Gene Therapy Extends Health Span in Aged Mice
A one-time gene therapy designed to increase production of the metabolic hormone FGF21 prolonged health span and preserved organ function in aged mice, according to a study from the Universitat Autònoma de Barcelona.
The work evaluated an adeno-associated viral vector therapy that drives expression and secretion of native fibroblast growth factor 21 from skeletal muscle. The treatment was given as a single intramuscular injection to old and geriatric male and female mice and followed over 27 months.
Treated animals showed a 20.54 percent increase in life expectancy, along with improvements across several measures associated with aging and age-related disease. The researchers report that the therapy normalized body weight and fat accumulation, improved insulin sensitivity and glucose homeostasis, and increased energy expenditure.
The treatment was associated with benefits across multiple organs. In adipose tissue, the researchers observed reduced adiposity and inflammation, as well as improved mitochondrial function. In the liver, the therapy helped preserve detoxification capacity and prevented age-associated changes including amyloidosis. Markers of renal damage were reversed in the kidney, while the heart showed reduced fibrosis and amyloidosis, with structure and function maintained.
The animals also retained physical performance, including coordination, strength, and muscular endurance. At the brain level, the researchers reported improved memory and learning, with performance described in the press release as comparable to that of young animals.
Transcriptomic and histological analyses suggested that the effects were linked to tissue-specific adaptations, including improved mitochondrial function, restored proteostasis through activation of protein synthesis, and increased hepatic detoxification capacity.
According to Fatima Bosch, who led the study, “these results position gene therapy based on FGF21 as a potentially translational strategy to promote healthy aging.” Source
Base Editing Human Embryos Avoids Some CRISPR Damage
Adenine base editing can introduce targeted genetic changes in early human embryos without some of the chromosomal abnormalities seen after conventional CRISPR-Cas9 cutting, according to a bioRxiv preprint.
The study compared the consequences of DNA double-strand breaks induced by CRISPR-Cas9 with the nicks and mismatches introduced by adenine base editors. The authors edited two loci, PCSK9 and HBG1/2, in human embryos and assessed editing efficiency, embryo development, large deletions, chromosomal integrity, and off-target activity.
The work suggests that base editing, which does not require a double-strand break, may avoid some of these genotoxic effects in early human embryos. But the findings do not remove the major scientific and ethical objections to heritable genome editing, including mosaicism, unintended edits, uncertainty over long-term consequences, and the fact that any resulting child could not consent to an intervention that may also affect future generations.
At the PCSK9 locus, adenine base editing was efficient and precise, with no bystander edits or indels detected around the target site in sequenced blastomeres. Editing at HBG1/2 was also efficient, although rare short insertions were detected. No large deletions were detected in samples from base-edited embryos. Chromosomal analysis also found that chromosomes 1 and 11, which contain the PCSK9 and HBG1/2 target sites, remained intact in every analyzed cell from base-edited embryos.
The delivery method appeared to matter. Embryos injected with adenine base editor mRNA at the two-pronuclear stage did not develop beyond early cleavage. In contrast, delivery of the base editor as a ribonucleoprotein was compatible with development to the morula and blastocyst stages.
Off-target activity remained a concern and varied by guide RNA. The HBG1/2 guide showed substantial off-target base editing at several candidate sites, including one site edited in about 37 percent of analyzed reads. The PCSK9 guide showed minimal off-target activity in the authors’ analyses, with one candidate site edited below 1 percent in embryo samples and no detectable editing at that site in the derived embryonic stem cell lines.
The authors also report mosaicism after editing at the one-cell stage, meaning not all cells in the same embryo carried the same edit. That remains a major barrier for any reproductive application, because a trophectoderm biopsy at the blastocyst stage may not accurately represent the cells that would form the fetus. Source
Immune Response May Shape CAR T Outcomes in Glioblastoma
The success of dual-target CAR T cell therapy in recurrent glioblastoma may depend partly on how a patient’s own immune system responds after treatment, according to a new study.
Researchers at the Perelman School of Medicine and Abramson Cancer Center at the University of Pennsylvania analyzed immune changes in cerebrospinal fluid and tumor samples from patients treated in a previously reported phase I trial of intracerebroventricular CAR T cell therapy. The earlier trial, found that the treatment could reduce tumor burden and extend survival in some patients with recurrent glioblastoma, but responses varied and relapse remained common. The new study sought to understand why some patients benefited more than others.
Using single-cell RNA sequencing, the researchers profiled 62 samples from 18 patients. They found that clinical outcomes were associated more strongly with changes in the endogenous immune compartment than with CAR T cell kinetics alone.
Patients who responded to therapy showed early expansion of cytotoxic natural killer cells in the cerebrospinal fluid. In contrast, non-responders had greater expansion of regulatory T cells, which can suppress immune responses, and higher baseline levels of immunosuppressive scavenger myeloid cells.
The findings suggest several possible strategies for improving future CAR T approaches in glioblastoma.
“We could prime the individual’s immune system with existing treatments that can deplete Tregs and immunosuppressive myeloid cells, or even ‘armor’ the CAR T cells with proteins that shuts down Tregs on their way to destroying tumor cells,” said co-senior author Zev Binder, assistant professor of neurosurgery. Source
uniQure Plans FDA Submission for Huntington’s Gene Therapy
uniQure plans to submit a Biologics License Application to the US Food and Drug Administration in the third quarter of 2026 for AMT-130, its investigational gene therapy for Huntington’s disease.
The company said the plan follows a recent Type B meeting with FDA, during which the agency communicated that a 3-year analysis from uniQure’s Phase I/II study could serve as the primary basis for a BLA seeking accelerated approval. FDA also wants to align with uniQure on the design of a required confirmatory study before submission, including the possible use of a concurrent control group receiving standard-of-care therapy rather than a sham procedure.
“Today's announcement reflects the outcome we have worked toward throughout our continued regulatory engagement with FDA, and we are deeply grateful for FDA’s genuine commitment to addressing the unmet need of Americans living with Huntington’s disease,” said Matt Kapusta, chief executive officer at uniQure, in the press release. “The FDA has agreed that our current clinical data can support a near-term BLA submission and has committed to work expeditiously with us to align on the design of the required confirmatory study.” Source
Houston Methodist Launches Cell and Gene Therapy Center
Houston Methodist has launched a new Center for Cell and Gene Therapy, with physician-scientist Malcolm Brenner appointed to lead the initiative.
The center will bring together scientists, clinicians, physician-scientists, and translational research staff across Houston Methodist’s research and clinical care settings. Its aim is to support the discovery and development of genetic and cellular therapies for congenital and acquired diseases, while accelerating the movement of preclinical findings into clinical evaluation.
“Malcolm Brenner is a pioneer in the field of cell and gene therapy and is uniquely qualified to lead Houston Methodist’s research efforts in this field,” said Jenny Chang, president and CEO of the Houston Methodist Academic Institute, in the announcement. “His vision and leadership will play a pivotal role in advancing our work in this space.”
Brenner is currently professor of pediatrics, medicine, molecular and human genetics, and translational biology at Baylor College of Medicine. He and his team will continue long-term collaborations with Baylor College of Medicine and Texas Children’s Hospital. Source
In Vivo CRISPR Therapy Succeeds in Phase 3 Trial
A single infusion of Intellia’s in vivo gene-editing therapy reduced monthly hereditary angioedema attacks by 87 percent. Read the article.
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