When mitochondria fail, these high-demand cells die first.
In a research center in Leiden, the Netherlands, a small British biotech has crossed the threshold from laboratory promise to human possibility. NRG Therapeutics has begun administering its experimental compound NRG5051 to healthy volunteers, testing whether repairing the cellular power plants of neurons can interrupt the slow devastation of ALS and Parkinson's disease. Both conditions have long resisted medicine's attempts to alter their course, and this trial represents one of the more grounded efforts yet to address not their symptoms, but their biological roots. The outcome, expected by year's end, will determine whether a new category of medicine—one that actually slows neurodegeneration—moves closer to becoming real.
- Millions of people living with ALS or Parkinson's have no treatment that slows their disease, only medicines that briefly soften its symptoms.
- NRG5051 targets the mitochondrial permeability transition pore—a cellular gateway whose improper opening causes neurons to collapse from the inside out.
- The trial's first doses have been administered to healthy volunteers in Leiden, marking the company's transformation from a research operation into a clinical-stage enterprise with something to prove.
- Backed by Novartis, the Michael J. Fox Foundation, and the British government, the company carries both scientific credibility and the weight of patient expectation into this Phase 1 work.
- If safety is confirmed by end of 2026, the path opens toward patient trials—and potentially the first drug ever shown to slow Parkinson's progression rather than merely mask it.
A biotech company based in Stevenage, England has taken its experimental drug NRG5051 into its first human trial, dosing healthy volunteers at a clinical research center in Leiden, the Netherlands. The compound is designed to address mitochondrial dysfunction—the breakdown of neurons' energy supply—which drives cell death in both ALS and Parkinson's disease. By blocking a cellular gateway called the mitochondrial permeability transition pore, NRG5051 has shown in laboratory models that it can protect neurons and reduce inflammation. The Phase 1 trial will test safety and tolerability in escalating doses, with results expected by the end of 2026.
The diseases in question represent some of medicine's most stubborn failures. ALS progresses rapidly and paralyzes its patients; the only recently approved drug targets a rare genetic subtype, leaving the majority of sporadic cases without meaningful treatment. Parkinson's is far more widespread and growing—projected to affect twice as many people by 2050—yet no existing drug slows its progression. Both conditions involve the accumulation of toxic proteins that overwhelm the very neurons that demand the most energy to function.
NRG's chief executive Neil Miller described the trial's start as a turning point, marking the company's entry into clinical-stage medicine. The company's backers include pharmaceutical venture arms from Novartis and M Ventures, disease-focused funders like the Michael J. Fox Foundation and Parkinson's UK, and British government innovation grants—a coalition that reflects confidence in both the science and the scale of the unmet need.
What the healthy volunteers in Leiden experience over the coming months will determine whether this idea advances toward patients. If NRG5051 proves safe, the company will move toward trials in people with ALS and Parkinson's. Success there could yield something medicine does not yet have: a treatment that actually alters the course of neurodegeneration rather than simply managing its symptoms.
A biotech company based in Stevenage, England has begun dosing the first human volunteers in a clinical trial of a drug designed to address a fundamental problem in two of the brain's cruelest diseases. NRG Therapeutics announced this week that participants have started receiving NRG5051, a compound engineered to fix broken mitochondria—the cellular power plants that neurons depend on to survive. The drug is being tested first in healthy people, with the goal of eventually treating patients with amyotrophic lateral sclerosis (ALS), also called motor neuron disease, and Parkinson's disease.
The science behind the approach is straightforward in principle, though the execution has taken years. Both ALS and Parkinson's involve the accumulation of toxic proteins—TDP-43 in ALS, alpha-synuclein in Parkinson's—that damage mitochondria and trigger a cascade of cellular death. The neurons most vulnerable are those that burn the most energy: the motor neurons that control movement in ALS patients, and the dopamine-producing neurons in the substantia nigra that fail in Parkinson's. When mitochondria fail, these high-demand cells die first. NRG5051 works by blocking the mitochondrial permeability transition pore, a gateway that, when opened inappropriately, allows the cell's power plants to collapse. In laboratory models of both diseases, blocking this pore has protected neurons and reduced inflammation.
The trial itself is being conducted at the Centre for Human Drug Research in Leiden, the Netherlands, with a design typical of early-stage drug testing. Healthy volunteers—not patients—are receiving escalating doses to establish that the drug is safe and that the body absorbs and processes it as expected. This Phase 1 work is meant to be completed by the end of 2026. If successful, it will inform the doses used when the company eventually moves to testing the drug in actual patients with ALS or Parkinson's.
The timing matters because both diseases represent enormous unmet medical needs. ALS is rare but devastating, progressing rapidly and leaving patients paralyzed. In 2023, the FDA approved a drug called Qalsody for a genetic form of ALS, but that treatment helps only a small fraction of patients—those with mutations in the SOD1 gene. The majority of ALS cases are sporadic, with no known genetic cause, and existing medicines offer little or no benefit. Parkinson's is far more common and growing. The disease affects millions worldwide, and projections suggest the number of people living with it will double by 2050 as populations age. Yet no drug currently available slows or stops the disease's progression; available treatments merely mask symptoms temporarily.
Neil Miller, NRG's co-founder and chief executive, framed the trial's start as a watershed moment for the company. The shift from preclinical research to human testing represents a fundamental change in what the company is—no longer purely a research operation, but a clinical-stage enterprise with skin in the game. Miller said the company's aim is to establish that blocking the mitochondrial permeability transition pore can actually slow or prevent disease progression, not just treat symptoms. That would be a genuinely new kind of medicine for both conditions.
The company itself is young and well-backed. It was founded by researchers who recognized the mitochondrial dysfunction problem and designed a solution around it. Investors include major pharmaceutical venture arms—Novartis, M Ventures—alongside disease-focused funders like the Michael J. Fox Foundation and Parkinson's UK. The British government has also supported the work through innovation grants. This mix of backing suggests confidence that the science is sound and that the market opportunity is real.
What happens next depends on what the healthy volunteers in Leiden experience over the coming months. If NRG5051 proves safe and well-tolerated, the company will move toward testing it in patients. If the drug works as hoped in those patient trials, it could become the first treatment capable of actually slowing Parkinson's progression—a category that does not yet exist. For ALS patients, it could offer hope beyond the narrow genetic forms currently treatable. Neither outcome is guaranteed. But the trial's start marks the moment when a laboratory idea becomes a testable claim about human biology.
Notable Quotes
Our ultimate objective is to establish the therapeutic efficacy of our novel mPTP inhibitors as disease-modifying medicines that are designed to slow or prevent the progression of neurodegenerative diseases.— Neil Miller, NRG Therapeutics co-founder and CEO
The Hearth Conversation Another angle on the story
Why does mitochondrial dysfunction matter so much in these two diseases specifically?
Because the neurons that die first in both ALS and Parkinson's are the ones that demand the most energy. Motor neurons in ALS are constantly firing to control movement. Dopamine neurons in Parkinson's are similarly high-load. When mitochondria fail, these cells starve before others do. It's not random which neurons die—it's the hardest-working ones.
So the drug isn't trying to cure the disease, just to keep the mitochondria working longer?
Exactly. It's not addressing the toxic proteins themselves. It's protecting the cell's ability to survive despite them. If you can keep the power on long enough, the neuron might not die. That's the bet.
Why test it in healthy people first if the goal is to treat sick people?
Because you need to know it won't poison anyone before you give it to patients who are already suffering. You need to understand how the body processes it, what doses are safe, what side effects might appear. You can't skip that step ethically or scientifically.
What makes this different from the ALS drug that was approved a few years ago?
Qalsody only works for people with a specific genetic mutation. Most ALS patients don't have that mutation. This drug, if it works, would work for anyone with ALS, regardless of genetics. Same with Parkinson's—there's no disease-modifying treatment at all right now, only symptom management.
How long until we know if this actually works in patients?
The Phase 1 trial finishes by end of 2026. Then they'll design and run Phase 2 trials in actual patients. That could take years. We're probably looking at 2028 or 2029 before anyone outside a clinical trial could potentially access it, assuming everything goes well.
What's the biggest risk at this point?
That it doesn't work. Or that it works in the lab but not in human brains. Or that it causes unexpected side effects that make it unsafe. Most drugs fail. This one has a real scientific foundation, but that doesn't guarantee success.