Science1 publisher2 min readPublished
A single-arm fasting pilot in Huntington's disease reports a 13% drop in a nerve-damage marker
Twenty people with early-stage Huntington's disease ate inside a six-to-eight-hour daily window for 12 weeks. They kept their weight and lean mass, and gained half a point on a severity scale that normally falls. The pilot had no control arm.
The Scientist · Science desk
What happened
- A 12-week pilot study, the first formal test of time-restricted eating in people with Huntington's disease, had early-stage patients confine all food to a six-to-eight-hour window each day.
- The 20 participants kept the schedule on average more than five days a week, reported few side effects, and held on to both body weight and lean muscle mass.
- Scores on the composite Unified Huntington's Disease Rating Scale improved by an average of 0.5 points over the three months of the intervention.
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Why it matters
- decision Funders now have to choose between treating an uncontrolled 20-person result as noise and paying for a randomized trial. The pilot hands them a measurable endpoint and a rough effect size to plan against.
- exposure A six-hour eating window needs no prescription, so patients and families can adopt it this week, in a disease where unintended weight loss is already a hazard.
- constraint The tolerability evidence covers early-stage patients who managed a daily app log, which is the easiest group to enrol and the least informative about whether the schedule is safe later in the disease.
- capability For a condition with no approved disease-slowing therapy, this puts a candidate intervention into testable form at close to zero manufacturing cost, with trial capacity as the limiting resource.
The 0.5-point figure gets its meaning from the comparison the authors supply. On the composite Unified Huntington's Disease Rating Scale, early-stage patients lose about one point a year [10]. Twelve weeks is a little under a quarter of a year, so the expected move across the study window was roughly 0.23 points down. Participants averaged half a point up, a gap of about 0.73 points [26]. That gap rests on 20 people with no comparison group [4][23].
Animal work had suggested intermittent fasting switches on cellular pathways that protect brain cells [21], but unintended weight loss is already a problem in Huntington's disease, so the researchers were unsure the schedule would be safe in people [22]. Participants picked their own window, usually late morning to early evening [4], and logged the day's first meal with a photo and a timestamp in a smartphone app [8]. On average they kept the schedule more than five days a week [6], which across 84 days is at least 60 days on plan [27]. Most settled in within the first week or two [7].
"When Russell first brought me the idea, I was skeptical," said Amie Hiller, professor of neurology at the OHSU School of Medicine [25]. "Weight loss is a major challenge for many people with Huntington's disease, so asking them to eat within a limited time window seemed counterintuitive" [16].
Neurofilament light, a protein released into blood when nerve cells are damaged, fell 13% on average [11]. In Huntington's disease it usually climbs as the disease advances [12]. "Neurofilament light typically rises as neurodegeneration continues, but after three months we observed a significant decrease," said Russell Wells, the OHSU medical student who led the work [24]. "For a pilot study, that was a remarkable finding" [14]. A single arm of 20 people over three months cannot separate that decrease from normal fluctuation in the marker or from the effects of being in a study. The authors say the result should not be read as proof that time-restricted eating slows the disease [23].
Several measures of mitochondrial activity improved, and they were made in participants' blood cells [13]. Blood cells are easy to sample. The disease kills neurons. "One theory is that fasting acts as a mild stressor that prompts cells to become more efficient," Wells said [18].
"These results suggest time-restricted eating deserves further study in a larger clinical trial," Wells said [15]. Such a trial is cheap to run against the alternative. The genetic cause of Huntington's disease has been known for decades, and no treatment has been approved that slows or stops it [19].
What to watch
- Whether a randomized, controlled trial gets registered and funded, and whether neurofilament light is set as its primary endpoint.
- Whether the schedule is tolerated by people with more advanced disease, where unintended weight loss is a bigger problem than in the early-stage group studied here.
- Whether another group reproduces a fall in neurofilament light over 12 weeks of time-restricted eating, in Huntington's disease or another neurodegenerative condition.