March 2024 update

In short

The update described how repeat dosing with FGF-1 is being studied over time. It also discussed open scientific questions about where FGF-1 travels in the brain after dosing.

The March update came just after the team returned from dosing its 22nd group of participants. Vika Montano was also managing repeat dosing for earlier participants who had reached six and 12 months since their first dose, to learn whether continued dosing makes a difference.

The update said some participants had reported further improvement at 9 and 15 months, which the team took as a sign that the added doses mattered. CEO Dan Montano was careful about what that meant. "Is that victory? No, not yet!" he wrote.

The team did not know whether people would decline again months or years later. It said it had to keep monitoring long-term effects, "both good and bad."

The puzzle of the "vanishing" FGF-1

Much of the update worked through a puzzle. A healthy person is thought to be born with about 500,000 dopamine-producing nerve cells. The number falls with age, and the symptoms of Parkinson's are believed to begin when it drops below about 200,000. Zhittya's hypothesis is that disrupted blood flow causes these cells to work poorly, go dormant and finally die.

When the Parkinson's project began in May 2022, the goal was to help the brain regain 100,000 to 200,000 working dopamine cells. In an earlier monkey study, done by researchers outside Zhittya, FGF-1 was injected directly into the brain. Zhittya chose a nasal spray instead.

Mr. Montano then set out the team's arithmetic. Earlier research suggested about 10,000 FGF-1 molecules must attach to a stressed cell to start a new cluster of blood vessels, and the team worked out that its goal would need about 200 million molecules in all. By its estimate, the first six-day nasal schedule delivered about 18 trillion molecules to the fluid around the brain, roughly 90,000 times that amount.

Yet the update said the first participants improved without recovering fully. They also reported changes nobody had aimed for: a returning sense of smell, less drooling, better sleep, clearer thinking and better memory.

The schedule had since reached Protocol 17, which the update said delivers about 36 trillion molecules over six months. The team believed daily dosing would not be better, because the receptors that capture FGF-1 need time to reset.

So where does the rest of the FGF-1 go? Mr. Montano suggested that some is flushed from the body and much may be used by billions of other brain cells, including those that handle smell, balance and memory. He wondered whether an older human brain has far more hidden damage, such as leaky vessels and tiny strokes, than a young monkey's. "We still have a lot to discover," he wrote.

Neuroplasticity

Dr. Jack Jacobs took up the same question. He wrote that FGF-1 is at work in the normal brain all the time, and that its levels are known to fall with age. His hypothesis was that the brains of older people with Parkinson's take up added FGF-1 well beyond the substantia nigra, the region where the dopamine cells sit. He noted that many participants had reported a brighter mood after dosing.

He then explained neuroplasticity, the brain's ability to form and reorganize connections between nerve cells in response to learning, new experience or injury. One example from published research was London taxi drivers, whose memory region grew as they learned the city's streets. He also cited a mouse study in which animals given FGF-1 after a stroke relearned a movement task.

Mr. Montano connected this to memory. A starved nerve cell pulls back the branches it uses to reach other cells. He asked whether restored blood flow might let those branches reach out again and bring a memory back, and answered: "We do not know!"

The update shared four comments from participants and family members, on balance, freezing, tremor, hand use, speech and facial expression. The rest covered an upcoming conference and other research areas.

This summary covers the Parkinson's research in the March 2024 update. The complete update, including the other topics it covered, is below.