How a one-time CRISPR shot could obliterate lower back pain

Sep 18, 2019

The National Science Academy in the US has hosted its first International Commission meeting to discuss Human Genome Editing and its clinical use. Controversial topics such as the use of CRISPR for human sperm, eggs, and fertilized ova was covered after He Jiankui, a Chinese researcher, brought about the birth of twins via CRISPR.

In terms of CRISPR, there’s only one human clinical trial that’s being done, with the patient meeting up with the media to answer queries regarding edited cells to combat sickle cell disease. Other studies are still under the pre-clinical phase, with organoids, human cells, and animal models.

CRISPR holds promise that a single injection may be enough to stop the inflammation that leads to lower back pain long term. A Human Gene Therapy report states that CRISPR can make it possible by shutting off the cytokine signals of the patient’s immune system.

Lower back pain is affecting more than 65 million individuals in the US, most of which are a form of DDD, or degenerative disc disease. Here, cartilage discs that act as shock absorbers wear out, therefore making it harder for the patient to bend and flex.

DDD is actually considered part of aging and not a disease, as the spinal discs grow smaller and lose the ability to retain water. About 85% of the whole US population aged 50 and up suffer from it, with most cases being asymptomatic. Signs can range from pain flashes to numbness and weakness in the legs, which can disable and become chronic.

Current treatment only addresses the pain but not the underlying source. Anti-inflammatory drugs such as steroids, ibuprofen or aspirin are given, as well as physical therapy, or surgery to remove defective discs or fuse disc parts.

Alternative therapies for lower back pain may include massage, homeopathy, yoga and acupuncture. Herbal remedies such as the extract of white willow bark (nature’s aspirin), S-adenosylmethionine and the Devil’s Claw, or Harpagophytum, may be given.

Environment or Genetic Predisposition?

In the 90’s, it was largely believed that the environment was a defining factor on how an individual might acquire DDD. Factors such as driving or sitting for long periods of time, constant heavy lifting, being exposed to vibrations, and smoking were attributed to the condition.

A study by TwinsUK in 1999 then proved the world wrong by showing that degenerative disc disease may have been due to heritability. The report outlined in detail how an individual’s genes could make up a large portion of the condition’s risk and variables.

Genome wide association studies, otherwise known as GWAS, started in 2008 and helped with variation site patterns and human genome sequencing as per the twin studies.

Today’s research centers around possible candidates that can form an extracellular matrix (the glue) via proteins that could bind the cartilage cells and inflammation. The possible list of proteins include TNF, or tumor necrosis factor, a few ILS or interleukins, glycoproteins, vitamin D receptors, collagens, and an inteferon.

The CRISPR

Intervertebral discs that are inflamed may prove to be resistant against many traditional treatments. Back surgery does not mean 100% success, and remedies only bring about temporary relief. Meanwhile, newer therapies such as growth factors diffuse, and stem cells quickly degrade when faced with a cytokine-rich environment.

Researchers at the Utah University Department of Orthopedics, Oncological Sciences and Biomedical Engineering, headed by Robert Bowles, are exploring ways on how to edit the genes of cells collected from the spinal disc using the CRISPR epigenome system. Epi means that the genes responsible for causing inflammation are altered.

Results from animal studies have yielded immune system proteins that can affect back pain, including interferon-c, interleukins 17, 12, 10, 8, 6, 4, 2, 1b and 1a and tumor necrosis factor for DDD. Drugs that contain TNF receptors, i.e., monoclonal antibodies Humira and Remicaid, are already being sold on the market. These medications treat plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and more.

CRISPR research is trying for a long-lasting solution since Humira is self-administered on a weekly basis and Remicade has to be given every couple of weeks or so.

Researchers are working on two major cytokines, IL-1 beta and TNF alpha in their CRISPR approach to treating DDD. Studies have proven that these proteins ignite disc cells with extracellular matrix degradation, inflammation and apoptosis. A protein called NF-kB activates the genes that control the actions.

Bowles and team then tried targeting NF-kB instead of trying to block the two cytokines using monoclonal antibodies, with a goal that the treatment had to be more specific than Humira or Remicade.

For proof of concept that their method could work, the team collected cells from patients who underwent back surgery. The waste that originates from the vertebral discs’ gel-like inner part, along with the nucleus pulposus were studied.

CRISPR dampened a protein called KRAB, or Kruppel associated box, which led to the inhibition of the NF-kB gene that controlled the 2 cytokines. The cascade stopped inflammation and reduced the production of cytokines.

Researchers also wrote about viral vectors, such as the lentivirus or disabled HIV being the key to long-term and possibly permanent solution. One-time delivery via CRISPR can finally give patients who suffer from DDD promising results.

In tests, the CRISPR cargo stopped extracellular matrix destruction, improved cell survival, and reduced inflammation. With these results, the team thinks that they can come up with an injectable gene therapy that could effectively slow down DDD.

In 2018, the researchers proposed practical ways on how to treat back pain on patients suffering from DDD using CRISPR. While studies show that intervertebral disc cells are rare, there have been other trials that target the dorsal root ganglia, which also works.

There are concerns that the CRISPR system could damage, target or kill future genes and cells, or pass on to future generations. But lower back intervention has a lower risk of reaching the eggs or sperm.

Treating DDD using CRISPR still has a long way to go before it’s made available to the public. The potential of treating chronic back pain with a single injection is an interesting topic to the millions who suffer from chronic lower back pain.

 

To your health,

The Healing Miracle Team

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3 Comments

  1. Ellen

    is there somewhere in this article for novices where it explains what CRISPR stands for?

    Reply
    • THM Team

      Along with our blogs, we also recommend that everyone tries to find other sources as well. Google will provide many resources.

      Reply
  2. Samantha York

    Yes! Finally, some useful information I have been longing for. Thank you.

    Reply

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