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(Soft piano music)

2021. A man in his fifties is admitted to hospital in San Francisco, California, after experiencing a seizure.

He is disoriented, appears distracted and has difficulties with his speech.

An MRI scan reveals a lesion in the left temporal lobe of his brain.

The source of the lesion is unclear.

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(Sirens blaring)
- It was a mystery

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that consumed multiple
teams for multiple weeks,

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until our neurologist
and pathologist realized

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that on the section of his brain

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there were forms that looked like cysts,

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which is suspicious for amoeba.

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And that's how the diagnosis
was eventually made

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of Balamuthia mandrillaris,

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also known as the brain-eating amoeba.

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That's actually when I entered the story.

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(Light music)

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- Granulomatous amoebic encephalitis,

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or GAE, is caused when
the brain becomes infected

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by a free living amoeba called Balamuthia.

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It's one of the three pathogenic amoebae

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known to infect humans

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and cause a devastating brain infection.

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Fortunately, GAE is relatively rare.

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However, they have an
unusually high mortality rate.

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Balamuthia, for example,

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can infect someone when
soil is pushed up the nose

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or through the eye

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and from there the amoeba can
travel to the nervous system,

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primarily the brain.

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It literally begins to eat
its way through the tissue.

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- By the time I saw him,

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he'd actually been seen, given a diagnosis

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and he'd been started onto six medications

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which, until this year,
were standard of care,

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which includes two antifungals,

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two antiparasitics and two antibacterials.

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It's what has been used
successfully on a few survivors

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and it's also really toxic.

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So, multiple of these
drugs had had to be stopped

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following bone-marrow
suppression, kidney injury.

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We were losing drugs to treat him,

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and the lesions in his brain
were starting to enlarge,

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so I felt we were really
running quite short on options

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and that I had to think really hard

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if we were going to try to save his life.

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(Light music)

A previous case emerged as a crucial piece of the puzzle.

2015. A 74-year old woman was admitted to hospital in San Francisco with a cough and the loss of vision in her left eye.

Five days later, an MRI scan showed that her brain had become disrupted by numerous lesions.

The patient failed to respond to treatment, and died before a definitive diagnosis could be made.

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- We were trying to
figure out what killed her

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because no one knew.

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We used metagenomic
next-generation sequencing.

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This is a technique where we sequence

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all the RNA or DNA from a patient sample

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- in this case, cerebral spinal fluid.

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This eliminates the idea
that you have to know

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what you're looking for
before you look for it.

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In other words, you look for
everything simultaneously.

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We discovered that she had Balamuthia.

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(Light music)

2018. A screen by Joe DeRisi’s team of all medicines with US or EU regulatory approval revealed one drug that showed promise for treating Balamuthia infections.

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It's a drug called nitroxoline.

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It's been around for many, many years,

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mainly sold in Europe and in Asia

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as a drug to treat
urinary-tract infections,

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but it's never been used in
amoebic encephalitis before.

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This drug appears to
bind to divalent metals.

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In this way, its antibacterial activity

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is thought to happen

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because it's robbing
those organisms of metals

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that they need for their enzymes.

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So, we published that paper

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and, like many academics,

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maybe that was going to
be the end of the story.

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- When I saw that my
patient was getting worse,

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one of my colleagues advised me

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to look at Joe's paper and to talk to Joe.

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He picked up the phone and said,

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I know a company that makes it.

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(Soft piano music)

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(Speaking Mandarin)

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- Altogether, it took close to a month

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from request to shipping

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to getting it into UCSF pharmacy.

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It is not a trivial process,

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and I have to say that I
was really living on edge

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and in some state of terror
throughout that entire month.

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After a week, we got a repeat MRI

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that showed not only improvement

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but near resolution of these
huge areas of his brain

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that had been super
oedematous and swollen,

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and a huge abscess, and
it was getting better.

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We never stopped the other drugs

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but I do think that it was nitroxoline,

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especially given the in vitro data

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and the fact that he got
better when we added it.

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(Light music)

2022. The grandmother of a young Texan girl with an amoebic infection discovers a preprint article published on the 2021 case.

Physicians treating the child contact Asieris Pharmaceuticals for an emergency supply of nitroxoline.

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- It's kind of an amazing tale of science

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of how one thing leads to another

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and you don't really know
where it's going to go.

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We didn't know we'd
have fantastic partners

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in Asieris Pharmaceuticals.

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They were generous enough

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to gift us the drug to treat this patient.

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(Speaking Mandarin)

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- Right now, the CDC, on their website,

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is offering nitroxoline

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for patients with confirmed
Balamuthia, Acanthamoeba

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and or Naegleria.

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So, clinicians who have a patient

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who they think may have a
brain-eating-amoeba disease

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can call the CDC and ask
for a supply of nitroxoline.

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I think one of the really
cool things about this project

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is that everything comes together

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in a way that it kind of never does.

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The idea that I could
learn from my patient

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and from the original
patient who'd passed away

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and help a girl I've never
met... that feels amazing.

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I am so grateful to have gotten
to be a part of their story

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and that that little child is alive.

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(Light music)

Some patients in China have also recovered successfully from amoebic infections.

In 2024, Asieris Pharmaceuticals was granted permission to use nitroxoline in China as an Investigational New Drug to tackle amoebic infections.

Infections by Balamuthia and other amoebae are not just a public health issue in the US and China.

Global collaboration will help more people worldwide to recover from such infections.