PMD trial ties functional measures with NAD⁺ and redox biomarkers, offering a pragmatic view of mitochondrial modulation.
Primary mitochondrial disease (PMD) rarely attracts broad attention outside specialist circles, yet it sits uncomfortably close to the fault lines of modern geroscience. When mitochondria fail, energy falters, redox balance skews and physical function degrades in ways that look uncomfortably familiar to anyone studying aging. New results from OMEICOS Therapeutics’ PMD-OPTION study therefore resonate beyond the confines of rare disease, even as the company is careful to frame its work firmly within a defined clinical indication.
The Phase 2a PMD-OPTION trial evaluated OMT-28, an oral small-molecule modulator designed to influence mitochondrial metabolism and inflammatory signaling. The study used an open-label design with a 12-week untreated run-in period followed by up to 24 weeks of treatment, allowing each participant to serve as their own reference point. The primary endpoint focused on changes in growth differentiation factor 15 (GDF-15), a stress-associated biomarker often elevated in mitochondrial disorders, alongside a suite of functional and metabolic readouts.
Longevity.Technology: It is instructive to watch a rare mitochondrial disorder trial generate some of the clearest “healthspan” signals we ever see in humans; not because PMD is a stand-in for normal aging, but because it reduces the problem to its power supply and then asks a brutally practical question – can you move function, not just markers? OMEICOS is also a reminder that geroscience is settling into an engineering mindset: inflammation, redox balance and NAD⁺ metabolism are no longer treated as separate hobbies but as coupled systems that can, in principle, be modulated with a pill. The biomarker story, though, offers its own cautionary tale; when a primary endpoint fails to behave, it does not merely disappoint – it exposes how often our favored readouts are standing in for incomplete models of mechanism and meaning. If anything, that is the useful provocation here: as we push preventive longevity strategies from theory into policy and medicine, we will need endpoints that survive contact with messy human physiology, and trial designs that do not ask optimism to do the work of controls.
Functional measures over abstractions
The headline outcome was not the primary biomarker. GDF-15 did not decline in a way that supported its use as the central endpoint, a result the company attributes to OMT-28 acting downstream of stress-signal release rather than suppressing it directly. Instead, the more compelling signals emerged from functional assessments. Improvements were reported in the 12-Minute Walk Test and the 5x Sit-to-Stand Test, both pragmatic measures that regulators recognize and clinicians understand.
Approximately 60% of participants met the study’s responder criteria, a figure that invites interest and restraint in equal measure. Open-label designs can flatter signals, yet the presence of a structured run-in period provides context that pure before-and-after comparisons often lack. In a disease area with few therapeutic options, even modest functional gains carry weight.
NAD⁺, redox balance and the aging subtext
Where the trial begins to intersect with broader longevity discourse is in its metabolic readouts. Responders showed roughly 30% higher mean NAD⁺ levels, alongside improvements in the NAD⁺/NADH and GSH/GSSG ratios, moving closer to ranges observed in healthy controls. These ratios are not decorative details; they sit at the heart of mitochondrial electron transport, oxidative stress handling and cellular energy availability.
NAD⁺ has become a familiar character in aging research, sometimes unhelpfully so, drifting between serious biology and supplement marketing. In PMD, however, its relevance is difficult to dispute. Mitochondrial disorders represent an extreme phenotype of bioenergetic failure, and shifts in NAD⁺ availability and redox state offer a mechanistic bridge between molecular changes and physical capacity. Here, at least, the biomarkers align with function.
Dr Robert Fischer, CEO and CSO of OMEICOS, framed the results squarely in those terms. “Improving physical performance through enhanced mitochondrial metabolism and reduced oxidative stress holds great promise in PMD,” he said. The PMD-OPTION data, he added, “indicate a strong correlation between OMT-28 treatment, the observed positive impact on mitochondrial bioenergetics and fitness, and relevant clinical improvements in functional measures, which could translate into significant patient benefit.”
Fischer pointed in particular to “the profound effects on NAD⁺ and GSH levels, as well as simultaneous improvement of the NAD⁺/NADH and GSH/GSSG ratios” seen in responders, describing these as “integrative indicators of electron transport chain function improvements and cellular redox homeostasis.” Taken together, he argued, “the results offer a robust path for late-stage development.”
Safety, scale and the business signal
Across more than 220 individuals exposed to OMT-28 to date, the company reports an encouraging safety and tolerability profile. In rare disease development, that matters; mitochondrial patients are medically fragile, and safety liabilities can end programs abruptly. OMEICOS now positions OMT-28 as Phase 2b/3-ready later this year, with plans contingent on further development and partnering discussions.
For the longevity field watching from the sidelines, the lesson is less about extrapolation and more about discipline. PMD is not aging, but it clarifies what happens when energy metabolism collapses. Interventions that can restore even partial function in this setting strengthen the case that bioenergetic modulation is a legitimate therapeutic lever, not merely a biochemical curiosity.
When energy becomes policy
As populations age and health systems strain under chronic disease, the distinction between treating dysfunction and preventing decline grows thinner. Trials like PMD-OPTION do not answer that policy question, but they sharpen it. If mitochondrial performance can be moved in humans, measured in steps walked and chairs stood from, the argument for earlier, preventive engagement with bioenergetics becomes harder to ignore.
