“Monstrous” Sonic Hedgehog Reverses Down Syndrome

Finishing up on the news about the research that reversed Down syndrome-genes in genetically-engineered mice with a single injection to the brain. I recalled reading about the agent used in the treatment that had a different, and more concerning, impact. It’s another reason why I would think twice before injecting it into a newborn’s brain. 

The researchers used a compound called “SAG,” sonic hedgehog pathway agonis, which activates the sonic hedgehog pathway. The name is derided for its silliness, but there are many types of “hedgehog”-named genes. This one got its name because fruit flies with a deficiency in the protein grew spine-like protrusions. Ergo, sonic hedgehog, after the spiny-backed SEGA video game character, Sonic the Hedgehog.

A SAG compound was injected into the brains of genetically-engineered mice with mixed results: typically-sized cerebellums that still showed a deficiency in neuron signalling, and developed hippocampus, aiding in learning and memory, but no prefrontol cortex change, where planning and decision-making occurs. In the announcement, the researchers cautioned that its use in humans was still far off, in part due to concerns about the treatment’s potential for triggering the growth of cancers.

When I read the news about the sonic hedgehog injection it made me recall a book I recently read about DNA: The Violinist’s Thumb. Here’s what that book has to say about sonic hedgehog and why the researchers are right to be cautious if the injection were to be introduced into the treatment of humans with Down syndrome:

[S]HH–as scientists who detest the name refer to sonic hedgehog–helps control the body’s left-right symmetry. SHH does so by setting up a GPS gradient. When we’re still a ball of protoplasm, the incipient spinal column that forms our midline starts to secrete the protein sonic produces. Nearby cells absorb lots of it, faraway cells much less. Based on how much protein they absorb, cells “know” exactly where they are in relation to the midline, and therefore know that type of cell they should become.

But if … SHH fails … the gradient doesn’t set up properly. Cells can’t figure out their longitude in relation to the midline, and organs start to grow in abnormal, even monstrous ways. In severe cases, the brain doesn’t divide into right and left halves; it ends up as one big, undifferentiated blob. … But the most distressing violations of symmetry appear on the face. Chickens with too much sonic have faces with extra-wide midlines, sometimes so wide that two beaks form. (Other animals get two noses.)

A simple Google search for “too much sonic hedgehog protein” led me to some of these “monstrous” images, and an interesting news story.

Frank and Louie
Photo credit: Steven Senne, Associated Press

Apparently, this effect of too much sonic happens often enough in cats to result in a name for the phenomena: Janus cats, named after the Roman two-faced god (whose image I have featured in posts about apparent hypocrisy and double standards). Most all Janus-faced animals are either stillborn or short-lived. But, there is one cat, Frank and Louie, in Massachusetts who has lived over twelve years.

The research headlined as a “reversal” or “cure” of Down syndrome is anything but. At the same time, it does show potential as a means for cognitive treatment. Moreover, when reading about the researchers comparing the performance of navigating water mazes by the treated mice against untreated genetically-engineered mice and against typical mice, one has to respect the amount of time and effort they are committing to develop possible treatments.

But, given the “monstrous” impacts–Frank and Louie notwithstanding–we should not overlook the caution of injecting a newborn’s brain with added sonic hedgehog should that treatment actually reach clinical trials for humans.