Can MGUS be cured by CRISPR?

Connections between MGUS and Peripheral Neuropathy:

Direct Antibody Activity**: The monoclonal protein (M protein) produced in MGUS can sometimes have antibody activity against components of the peripheral nervous system. For instance, IgM MGUS is notorious for producing antibodies that target myelin-associated glycoprotein (MAG), a protein in the myelin sheath around nerves, leading to demyelination and nerve dysfunction.
- **Autoimmune Reaction**: The M protein might trigger an autoimmune response where the immune system attacks nerve tissue.

2. **Amyloidosis**:
- In some cases, the light chains (parts of the M protein) can form amyloid deposits in nerve tissues, leading to a type of amyloid neuropathy. Amyloid deposits can physically disrupt nerve function by replacing normal tissue structure.

3. **Toxic Effects**:
- The M protein or its fragments might have direct toxic effects on nerve cells, though this mechanism is less understood and less common.

4. **Vascular Compromise**:
- In rare instances, the M protein might increase blood viscosity or cause small vessel disease, leading to reduced blood flow and oxygen to nerves, thus causing ischemic neuropathy.

CRISPR :
Gene Therapy (Experimental/Research Stage)**:
- While not yet mainstream, gene therapies aim to correct or modify the genetic mutations that drive the production of these proteins. This could potentially stop or reduce the production at its genetic source, though this is largely in experimental stages for MGUS or related conditions.

Monoclonal Gammopathy of Undetermined Significance (MGUS),

CRISPR stands for “clustered interspaced short palindromic repeats.” Biologists use the term to describe the “genetic appearance” of a system that was discovered in microbes – including bacteria and archaea – as early as 1987. For a long time, no one really understood what it did, but around 2005, researchers discovered CRISPR is an immune system. It’s used by microbes to help protect themselves from invading viruses. To stop the invaders, the microbes use CRISPR to recognize and eliminate specific trespassers.

CRISPR doesn't exist yet for treating MGUS/SMM/MM which can be associated with a number of genetic mutations in the cells that create IgM and other proteins. There are numerous papers on MGUS, IgA, IgG, IgM, neuropathies, and many others in ResearchGate. These and NIH funded publications include background info and treatments for mostly MM. MGUS and most SMM are waiting games. The risk for progression of MGUS to MM is about 1%/year, so for most people treatment is not needed. I have IgA Kappa MGUS (for 8 years, 70 yo) and some (likely associated) polyneuropathy that I "treat" by staying active, hiking, biking, woodturning. Filtering the kappa or lambda proteins from the bloodstream would decrease damage, including if someone has amyloidosis, but that dialysis would have its own issues. I have 1q21 gain, which means one of the mutations that I have is an extra gene on the long arm (q) of chromosome 21 based on my bone marrow biopsy.

Typo on my discourse: 1q21 is on chromosome 1, not on 21, which refers to the location on the chromosome.

Thank you, very much for sharing that information with me. It appears that you have the precise information needed for a CRISPR team to remove that mutation.
Some research scientist should get a grant, write a paper, and win a Nobel prize. Where do research scientists live?

I have had two nearly fatal events of DVT/PE, and have been suffering with “ idiopathic peripheral neuropathy “ for many years. If MGUS is responsible it would be much appreciated if the mutation could be identified and fixed. I am 84. There is not much time for waiting. I was very active with exercise and hobbies. No relief from that for me. Why not volunteer my squirming painful body to the advancement of science and CRISPR therapy?

CRISPR was easier for sickle cell anemia because it was one mutation on one chromosome. There are a number of different mutations that can influence MGUS turning to MM, so a much harder task. A focus right now is creating proteins that link to myeloma cells and decrease/end replication by encouraging your immune system to go after the nasty cells (a bit like how the Covid mRNA vaccines work). There are a few medicines for that now, but they are expensive, have side effects, and are mostly for later SMM and MM. Here is one article: https://pmc.ncbi.nlm.nih.gov/articles/PMC8584466/

@ewcbhc, here are some relevant articles from Mayo Clinic:
- How will CRISPR gene editing change healthcare? https://mcpress.mayoclinic.org/healthy-aging/how-will-crispr-gene-editing-change-healthcare/
- Researchers test DNA editing, recommend steps to improve accuracy https://newsnetwork.mayoclinic.org/discussion/researchers-test-dna-editing-recommend-steps-to-improve-accuracy/
- RegenBio Summit: Could a molecular scissors heal disease? https://newsnetwork.mayoclinic.org/discussion/regenbio-summit-could-a-molecular-scissors-heal-disease/

CRISPR holds much promise and hope, and this research at Mayo Clinic. I wonder if you might be eligible and interested in this Mayo clinical trial involving patients interested in CRISPR technology:
- Gene Editing Research With a Patient Centered Approach https://www.mayo.edu/research/clinical-trials/cls-20541213

Thank you, so much for your patient and thoughtful replies. I am obviously ignorant of the many obstacles involved in using CRISPR. My thought is that it might be used to prevent MGUS. That will not fix my neuropathy, but it might prevent further damage to the myelin sheaths. Repairing the damage, or growing new nerve pathways are up to my overworked stem cells.