CRISPR-Cpf1 Corrects Duchenne Mutations, Restores Dystrophin Expression, UT Study Shows

CRISPR-Cpf1 Corrects Duchenne Mutations, Restores Dystrophin Expression, UT Study Shows

Researchers from the University of Texas Southwestern Medical Center in Dallas have corrected Duchenne muscular dystrophy (DMD) mutations in human cells and experimental animal models using a new genome editing method called CRISPR-Cpf1. These new findings offer hope in permanently eliminating genetic mutations and rescue abnormalities linked to DMD.

The study, “CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice,” appeared in the journal Science Advances.

Researchers had previously shown that a genome editing method called CRISPR-Cas9 could correct genetic defects that characterize DMD. This team recently received a grant from Parent Project Muscular Dystrophy (PPMD) to continue its studies and identify possible risks associated with the CRISPR-Cas9 method in a clinical setting.

In this latest study, the team used CRISPR-Cpf1 to cut out and repair mutations associated with DMD. This gene-editing method variant has several improvements compared to the earlier method. Cpf1 is much smaller than Cas9 (the enzyme that cuts DNA), making it easier to deliver to the target cells. It is also more flexible in terms of possible therapeutic use.

“We took patient-derived cells that had the most common mutation responsible for Duchenne muscular dystrophy and we corrected them in vitro to restore production of the missing dystrophin protein in the cells. This work provides us with a promising new tool in the CRISPR toolbox,” the study’s senior author, Eric Olson, MD, said in a press release.

“There will be some genes that may be difficult to edit with Cas9 but may be easier to modify with Cpf1, or vice versa,” added Olson, chairman of molecular biology and co-director of the UT Southwestern Wellstone Muscular Dystrophy Cooperative Research Center. “The two proteins have different biochemical properties and recognize different DNA sequences, so these properties create more options for gene-editing.”

DMD is caused by mutations on the gene that encodes the dystrophin protein, which is essential for correct muscle movements. Mutation on its gene leads to a decrease of its expression and loss of muscle strength.

“By either skipping a mutation region or precisely repairing a mutation in the gene, CRISPR-Cpf1-mediated genome editing not only corrects Duchenne muscular dystrophy mutations but also improves muscle contractility and strength,” said co-author Rhonda Bassel-Duby.

Using this new method, researchers showed that it was possible to efficiently and specifically correct common mutations found in the dystrophin gene, restoring the normal protein expression. They showed this not only in patient-derived stem cells carrying DMD mutations, but also an animal model of DMD.

The most common fatal genetic disorder diagnosed in childhood, DMD affects roughly one in every 3,500 live male births. Because the Duchenne gene is found on the X-chromosome, it primarily affects boys; however, it occurs across all races and cultures. Duchenne results in progressive loss of strength and is caused by a mutation in the gene that encodes for dystrophin.

“CRISPR-Cpf1 gene-editing can be applied to a vast number of mutations in the dystrophin gene,” said Olson. “Our goal is to permanently correct the underlying genetic causes of this terrible disease, and this research brings us closer to realizing that end.”

 

17 comments

  1. Brenda Lewis says:

    How exciting!!! I have Hereditary Spastic Paraplegia, maybe they could find a miracle for that! Spg4 mutation.

  2. Jose L Zamora says:

    When this drug, CRISPR, could be approved in USA and,
    what can we do to register our grandson (7 yo) who has been diagnosed with DMD to be part of a CLINICAL TRIAL? We live in Brownsville, TX
    Jonathan is still running and shows a great stamina but analysis and the way he walks confirm the diagnose.

    God Bless You All

    • Alice Melao says:

      I am afraid this potential new therapy is still under research and it still requires to be proven safe and effective for use in humans.

  3. Pratik Deshmane says:

    I have Muscular dystrophy. But still I am able to walk but when I ascend the stairs then only I havr to take support. So will this drug help me?

    • Alice Melao says:

      This therapy has the potential to correct protein deficiencies cause by genetic mutations. Given so, if this describes you medical condition you could potentially benefit from CRISPR therapeutic strategy. But it is important to stress that these therapeutic findings resulted from an experimental setting still requiring to be further explored and confirmed in a real clinical setting.

  4. jeff says:

    I’ve been following CRISPR news for years, it’s so exciting to see how far it has come in a short amount of time. At 45 and having LGMD I am failing fast. I sure hope this gets fast track approved and cures are achieved rapidly.

  5. Natalie Martinez says:

    This is very exciting news!!! My 8 yo son is the 3rd in my family to be diagnosed with this terrible disease. This was always my fear and when it was realized…….I have NEVER been so petrified and terrified. As I know all parents are when given the diagnosis. I pray everyday for his healing or for God to bring about a cure. ??

  6. arati says:

    What timeline in your opinion will this therapy be ready for use? Even a range will be helpful and we can pray for it to expedite and get approvals

    • Alice Melão says:

      It is very difficult to do such a prediction. Clinical confirmations of a drug safety and efficacy can take several years. Urgent need of therapies for specific conditions can help expedite these processes, but usually it still takes a considerable amount of time. It is really impossible to do an accurate time estimate on this matter, I am afraid.

  7. Lakshmi says:

    This is really very good to hear for parents like me , but i am very concerned on the timeline ..can any one say appx how long does it take to get approvals and also how can we track the developments or phases of this therapy ? Please help !

    • Alice Melão says:

      According with the article information CRISP-Cpf1 was used to correct the effects of deletion of exons 48 to 50 of DMD gene.

      • Sue Tamatimu says:

        Hi Alice,
        My son has deletion 48-50, diagnosed with DMD at 4 years old. He is 13 now and on prednisolone. He is still mobile but not much. I can see he is weakening. Reading the results of these clinical trials gives me some comfort but knowing how long these things takes stops me from jumping up and down with joy. I’d really like to receive updates on your timeline if at all possible.
        Thanks,
        Sue

    • Brenda Lewis says:

      Great news!!! Could they try anything for Hereditary Spastic Paraplegia? My gene mutation is spg4 ( most common). Please consider,I a losing hope!

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