Blocking Notch Pathway Leads to New Route to Hair Cell Regeneration to Restore Hearing

Discussion in 'Research News' started by exodus, Dec 22, 2014.

    1. exodus

      exodus Member

      Tinnitus Since:
      An interesting finding

      Sensory hair cell loss is the major cause of hearing loss and balance disorders. The postnatal mammalian inner ear harbors progenitor cells which have the potential for hair cell regeneration and hearing recovery, but the mechanisms that control their proliferation and hair cell regeneration are yet to be determined. Now scientists from the Eaton-Peabody Laboratories at Massachusetts Eye and Ear/Harvard Medical School and Fudan University, Shanghai, China, have shown that blocking the Notch pathway, known to control the elaborate hair cell distribution in the inner ear, plays an essential role that determines cochlear progenitor cell proliferation capacity. Their research was published today in PNAS Early Edition.

      "A high level of Notch activity prevents progenitor cell division and hair cell regeneration in the postnatal inner ear," said Zheng-Yi Chen, Ph.D., of the Eaton-Peabody Laboratories at Mass. Eye and Ear and an Associate Professor of Otology and Laryngology at Harvard Medical School. "We learned something new about this mechanism. It is known that inhibition of Notch activity can convert inner ear supporting cells to hair cells. In this paper, we have shown that Notch inhibition also promotes cell division. Under the condition, the inner ear progenitor cells re-enter cell division to regenerate hair cells in postnatal cochlea. This study thus provides a new route to block Notch activity to increase progenitor cell population by cell division, and to regenerate new hair cells. Our work could have potential in leading to developing new strategies to achieve hair cell regeneration for hearing restoration."

      The researchers show that Notch inhibition initiates proliferation of supporting cells that give rise to new hair cells in postnatal mouse cochlea in vivo and in vitro. Through lineage tracing, they identified that a majority of the proliferating supporting cells and cell division-generated hair cells induced by Notch inhibition are originated from the Wnt-responsive leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5+) progenitor cells. They demonstrated that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5+ progenitor cells to mitotically generate new hair cells.

      "Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways," Dr. Chen said.
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    2. tomytl

      tomytl Member Benefactor

      Tinnitus Since:
      10 Years
      Cause of Tinnitus:
      yes, this researcher is very top notch. It's the one who made some very important discoveries back in 2005
      with RB1 gene and hair cell regeneration. He is working close with Dr. Edge, who is also participate with
      Audion Therapeutics. They are very optimistic about their research, so maybe we will see some progress soon.
    3. OptimusPrimed

      OptimusPrimed Member Benefactor

      Tinnitus Since:
      Cause of Tinnitus:
      Acoustic trauma - Repeated gun blasts
      Hair cell regeneration is not a matter of if, but when. Hopefully sooner rather than later. Imagine an ear drop that restored hearing and eliminated the tinnitus associated with that frequency loss. Dreaded scar tissue!
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    4. Peter61

      Peter61 Member

      The Netherlands
      Tinnitus Since:
      This is real good news. It gives me hope for being able to enjoy silence again in the future, and it's exactly this hope that I need to carry on. Thank God for scientists like Dr. Zheng-Yi Chen.
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    5. skoupidis

      skoupidis Member

      Tinnitus Since:
      Cause of Tinnitus:
      Acoustic trauma or mvc
      Ok, it is good news but only in theory. Several articles about cell regeneration are published for some time now. I think it is time to move the subject a bit further... There is quite a distance from theory to practice.

      However, China makes me optimistic in such things, I don't know why, but I do believe the first cure will come from there. And hopefully quicker than we imagine.
    6. tomytl

      tomytl Member Benefactor

      Tinnitus Since:
      10 Years
      Cause of Tinnitus:
      Yes, it's always a long distance from discovery to a causal and save treatment. When I got hearing loss in 2003, you almost didn't find any infos about. This changed very much... now there a labs and consortiums doing exclusive research on hair cell regeneration. While we talk about, the first person got some gene therapy with an approach of HCR they discovered in 2005.... so it took almost 10 years from discovery to the human trial... that's how medicine is.
      But an other exciting fact about HCR is, they are doing research with different approaches, so there is gene therapy, stem cells, molecular therapy... all might have a potential ....
      So it's not the case, that this research stands always at the same point, it's moving and some labs are working really hard for it...
      Let's hope that the running trial from Novartis /Genvec bring us some positive results... a positive result would be, secure delivery and some few dB on hearing recovery. I wish it for the volunteers participating and for all people suffering from hearing loss...

      Some seriouse researchers believe, that a cure applicable on human isn't in a not to far future.

      Greets Tom
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