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

AUSTIN, Texas, Oct. 21, 2026 /PRNewswire/ -- Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage biotechnology company developing gene therapies designed to restore tumor-suppressor function in cancer and insulin-producing function in diabetes, today highlighted new peer-reviewed research in mice identifying an important role for the TUSC2 tumor suppressor gene in maintaining cellular processes associated with healthy brain aging and supporting broader understanding of how disruption of normal biological function may contribute to disease.

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.

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Contacts:

Genprex, Inc.
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SOURCE Genprex, Inc.