For as long as there has been chemotherapy, there have been patients describing the same set of symptoms after treatment.

They can't follow conversations the way they used to.

They open a book and the words don't stick.

They search for words mid-sentence that used to be automatic.

They feel slower, foggier, less themselves — sometimes for months, sometimes for years.

For decades, the medical response to these reports was a shrug. Chemotherapy is hard. Cancer treatment is exhausting. Patients are stressed, sleep-deprived, depressed; of course their thinking feels off. Get some rest. Give it time.

The patients were right, and the medical response was wrong.

What patients were describing has a name: chemotherapy-induced cognitive impairment, or CICI. Colloquially, it's called chemobrain. And in the last fifteen years, the field has moved from dismissing it to characterizing it — to the point where the biological mechanism is now reasonably well understood and, more importantly, potentially addressable.

This piece walks through what's happening in the body, why it's been so easy to overlook, and where the science is heading.

How common is chemobrain?

The honest answer is that we don't know with precision — and that's part of the problem. Estimates in the literature range from about 15% to as high as 75% of patients on chemotherapy reporting cognitive symptoms during or after treatment.

The range is wide because the symptoms are heterogeneous, the measurement tools vary, and many patients underreport. But most researchers in the field agree on a floor: at least one in three patients on chemotherapy will experience clinically meaningful cognitive symptoms.

To anchor that:

  • The U.S. sees over 2 million new cancer diagnoses per year.
  • Roughly half of those patients receive chemotherapy.
  • One in three of those patients — at minimum — will experience CICI.

That is several hundred thousand new cases of chemobrain every year in the U.S. alone, on top of the millions of survivors already living with it.

There are no approved treatments.

What's actually happening: a neuroinflammatory cascade

For a long time, the leading explanation for chemobrain was that chemotherapy agents — particularly those known to cross the blood-brain barrier — were directly toxic to neurons. That story is part of the picture, but it doesn't explain everything. Many patients experience cognitive symptoms from chemotherapies that don't appear to cross the blood-brain barrier in any meaningful quantity.

The current best explanation is a process called neuroinflammation — and it shares striking similarities with what's now understood to happen in postoperative cognitive dysfunction (POCD).

Here's the simplified version of the cascade:

Step 1 — Systemic inflammation. Chemotherapy is a major physiological stressor. Cells are damaged. The immune system reacts. Signaling molecules called cytokines — TNF-α (tumor necrosis factor alpha), IL-1, IL-6, and others — surge into circulation to coordinate the response. This part is well understood and well documented.

Step 2 — The blood-brain barrier becomes permeable. Under sustained inflammatory pressure, the protective barrier that normally keeps the central nervous system insulated from peripheral inflammation becomes more permeable. Some cytokines cross. So, in some patients, do small molecules and immune cells that wouldn't normally reach the brain.

Step 3 — Microglial activation. Once in the brain, cytokines activate microglia — the brain's resident immune cells. Microglia are not bad actors; they exist to protect and maintain the brain environment. But chronically activated microglia release further inflammatory signals and shift from supporting nearby neurons to disrupting them.

Step 4 — Neuronal dysfunction. Disrupted neurons don't fire as cleanly. Synapses are weakened. The networks that handle memory, attention, and executive function take the first measurable hits. The symptoms patients describe — brain fog, word-finding difficulty, slower processing, lapses in working memory — are the downstream signature.

This cascade has been demonstrated in animal models. It is increasingly supported in human studies. And it is consistent with the clinical pattern: CICI is more common after longer or more aggressive treatment regimens, in patients with other inflammatory conditions, and in patients with baseline cognitive vulnerability.

Why it's been so hard to study

CICI sits at an inconvenient scientific intersection. It is partly an oncology problem, partly a neurology problem, partly an immunology problem, partly a psychiatric problem, and partly a quality-of-life problem. None of those fields has historically claimed it.

The measurement tools have been a separate challenge. Cognitive function is harder to standardize than tumor size or progression-free survival. Different studies use different test batteries, different timing, and different control conditions. The result is a body of literature that consistently shows the condition exists but is uneven in characterizing it.

There is also a more uncomfortable factor: when treatment-related side effects threaten the perception that a treatment is "working," they can be quietly deprioritized. For decades, the implicit clinical message to chemobrain patients was you have your life — be grateful. That was never an answer, and it is increasingly indefensible as the survivor population grows and lives longer.

The good news is that the science has caught up. The mechanism is no longer mysterious. What remains is the treatment.

What treatment might look like

If the neuroinflammatory cascade is the mechanism, the treatment goal is conceptually straightforward: interrupt the cascade.

The most promising approaches share a few characteristics:

  • They target inflammatory cytokines (TNF-α is the most studied target, but it is not the only one).
  • They cross the blood-brain barrier, so they can act at the site of the damage rather than only in the periphery.
  • They have well-characterized safety profiles — important in any population, and essential in patients already navigating cancer treatment.
  • They can be administered around the time of treatment, with the goal of preventing or limiting cognitive symptoms rather than treating them after they appear.

This is the design space Nulyn Science is working in.

Where Nulyn fits

Our lead asset, NS-001, is a small organic molecule that has been globally approved for an unrelated indication for many years. It has a long, well-documented safety record — including extensive data in elderly and medically complex patient populations.

What's new is what we've learned about its mechanism in the brain. NS-001 is a brain-penetrant inhibitor of the inflammatory cytokines implicated in CICI and POCD. In preclinical studies, a single preoperative dose limited microglial activation and preserved cognitive performance in animal models of both indications.

Because NS-001 is already approved, we are able to pursue the FDA's 505(b)(2) regulatory pathway — moving directly into Phase 2 trials in our target populations rather than starting from scratch.

We have submitted our pre-IND package to the FDA. Our first Phase 2 trial, in postoperative cognitive dysfunction, is scheduled to begin in the second half of 2026 in Brazil. A second Phase 2 in CICI is planned to follow.

A word to patients and survivors

If you've experienced any of what you've read here, you are not imagining it.

Chemobrain is real, common, and biologically grounded. Your symptoms are the consequence of a mechanism that — for the first time — researchers and developers are taking seriously, and that may be amenable to direct treatment within the next several years.

In the meantime: cognitive rehabilitation, exercise, sleep, and treatment of other inflammatory conditions all help some patients meaningfully. None of them are cures. All of them are foundations worth maintaining while better tools are being developed.

If you'd like to follow our work — or share your experience — you can reach us at hello@nulynscience.com.

The medical community owes its survivor population a real answer to chemobrain. We're working to provide one.