed existing human gene-expression datasets and found that TUSC2 expression declined significantly with age in 11 of 13 examined brain regions, with additional reductions observed in Alzheimer's disease datasets. Levels of TUSC2 protein in the hippocampus, as in the rest of the brain, decrease as humans age. Comparisons between the mouse findings and human hippocampal aging datasets identified overlapping molecular changes, supporting further investigation of TUSC2's role in brain aging.
While the research did not evaluate REQORSA as a treatment for aging or neurodegenerative disease, the findings expand scientific understanding of the biological functions of TUSC2, the gene underlying Genprex's lead oncology program.
"This research adds to our understanding of the diverse biological functions of TUSC2, the tumor suppressor gene at the center of our REQORSA oncology program," said Mark Berger, Chief Medical Officer of Genprex. "The findings highlight the important role TUSC2 plays in mitochondrial function, cellular stress responses, and protein homeostasis, while revealing intriguing differences between males and females. Importantly, the parallels identified between the preclinical findings and human brain aging data further reinforce the biological significance of TUSC2 beyond its established role in cancer. While these findings are exploratory, they contribute to a growing body of research into the broader functions of this important gene."
The research utilized an engineered mouse TUSC2 knockout (KO) model to investigate how the loss of TUSC2 accelerates molecular changes associated with hippocampal aging, before the onset of overt neurodegeneration. The findings establish the TUSC2 KO model as a valuable tool for investigating early stages of mitochondrial dysfunction, impaired protein homeostasis, and age-related changes in brain function.
Key study highlights:
- Sex-Specific Resilience: The study identified marked differences in mitochondrial stress resilience between male and female mice. While TUSC2 loss in males disrupted mitochondrial, protein homeostasis and synaptic pathways, females exhibited adaptive cellular stress responses, suggesting greater resilience to TUSC2 deficiency.
- Protein Homeostasis: TUSC2 deficiency was associated with impaired protein quality-control pathways and a significant increase in protein aggregate size in the male hippocampus, supporting a role for TUSC2 in maintaining cellular protein homeostasis.
- Synaptic Pathway Maintenance: The researchers identified substantial disruption of pathways involved in neuronal communication and synaptic function including differences between gene expression and corresponding protein levels, suggesting that TUSC2 contributes to the maintenance of normal synaptic processes.
These findings further support the importance of understanding how biological functions are disrupted in aging and how restoring TUSC2 may open new avenues for therapeutic intervention in age-related cognitive disorders.
About Genprex, Inc.
Genprex, Inc. is a clinical-stage gene therapy company focusing on developing innovative treatments designed to restore biological functions disrupted by disease. The Company's lead oncology program, REQORSA® Gene Therapy, is being developed for the treatment of lung cancer and is designed to deliver the TUSC2 tumor suppressor gene to help restore tumor-suppressive activity and address multiple pathways involved in cancer progression.
Genprex is also advancing an earlier stage gene therapy program for diabetes, designed to restore insulin-producing capability through the expression of key pancreatic transcription factors. Across its programs, Genprex is focused on translating innovative gene therapy approaches into meaningful therapeutic advances for patients with significant unmet medical needs.
For more information, please visit https://www.genprex.com/, register for our Email Alerts and follow us on LinkedIn, X, and Facebook.
Cautionary Language Concerning Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of management, are not guarantees of performance and are subject to significant risks and uncertainty. These forward-looking statements should, therefore, be considered in light of various important factors, including those set forth in Genprex's reports that it files from time to time with the Securities and Exchange Commission and which you should review, including those statements under "Item 1A – Risk Factors" in Genprex's Annual Report on Form 10-K for the year ended December 31, 2025.
Because forward-looking statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Genprex's ability to advance the clinical development, manufacturing and commercialization of its product candidates in accordance with projected timelines and specifications; the timing and success of Genprex's clinical trials, its intended regulatory submissions and any resulting regulatory approvals; the effect of Genprex's product candidates, alone and in combination with other therapies, on cancer and diabetes; Genprex's future growth and financial status, including Genprex's ability to maintain compliance with the continued listing requirements of The Nasdaq Capital Market and to continue as a going concern and to obtain capital to meet its long-term liquidity needs on acceptable terms, or at all; Genprex's commercial and strategic partnerships, including those with its third party vendors, suppliers and manufacturers and their ability to successfully perform and scale up the manufacture of its product candidates; Genprex's intellectual property and licenses; and Genprex's current expectations, estimates, forecasts and projections about the industry and markets in which it operates.
These forward-looking statements should not be relied upon as predictions of future events and Genprex cannot assure you that the events or circumstances discussed or reflected in these statements will be achieved or will occur. If such forward-looking statements prove to be inaccurate, the inaccuracy may be material. You should not regard these statements as a representation or warranty by Genprex or any other person that Genprex will achieve its objectives and plans in any specified timeframe, or at all. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Genprex disclaims any obligation to publicly update or release any revisions to these forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release or to reflect the occurrence of unanticipated events, except as required by law.
Contacts:
Genprex, Inc.
(877) 774-GNPX (4679)
GNPX Investor Relations Contact
Lisa DeScenza
ldescenza@lavoiegroup.com
GNPX Media Contact
Kalyn Dabbs
media@genprex.com
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SOURCE Genprex, Inc.
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did the TUSC2 brain-aging study highlighted by Genprex find?
Loss of TUSC2 in mice disrupted mitochondrial function, protein quality control and neuronal communication pathways in the hippocampus. The effects were more pronounced in males, while females exhibited adaptive cellular stress responses. Comparisons with human hippocampal aging datasets identified overlapping molecular changes.
Did Genprex's highlighted study test REQORSA for Alzheimer's disease or brain aging?
No. The research did not evaluate REQORSA as a treatment for aging or neurodegenerative disease. It examined TUSC2 loss in mice and analyzed existing human gene-expression datasets. REQORSA, which uses TUSC2 as its therapeutic gene, is being developed for cancer.
How did researchers study TUSC2 loss in the research highlighted by Genprex?
Researchers used an engineered TUSC2 knockout mouse model, in which the gene was disabled, to examine molecular changes associated with hippocampal aging before overt neurodegeneration. TUSC2 deficiency was associated with impaired protein quality-control pathways and a significant increase in protein aggregate size in the male hippocampus.