Genetics and stem cells

Misleading claims of 'cure for Down's syndrome'

The Mail Online suggests there could be a “cure” for Down’s syndrome, saying that scientists have “discovered a way to reverse the learning difficulties caused by the condition”.

It is not apparent from this headline that the research in question was carried out in mice, not people with Down’s syndrome. The mice had a genetic abnormality that mimics some of the characteristics of Down’s syndrome in humans. The study investigated the effects of a compound (called Sonic hedgehog pathway agonist, SAG) which the researchers thought might reduce some of the aspects of problems with the brain structure, learning and memory of mice.

When the mice were given SAG at birth, by adulthood they had more normal development in the part of the brain involved with balance and coordination than untreated mice. The treated mice also showed improvements in nerve signalling in a part of the brain involved with memory and spatial awareness. They also performed better on a test of learning and memory. However, SAG treated mice still showed differences in some nerve cell signalling and behavioural tasks compared to normal mice.

It is not possible to correct the underlying genetic abnormality that causes Down’s syndrome, so talk of a “cure” is misleading.

The current findings are encouraging, and are likely to be followed up by more animal research. This may help scientists better understand Down’s syndrome and to develop new therapies for people with the condition. However, it is far too early to say with certainty whether this will be successful.

Where did the story come from?

The study was carried out by researchers from Johns Hopkins University, Baltimore, and the Institute on Alcohol Abuse and Alcoholism, Rockville, both in the US, and Jeju National University School of Medicine, South Korea. Funding was provided by the Down Syndrome Research and Treatment Foundation, and other US research organisations.

The study was published in the peer-reviewed scientific journal, Science Translational Medicine.

In the research paper and an accompanying editorial, the authors are suitably cautious in their predictions about the potential for future treatments. However, this caution is abandoned in the Mail Online’s headline “A 'cure' for Down's syndrome? Scientists discover compound that reverses learning difficulties caused by the condition”. The headline gives no indication that:

  • the research was carried out in mice
  • it did not aim to reverse the condition’s underlying genetic defect (to “cure” the condition) 
  • the treatment did not remove all the effects of the disorder

While this research may eventually lead to new treatments to alleviate some aspects of Down’s syndrome, this is likely to be a long way off and is not guaranteed. Therefore, the headline may offer false hope to individuals and families affected by Down’s syndrome.

The headline also implies that the research suggests the condition could be cured. This is not the case. Subheadings later in the article do make it clear that the research has been conducted in mice and that the compound tested is not approved for use in humans.

What kind of research was this?

This animal research involved a mouse “model” of Down’s syndrome. The researchers tested an experimental drug to see whether it could improve the mice’s performance in cognitive tasks involving learning and memory.

Down’s syndrome is one of the most common chromosomal abnormalities; it is caused by having an extra copy of part or all of chromosome 21. The condition has characteristic physical features and a variety of associated health risks, including heart problems. Another common feature is that most people with Down’s have some degree of developmental, intellectual and learning impairment, including problems with movement, language and communication.

The researchers speculate that while the underlying genetic abnormality cannot be corrected, some of the “abnormalities in brain structure resulting from the chromosomal change may not be so [unchangeable]”. For example, the part of the brain involved in balance and coordination called the cerebellum is smaller and has fewer cells in people with Down’s syndrome. This is thought to be because in people with Down’s syndrome, the precursors to these cerebellum cells do not respond properly to a protein (“Sonic hedgehog”), which would normally encourage them to divide and generate new cells during brain development.

Another part of the brain which is involved in learning and memory, the hippocampus, is also affected by Down’s syndrome. The researchers wanted to test whether giving the mice a chemical which mimics the effects of Sonic hedgehog shortly after birth would improve the cerebellum problems, and what effect this would have on the mice’s learning and memory.

Animal studies are very useful for understanding the biological processes underlying disease, and testing potential new treatments, as these early studies could not be carried out in humans and there are many similarities to human biology. However, there are also differences, and it is a big jump to apply the findings of this study involving an animal model directly to people with a condition with complex effects such as Down’s syndrome.

What did the research involve?

This research used “Ts65Dn mice”, which are mice with a genetic abnormality similar to that seen in humans with Down’s syndrome. These mice are said to share some similar features with human Down’s, including learning and functional problems and having a smaller cerebellum with reduced number of cells.

The research involved injecting newborn Ts65Dn mice with a single dose of a compound called “Sonic hedgehog pathway agonist” (SAG). This had previously been shown to promote cellular growth in the cerebellum and promote normal structure in young mice. But the effects in adult mice had not been assessed. The researchers looked at what effects this compound had on the cerebellum of mice when they reached adulthood (16 weeks). They also compared nerve cell signalling in the cerebellum and hippocampus in SAG treated and untreated Ts65Dn mice and normal mice.

The treated and untreated Ts65Dn mice and normal mice were assessed using various behavioural tests including the Morris water maze test. This tests spatial learning and memory, which involve the hippocampus.

What were the basic results?

When newborn Ts65Dn mice were given an injection of SAG at birth, their cerebellum structure developed more normally, and when they became adults they had the same cross-sectional area and number of cells as mice without the genetic abnormality. SAG also made some aspects of communication between nerve cells in the cerebellum and hippocampus more normal, but not all.

In the water maze, untreated Ts65Dn mice performed worse than mice without the genetic abnormality, but SAG treated Ts65Dn mice performed similarly to the normal mice. SAG treatment did not improve performance of the Ts65Dn mice on other tasks not related to the hippocampus.

How did the researchers interpret the results?

The researchers conclude that their results confirmed an important role for Sonic hedgehog signalling in development of the cerebellum. They suggest that it may play a role in hippocampus function in a Down’s syndrome mouse model. They say that the results suggest a possible direction for developing treatments to improve cognitive function in people with Down’s syndrome.

An accompanying editor’s summary says, “The findings of this paper do not imply an imminent cure for Down syndrome or a treatment for humans in the near future. The effects of Sonic hedgehog on brain development in humans are not yet fully understood, and overactivation of this pathway has been linked to some diseases. Nevertheless, this study provides insights into the biology of Down syndrome and its molecular underpinnings, which may eventually lead to improved therapies for [people with Down’s].”


This is interesting research investigating the effects on brain structure, learning and memory of using a chemical to treat mice with a condition similar to Down’s syndrome.

The research found some positive results including normalisation of the structure of the cerebellum and improvements in learning and memory in the water maze test. However, it is far too early to say whether a similar treatment could be developed for use in humans, and what its effects might be.

The chemical used mimics the effect of the Sonic hedgehog protein, which is naturally found in our bodies. This protein is essential for a wide range of developmental processes in the body. Any treatments related to this protein would need to be closely studied to make sure that they did not interfere with any of these vital processes.

In an accompanying press release one of the study authors, Professor Roger Reeves of Johns Hopkins University, adds due caution about the unknown safety of the compound in humans, and the possibility for serious side effects. He says, “The problem is that altering an important biological chain of events like sonic hedgehog would likely have many unintended effects throughout the body, such as raising the risk of cancer by triggering inappropriate growth. But now that the team has seen the potential of this strategy, they will look for more targeted ways to safely harness the power of sonic hedgehog in the cerebellum”.

Professor Reeves further highlights that even leaving safety aside, the possibility of finding an effective treatment for the full complement of developmental and learning problems associated with Down’s is unlikely. He says, “Down syndrome is very complex, and nobody thinks there's going to be a silver bullet that normalizes cognition. Multiple approaches will be needed.”

While these findings offer encouraging prospects that some of the brain problems associated with Down’s syndrome could be treatable in future, it is important to remember that this is a long term goal.

NHS Attribution