Use of skin, cheek cells may help monitor nomlabofusp effects in FA
Frataxin protein levels in animals closely tracked changes seen in heart, brain
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Treatment with nomlabofusp, Larimar Therapeutics’ experimental therapy for Friedreich’s ataxia (FA), leads to increased frataxin protein levels in cells throughout the body — changes that, according to new research, may be monitored using easily accessible skin or cheek cell samples.
The new findings, based on analyses in mouse, rat, and nonhuman primate models, showed that increases in frataxin protein levels in skin and cheek cells closely tracked changes seen in the heart and brain. These key organs are affected by the disease but are not feasible to biopsy in clinical practice, the team noted.
The research results support the use of skin samples “as a surrogate for the measurement of frataxin in tissues clinically relevant to Friedreich’s ataxia,” Larimar stated in a company press release announcing the study’s “cross-species findings.”
“We are pleased to publish these findings that further reinforce nomlabofusp’s mechanism of action and ability to restore [frataxin] levels in clinically-relevant tissues,” said Carole Ben-Maimon, MD, Larimar’s president and CEO. “Importantly, our studies show that after treatment, the increased levels in accessible tissues like skin and [cheek] cells reflect levels achieved in critical organs across mice, rats, and non-human primates.”
These new data support Larimar’s recently announced plans to seek accelerated approval of nomlabofusp by the U.S. Food and Drug Administration (FDA). Accelerated approval is a type of conditional approval that allows a therapy to be marketed based on early clinical data suggesting its likelihood of benefitting patients.
Larimar is specifically hoping the FDA will approve nomlabofusp based on data that the therapy boosts frataxin levels in skin cells. These newly published findings are intended to strengthen the case that changes seen in these accessible tissues reliably reflect effects in disease-relevant organs.
“The consistency seen across species further strengthens the translational relevance of our program, supports our planned accelerated approval pathway, and underpins our Biologics License Application (BLA) submission planned for June 2026,” Ben-Maimon said. “We are focused on … advancing nomlabofusp as the first potential disease-modifying therapy for patients with FA.”
The Larimar-funded study, “Nomlabofusp Treatment Produces Frataxin Levels That Correlate Across Peripheral Tissues: Preclinical and Clinical Support for Surrogate Tissue Sampling,” was published in the journal Clinical and Translational Science.
Cheek, skin cell samples are ‘reliable matrices’ for nomlabofusp
FA is a genetic disorder marked by abnormally low levels of frataxin, a protein that’s vital for the function of mitochondria, which are the so-called powerhouses of cells. Without frataxin, mitochondria don’t function properly, leading to issues with energy production. This especially affects nerve and muscle cells, which need significant amounts of energy to do their normal jobs.
Nomlabofusp is a subcutaneous, or under-the-skin, injection therapy designed to deliver a working version of the frataxin protein to the body’s cells, thus restoring mitochondrial function and slowing disease progression.
In theory, the therapy is only effective if it can deliver the protein to the most affected cells. However, it is not feasible to collect samples from affected tissues such as the brains and hearts of patients to determine whether it is working.
Early clinical studies have shown nomlabofusp can increase frataxin levels in patients’ skin cells, but whether these changes reflect what happens in less accessible organs has remained a key question.
To find out, four scientists at Larimar conducted a series of tests in animal models. Essentially, the researchers treated animals with nomlabofusb and then measured frataxin levels across multiple tissues, including skin, mouth, muscles, heart, and brain.
Across all species tested, increases in frataxin levels in skin cells were consistently associated with similar increases in disease-relevant tissues and organs.
“Accessible peripheral tissues — particularly skin and buccal epithelium [the cells that line the inside of the cheeks] — exhibited strong positive correlations in [frataxin] concentrations and can serve as practical, reliable matrices for quantifying [frataxin in FA] trials,” the researchers concluded. Per the team, “this strategy has the potential to accelerate translation of [frataxim] supplementation therapies, facilitate dose optimization, and improve clinical trial feasibility.”
