A Neuren study of trofinetide, also known as NNZ-2566, for females with Rett Syndrome


Who are we?

Neuren Pharmaceuticals Limited is a biopharmaceutical company with global reach. We have a special commitment to areas of neuroscience where there are clear unmet medical needs. Our focus is the development of new therapies for brain injury, neurodevelopmental and neurodegenerative disorders. We have on-going clinical programs in traumatic brain injury, Rett syndrome and Fragile X syndrome. Learn more about us at our website:

What is trofinetide?

Insulin-like growth factor (IGF-1) is a protein in the human body that helps cells grow. In the brain, it contributes to the growth of brain cells and the connections between them (synapses) and plays an important role in repairing damaged cells. In the body, a small part of IGF-1 called glypromate or GPE separates from the main molecule. GPE is naturally present in the brain and acts on brain cells by itself in a different manner than the full IGF-1 molecule. Trofinetide (also known as NNZ-2566), is a modified version of GPE that readily crosses into the brain. Trofinetide is taken as a strawberry-flavored liquid. It is not yet FDA approved.  Clinical trials are underway to assess its safety and efficacy.

Why could trofinetide be helpful for Rett syndrome?

IGF-1 may be reduced in the brain in Rett syndrome and, as in other neurodevelopmental disorders, individuals with Rett syndrome may have problems with communication between brain cells. In particular, it has been observed that there are problems with the dendrites and their function in the synapse. In Rett syndrome, dendrites are sparse and immature. Trofinetide increases the length and branching of dendrites in a model of Rett syndrome.


In a model of Rett syndrome, increasing IGF-1 levels have been reported to correct deficits in dendrites and, in isolated cells from human Rett syndrome patients, both IGF-1 and GPE are able to partially reverse the deficits in cellular function.

What does the current trial of trofinetide involve?

The current study for individuals with Rett syndrome is a Phase 2 trial. This trial will include approximately 64 female participants between the ages of 5-15 years. 

The study primarily examines the safety profile in individuals with Rett syndrome. Trofinetide has already been studied in healthy human volunteers, as well as in individuals with Rett syndrome aged 16-45, and was shown to be generally safe and well tolerated.

This Phase 2 study is intended to confirm that trofinetide is a well-tolerated medicine that is worthy of further development for individuals with Rett syndrome. This study is also measuring efficacy (effectiveness). It includes measures looking at a number of areas of concern in Rett syndrome such as overall well-being, social communication and interaction, breathing, motor problems, behavior and seizures.

How does trofinetide work?

Trofinetide is very effective in improving the function of brain cells in animal models of developmental disorders such as Rett syndrome.  It is possible to explain this effect on brain function as follows:

In the brain, there are two important types of cells: 1) Neurons are the core type of brain cells that process information throughout the brain and nervous system via the connections between them. These connections are of two types: dendrites of the neuron receive information and the axon sends the message on to the next cell.  2) Glial cells are support cells that maintain and support the neurons. The glial cells are important for maintaining the function of dendrites and the connections between neurons (synapses), where communication and information processing takes place.

Microglia are a particular type of glial cell that maintain these connections. Microglia are also the brain’s immune cells which help regulate inflammatory responses when damage or infections arise.  Microglia also produce IGF-1 in the brain.

Trofinetide seems to work in two ways:

1) By controlling the activity of microglia:

  • Microglia work as immune cells to control infections or clear away damage in the brain.  When they do this, microglia release chemicals known as interleukins or cytokines. These chemicals can assist with response to infection, injury or damage, but they also can interfere with normal function of brain cells including maintenance of normal, healthy synapses.
  • Trofinetide can normalize the activity of microglia, reducing the release of cytokines, and restoring the capacity of microglia to maintain synapses.

2) Enhancing IGF-1 functions in the brain:

  • Animal models of Rett syndrome suggest that IGF-1 function may be reduced in the brain in developmental conditions such as Rett syndrome.  Because of this, communication between neurons may be disrupted and information processing by the brain may become impaired.
  • Trofinetide is believed to replace the function of GPE derived from IGF-1.  This may allow for some recovery of normal brain function.  Production of IGF-1 by microglia also may help to restore more normal levels of IGF-1 in the brain.

How do I register my interest in the Rett-002 Study?

Please view the Study Locations page on this site for a list of sites currently recruiting for this study. Some sites are currently preparing submissions to their individual Institutional Review Boards and can begin recruiting participants once this process is complete, which can take from weeks to months. As they receive approval to conduct the study, and can begin discussing enrollment, their contact details will be posted on the Study Locations page.  A contact form is also available so you can register your interest in participating in the study at a recruiting site.