Inhibiting Enzyme Can Reverse Myelin Damage, Improve Limb Function, Mouse Study Shows

Inhibiting Enzyme Can Reverse Myelin Damage, Improve Limb Function, Mouse Study Shows

Inhibiting an enzyme responsible for turning genes on and off can reverse damage to the myelin sheath that protects nerve cells, improving limb function, a multiple sclerosis-related study in mice shows.

The research, which involved mice with sciatic nerve damage rather than MS, was published in the journal Nature Medicine. Its title is “A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration.

Damage to the myelin sheath leads to such MS-related problems as muscle stiffness and weakness, fatigue and pain.

A team at the Cincinnati Children’s Hospital Medical Center and other researchers decided to look for compounds that could inhibit enzymes responsible for turning genes on and off.

Scientists dub the turning-on and -off process epigenetic regulation. The process does not interfere with a gene’s DNA sequence. It works by adding or removing an epigenetic mark from a DNA sequence — much like adding or removing a clothes pin .

The team tested the compounds they thought had potential in mice with injured sciatic nerves, which run from the lower back to the lower legs. Many of the compounds were approved cancer treatments.

A key finding was that compounds that can inhibit a particular epigenetic enzyme reversed the mice’s myelin damage and improved their ability to move. The enzyme, histone deacetylase 3, or HDAC3, slows myelin production when nerves are forming or after they have been injured.

The braking leads to the formation of a very thin layer of myelin or in some places no layer at all. The result is impaired communication between the peripheral nervous system and the limbs and organs. The peripheral nervous system consists of all nerves outside the brain and spinal cord.

“Remarkably, temporary inhibition of HDAC3 robustly accelerated the formation of myelin that helps insulate peripheral nerves,” Dr. Q. Richard Lu, the director of the Cincinnati Children’s Brain Tumor Center, said in a press release. “This promoted functional recovery in the animals after peripheral nerve injury,” said Lu, the study’s lead author.

Blocking HDAC3 must be precise, the researchers said. Inhibiting it for too long leads to excessive myelin growth, resulting in overly thick nerve cell insulation that can also cause functional problems.

The team timed its HDAC3 inhibitor treatment to a critical phase of nerve regeneration in the mouse model. The treatment led to just enough myelin to restore the mice’s function — but not too much.

Researchers have begun testing their findings in mouse models of other diseases caused by myelin damage, such as MS. If the results are promising, they plan to start Phase 1 clinical trials of the treatment in MS patients.

 

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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121 comments

  1. Joshua Sully says:

    Wow that’s amazing and I’m sure it does wonders as a new treatment to help restore the myelin and regain most function in limbs.

  2. Jim says:

    I feel as though researchers are getting closer and closer to a cure. However, rebuilding our myelin sheath so we can function better would be wonderful.

  3. Dave Carney says:

    They’re getting so close, Maybe some day this will be bad dream. I have PPMS went for my third dose of ocrevus today. Everybody hang in there.

  4. Pat hawkins says:

    This is what they should of been trying to do the whole time, something to rebuild ur myelin and revolt as a cure,not poison meds…..silly!!!!

    • Karen Mayrand says:

      I so agree, enough of the medications that don’t do a heck of a lot but cause other serious health problems…Maybe all of are hopes and dreams will finely be answered in the very near future..

    • Charles says:

      I know my daughter would agree with you. All the leading meds just have been total failures for her. Constant migraines and nausea. She has made more progress with a natural protocol.

  5. Laura says:

    I am interested in the clinical trial. I have had progressive MS for about 20 years. I have never taken any drugs, only used natural interventions such as diet and supplements. My walking is completely dependent upon a walker and I use a wheelchair when necessary. Would love to regain my mobility. I am 66 years old. This sounds very promising!

    • Robin Prince says:

      I take Copaxone but i also have to use a walker and a wheel chair and im 54 yrs old,i was told i have MS in 1994

  6. Kevin Martin says:

    How do i get involved in the trial research i have MS with myelin damage causing perralouses on my left side. Can not walk more then 10 minutes.

  7. Annette Cusick says:

    Like all exciting announcements about potential progress, this will take another decade to begin and finish trials. I have MS and must have heard a dozen things that never amounted to much. Hopefully we will see progress- and if not at least others will get help later. I have a feeling something better will come along way before this is available.

  8. Luvena says:

    My husband was recently diagnosed with MS but they are saying he has had signs from at least 2013 or earlier. I would love for him to be part of this study. We are in Ohio.

  9. Lou Wade says:

    My 53 year old son has had it since he was 18. He’s had/has a super pubic catheter (loss of all uninary control and partial bowl control). He also has some brain damage due to a very difficult birth. He’s also a great big gentle teddy bear that people love. Sure would be great to get him enrolled in a trial. Any chance?

  10. Barry Paxton says:

    Would love to participate in your clinical trials. I live outside of Richmond,Va. I have MS,70 years old and have difficulty walking.

  11. Ruth Santiago says:

    Hi I am from Texas, I would love to participate in this trial. I am only 38 and having so much difficult walking. I am tired od being tired and just seems like nothing helps.

  12. Christine Barfield says:

    I would love to be a party apart in the trial. I have had MS for 17 years and no longer walk without assistance. It’s very frustrating and my legs are my worst part of my body

  13. Bill Rogers says:

    I am a 59 yr old male, Dx in 2009 with RRMS. Recently started with Ocrevus in Jan. 2018. I am extremely interested in being a part of this trial.

  14. Lisa wilcher says:

    I would love to try this. I live in Cincinnati my daughter works at Children’s Hospital would really like more information on this

  15. Davey sessions says:

    Please contact me to be included in your clinical trial.
    I am 60 and was diagnosed 4 years ago as have seen my limbs stiffen.

  16. Jamina Good says:

    I would love to be apart of this trial. My neuro said according to my MRI I’ve had MS since my 20’s and was dx at 38. I’m in Tucson, AZ. Dealing with limited mobility, fatigue and brain fog. Thank You so much!

  17. Vance Batson says:

    I miss being a strong hard worker. Now I’m in a wheelchair. I changed my diet as soon as I was diagnosed 3 years ago I would like to be involved with the clinical trial please

  18. Frank Sanchez says:

    This would be great. I’m in Southern Ca. I was diagnosed 15 years ago. Trying to stay active and go to the gym. 65 years old. My younger brother passed away 2 years ago due to MS. My niece also has MS.
    A trial participation would be wonderful.

  19. Teresa's mccrady says:

    I would. Do this trial for the chance to see some improvement In My Walking and the opportunity to help the research.

  20. Jessica says:

    Just FYI, the image you are using for this article shows Schwann cells myelinating that neuron, not oligodendrocytes. Schwann cells are only in the PNS, not the CNS, and are not involved in MS.

  21. Deborah Lange says:

    I would love to be considered in this trial. I was do in 2013 with RRMS, and am 65 years old.
    Thank You

  22. Mark Motob says:

    My wife was diagnosed almost 2 years ago. She has fatigue and legs feel heavy at times. I would love to have her assist in the clinical trials. How can we get more information about this study.
    Any info would be greatly appreciated.
    Thank you.

  23. Jean Scott says:

    I would love more information. Was diagnosed in the 80’s and refused meds that were so strong and not proven to be effective as a cure.

  24. Arturo García says:

    I live un Guadalajara México how can i get involved un this trial my phone number Is 3314174414 please ssombody call me thanks Arturo García

  25. Lisa Petch says:

    I am 52 And was diagnosed with PPMS in Sept 2011. My own personal 911. Finally something that makes sense! Would be thrilled to be considered. I can still walk unassisted. But there is still plenty of pain and spacity in right leg. But left is catching up.

  26. Debbie says:

    This is the most promising news since I got the diagnosis (progressive type, 14 years ago).
    When are human trials?
    Where can I sign up?

  27. Jessica says:

    I was diagnosed with RRMS in March 2010… I would be awesome if this will help people like me with MS. I would definitely participate in the clinical trial to be able to help these researchers to help others.

  28. Terry says:

    I have been diagnosed with Guillain-Barre Syndrome which also is a serious nerve damage disease. Would love to think this medicine would be available to those with the many autoimmune diseases that Eat the sheath off the nerves.. I was instantly paralyzed and am in a lot of nerve pain, called neuropathy.

  29. Patricia LaPorta says:

    Finally, a glimmer of hope!!!!! Interested in the trial, if one in the area….please keep the information coming….Had no DMD’s, M>S> since the ’90’s..I’m 72, get around w/walker……

  30. Kathy Quick says:

    Arizona resident. Dx 2000, 55 this year. Would love to be part of trial. The possibility of walking and getting dressed without falling is such a wonderful dream.

  31. Scott Van De Grift says:

    This sounds like a trial i need to be on I’ve moved from walking 3 miles a day to wheel chair full time in 6 years. If this can help and heal myelin I’m all for it

  32. Betty Fertig says:

    I have had ppms since 1985 and the only medication I have used is ocrevus. This trial, if successful, would be a dream come true. I am in a wheelchair most of the time, using a walker for short trips. I hope to hear from you soon.
    Thank you.

  33. Mike Johnson says:

    Diagnosed in 2015 at 59 with the adult onset myelin disease leukodystrophy . Is this a potential future treatment therapy? Because this diesease is generic, I am very interested in the trial of the drug treatment if possible.

  34. Brandon garces says:

    Please im only 23 and il using a walking frame i don’t have a life mybe this treatment is for me please put me on trials

  35. Karen Hagaman says:

    I am a 65 yr old female from Peoria IL. I was diagnosed in 2015 and like to be apart the clinical trial. I have recently started Ocrevus after a I tested positive for the JC virus. Prior med was Tecfedra.

  36. Rachel Lukes says:

    I have ms and on this medication, everything going great but only did the first two infusions then 6 months later I got another dose but so far doing good

  37. Kathy Oakley says:

    I would Love to be part of the trial ! I am a 57 year old female who was diagnosed in 2010 . I would honor the chance to help make this disease disappear for everyone that has been touched by it .

  38. Jerry Stevens says:

    I have the PPMS beast and am on the Ocrevus infusion plan; however, since all the Ocrevus is supposed to do is stop the degeneration, I would like to participate! I was documented with MS in April, 1979 so my nerves aren’t in great shape. We are in the Houston area but preparing to sell our house and move to Corpus but I’m in if wanted!!!

  39. Bill Allard says:

    I would be elated to be included in this trial. I was diagnosed with MS in 2006, and have not walked for two years!!!

  40. Monica says:

    I would LOVE to be part of the trials. Diagnosed in ’13 and have used a cane or walker since. Left thigh is affected. Also have foot-drop. I’d give anything to be able to walk again! I live in Michigan.

  41. Mike M says:

    I would like to know more about how to take part in the study. I was diagnosed in Jan 2018. I get some leg pain and numbness all over, but I still have good movement. I live in Mississippi.

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