CRISPR – Does it hold promise for Treatment of Fragile X Syndrome?

CRISPR

There’s been a lot of press concerning a new biotechnology called CRISPR/Cas9, or simply CRISPR. This technology, which is based on the discovery of naturally-occurring bacterial defense mechanisms, has attracted an enormous amount of biotech investment. It has also excited the imaginations of scientists, clinicians, and rare disease advocates everywhere. How might CRISPR be applied to Fragile X syndrome? CRISPR offers the tantalizing possibility of “editing” genes very precisely, and it could (theoretically) excise the methylated trinucleotide repeat sequence from Fragile X cells, rendering them entirely normal.

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CRISPR Reactivation of the Fragile X Gene

Todd-Haenfler

“We are trying to target the first event that goes wrong in Fragile X syndrome”, says Todd, “One reason our previous attempts to develop treatments for Fragile X syndrome have failed is that they’ve tried to target the downstream effects of losing the Fragile X protein. The protein does many things… bypassing all the functions that it normally takes care of has proven difficult from a pharmacologic perspective.”

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University of Michigan researcher Peter Todd, MD, PhD, Aims to Selectively Turn the Fragile X Gene Back on in Human Cells

Dr. Haenfler and Dr. Todd

Fish like salmon are born in fresh water streams and rivers. When the time comes for them to breed, they return to the stream of their birth to lay eggs in the same spot where they were born. To accomplish this, they must swim upstream against the current or flow of the stream. Taking a page out of the salmon DNA playbook, University of Michigan scientists Peter Todd, MD, PhD, and postdoctoral fellow Jill Haenfler, Ph.D., are exploring unchartered waters to find a cure for Fragile X Syndrome. The researchers are adapting CRISPR research to reactivate the FMR1 gene, which provides instructions for making a protein called FMRP — needed for normal brain development.

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Fragile X Research Impacted by a Small Group of Thoughtful, Committed Citizens

Todd-Haenfler

Theirs was an effort by a small group of thoughtful, committed members of the Fragile X Association of Michigan (FXAM) to be sure. The entire project took months! But it was hard work well worth the effort. After writing and revising (and revising), FXAM was awarded a $35,000 grant which the Michigan Fragile X group will now direct to Dr. Todd’s ongoing Fragile X research involving CRISPR!

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Retinoic Acid Signaling is Blocked by Fragile X Mutation

Human Neurons

With a 2013-2014 FRAXA Research Grant, Principal Investigator Marius Wernig, PhD and FRAXA Fellow Samuele Marro, PhD at Stanford University found that the Fragile X mutation impairs homeostatic plasticity in human neurons, by blocking synaptic retinoic acid signaling. Retinoic acid is a metabolite of Vitamin A. The system they have developed could provide a powerful new cellular biomarker for screening many treatment approaches.

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Takeaways from Fragile X Advocacy Day

In the first week of March I attended my first Fragile X Advocacy Day to meet with many of the Massachusetts delegation to Congress. While this was my first time advocating for Fragile X research, I’ve been a longtime lung cancer research advocate and have met with many of the same representatives in the past. It was a pleasure to meet with many of the families as my participation in Advocacy Day was in the spirit of “we are all in this together”.

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Fragile X Syndrome Research & Treatment • FRAXA Research Foundation – Finding a Cure for Fragile X

FRAXA Research Foundation’s mission is to find effective treatments and ultimately a cure for Fragile X syndrome. Fragile X syndrome is the most common inherited cause of autism and intellectual disabilities. We directly fund research grants and fellowships at top universities around the world. We partner with biomedical and pharmaceutical companies, large and small, to bridge the gap between research discoveries and actual treatments.

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