Research on Organoids Identifies Two Potential Rett Syndrome Treatments


As the medical field expands, so do the options for new and intriguing medical research. According to Drug Target Review, researchers from the University of California (UC) San Diego School of Medicine and Sanford Consortium for Regenerative Medicine recently sought to understand the underlying genetic cause of Rett syndrome using brain organoids. Initially, researchers used the organoids to replicate autism-spectrum disorder; at one point in time, Rett syndrome was thought to be part of this umbrella. Because Rett syndrome has since been found to have a distinct genetic element, researchers believed that organoids could help them uncover ways to address the root cause of this disorder. Read the full findings in EMBO Molecular Medicine.

Rett Syndrome

Altogether, many children with Rett syndrome have a MECP2 gene mutation. However, doctors are not yet sure how this gene impacts children or how it causes Rett syndrome; what they are sure of is that this mutation is usually spontaneous, rather than inherited. Rett syndrome is a rare neurological disorder that was once believed to be part of the autism spectrum. Typically, only females are affected; males with Rett syndrome usually do not live past birth. Patients are usually unable to live on their own. Normally, symptoms and characteristics appear between 1-1.5 years old. These include:

  • Flaccid muscles
  • Irritability
  • Loss of movement, coordination, and speech abilities
  • Slowed brain growth and a small head
  • Social anxiety
  • Uncoordinated breathing
  • Seizures
  • Failure to thrive
  • Constipation

Learn more about Rett syndrome here.

Brain Organoids

According to the Harvard Stem Cell Institute:

Organoids are tiny, self-organized three-dimensional tissue cultures that are derived from stem cells. Such cultures can be crafted to replicate much of the complexity of an organ, or to express selected aspects of it like producing only certain types of cells.

There are some complications associated with organoid use. For example, because the organoids are not actually connected to other bodily systems, and these particular organoids do not have a blood-brain barrier, brain organoids are not an exact match to the human brain. However, these unique structures do show promise for medical research. Beyond these limitations, organoids are also helpful in monitoring gene mutation responses, matching electrical impulse patterns, or observing genetic changes.

In this specific study, researchers sourced induced pluripotent stem cells (iPSCs) from patients with Rett syndrome and used these to create brain organoids. Additionally, they also engineered special organoids to model Rett syndrome to ensure the highest level of accuracy. Researchers determined that the structures without a MECP2 gene, or with a mutation, underwent changes in shape, neurotransmitter production, and gene expression, among others. Additionally, lowered calcium and electrical impulses altered brainwave function.

Drug Identification

Following organoid development, researchers used 14 therapies to treat the structures. Ultimately, two seemed effective: PHA 543613 and Nefiracetam, which have already been studied in a series of clinical trials. When treated with one or both of these drugs, the organoids saw higher calcium levels, neurotransmitter production, and electrical impulses. Now, researchers believe further research should be done in clinical trials on the impact of these two drugs on MECP2-related neurodevelopment conditions.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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