Sound Pharmaceuticals (SPI-5557 & SPI-1005)

Discussion in 'Research News' started by joe, Jan 26, 2012.

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    1. joe

      joe Member

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      UK
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    2. Markku
      Inspired

      Markku Director Staff Benefactor Hall of Fame Team Trobalt Team Tech Team Awareness Team Research

      Tinnitus Since:
      04/2010
      Cause of Tinnitus:
      Syringing
      http://www.nature.com/scibx/journal/v2/n17/full/scibx.2009.688.html

      Stepping toward a therapy

      Developing a therapeutic to target miRNA-96 will likely pose two main challenges: delivery to cells in the inner ear and avoidance of side effects associated with interfering with non–hearing-related genes potentially regulated by the miRNA.

      Before either of those issues can be addressed, however, 2131e Feinstein, CSO of Quark Pharmaceuticals Inc., said a key next step is determining whether the hearing loss phenotype is caused by a loss-of-function mutation, in which the miRNA-96 mutant cannot bind its original targets, or a gain-of-function mutation, in which the miRNA-96 mutant binds a new target instead of or in addition to its original targets.
      In addition, Quark president and CEO Daniel Zurr said controlled, local delivery of an miRNA-96-targeting therapeutic to the hair cells will be essential. “Because miRNAs can affect the expression of many target genes, there exists the potential for unwanted modulation of off-target genes in healthy tissue if delivery is not highly specific,” he said.

      Quark has a small interfering RNA molecule in preclinical development against an undisclosed target to treat acute hearing loss associated with ototoxicity and acoustic trauma.
      Jonathan Kil, president and CEO of Sound Pharmaceuticals Inc., thinks targeting a single miRNA such as miRNA-96 to treat age-related hearing loss could be a tall order. “Age-related hearing loss is a multi-factorial disease with a complex underlying biology, and it's not clear that targeting a single miRNA like miRNA-96 is going to be sufficient to reduce or reverse disease,” he said.

      Sound Pharmaceuticals has two orally available small molecules, both inducers of glutathione peroxidase (GPX) antioxidant activity, in Phase II testing: SPI-1005 to treat noise-induced hearing loss and SPI-3005 to treat chemotherapy-induced hearing loss.

      The company's SPI-5557, a locally injected siRNA against cyclin-dependent kinase inhibitor 1B (CDKN1B; p27; Kip1), is in preclinical development to induce regeneration of cochlear cells and treat deafness. Kil and colleagues have shown in mice that knocking out p27, a growth inhibitory protein, can induce cell proliferation and hair cell regeneration in the inner ear.

      Regardless of therapeutic strategy, Thomas Meyer, founder and managing director of Auris Medical AG, said the indication itself poses multiple challenges. Age-related hearing is a slowly progressing condition that generally lacks an identifiable therapeutic window, he noted.

      “Because age-related hearing loss usually progresses at an average rate of only one to two decibels per year, the patient is often unaware there's a problem until the disease has advanced so far that any type of treatment may be too late,” Meyer said. “In such a situation, a preventive therapeutic strategy might a priori be more promising. However, it's unclear whether people would accept long-term treatment for a problem that would materialize only in the distant future and not with certainty,” he added.

      Auris is developing therapies for acute hearing loss. “Our focus is on acute hearing loss that results from acoustic trauma or other cochlear stress factors like viral infections and vascular disturbances. Those conditions are generally rarer than age-related hearing loss but potentially more amenable to treatment, especially in an emergency setting,” said Meyer.

      The company's AM-111, a cell-permeable peptide that inhibits the c-jun N-terminal kinase (JNK) pathway and is delivered by injection through the eardrum, is in a Phase IIb trial in Europe to treat acute hearing loss. Targeting the JNK pathway has an antiapoptotic effect and thus potentially prevents damaged hair cells from dying.
      Steel noted that she isn't married to any one therapeutic approach to modulating miRNA-96. “Our future work to elucidate the targets of miRNA-96 could provide us with genes and proteins that might be targeted directly by small molecules to trigger regeneration and treat some forms of hearing loss,” she said. “In any case, the therapeutic goal remains to stop progressive degeneration of hair cells that can cause age-related and environmental hearing impairment.”
       
    3. mick

      mick Member Benefactor

      Location:
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      SEATTLE, Nov. 5, 2013 /PRNewswire/ -- Sound Pharmaceuticals (SPI) has successfully completed enrollment of its Phase 2 clinical trial with SPI-1005 at the University of Florida. This study enrolled 80 healthy subjects with normal or slight hearing loss and exposed the volunteer to calibrated music using an iPod®and insert earphones. The sound level was established based on prior human studies where a slight temporary auditory threshold shift (TTS) was safely induced. The listeners were randomized to either placebo or SPI-1005 and treated before and after music exposure. The level of TTS was determined at several time points after the music exposure and all subjects and investigators were blinded to the intervention. SPI-1005 is an oral capsule that contains ebselen, a synthetic molecule that mimics and induces the activity of Glutathione Peroxidase (GPx), a critical enzyme in the inner ear that protects it from damage caused by loud sounds or noise. In preclinical studies, ebselen treatment was shown to improve GPx levels within critical cochlear structures thereby reducing the TTS induced by intense noise. Ebselen is also under clinical investigation for chemotherapy induced ototoxicity in adult cancer patients, a disease that involves both hearing loss and tinnitus. "Completing this proof of concept study is a significant milestone for SPI and we are pleased with the outcome," said Jonathan Kil, MD, Chief Medical Officer. SPI is a privately held biopharmaceutical company in Seattle with a focus on developing the first drugs for the prevention and treatment of hearing loss. "These data will be used to support our active IND with the FDA for the prevention and treatment of noise induced hearing loss," said Eric Lynch, PhD, President. Details of the study can be viewed online at www.clinicaltrials.gov by searching SPI-1005, visiting www.soundpharma.com or by calling Eric Lynch at 206-634-2559.
      SOURCE Sound Pharmaceuticals


      RELATED LINKS
      http://www.soundpharma.com
       
    4. Hudson
      Cowboy

      Hudson Member Benefactor

      Tinnitus Since:
      2003
      I have been following Sound Pharmaceuticals since they first started in 2003. It's good to see them completing a Phase II study. I have noticed that their "Regeneration" product line has increased in it's progress, which is cool as well. It would be really awesome to have a pill that we could pop before going to a place with loud noise. I think it would be comforting to have that option along with ear plugs to help protect against further degradation of hearing.
       
    5. Hudson
      Cowboy

      Hudson Member Benefactor

      Tinnitus Since:
      2003
      I must say I have been disappointed with the overall progress of Tinnitus research in these last 10 years though, I feel I could have compressed some coal together and made diamonds on my own by now.
       
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    6. t-man
      Suicidal

      t-man Member

      Tinnitus Since:
      2009
      This won't generate new hair cells for us, will it?

      I suppose it would be like asking to grow a limp from an already healed stump.
       
    7. nills
      Barefooter

      nills Member Benefactor

      Location:
      Belgium
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      you got to hang out with these guys Hearing Health Foundation to get an answer to that :)
       
    8. Erlend
      Question it

      Erlend Member Benefactor

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      Stem Cells DO grow back limbs
       
    9. t-man
      Suicidal

      t-man Member

      Tinnitus Since:
      2009
      In crustaceans and mud puppies.

      I've never seen a lab grow an arm, yet.
       
    10. Erlend
      Question it

      Erlend Member Benefactor

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      Search youtube for stem cells ted talk
       
    11. LadyDi
      Busy

      LadyDi Member Benefactor

      Location:
      Florida, USA
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      06/2013
      Cause of Tinnitus:
      Barotrauma/airplane
      Not to be a downer: But I think tinnitus is going to be a tough research nut to crack, given it involves the brain and even something as basic as how it is triggered still isn't fully understood. Yesterday, I stumbled on this q&a from the American Tinnitus Association with two longtime researchers, talking during a conference in Belgium last year. One of them called tinnitus "more complex" than Alzheiemer's, which did NOT get my hopes up for a cure in the near future.

      Overheard at the Sixth International Tinnitus Research Initiative Conference | American Tinnitus Association
       
    12. Erlend
      Question it

      Erlend Member Benefactor

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      Seems like you're a bit pessimistic in how you [word] what he said. Interpreted?

      "However, it’s not like other diseases, like Alzheimer’s, in which you have tissue damage and neuronal degeneration. Tinnitus is much more complex, but at this point, I do not see a barrier that would prevent us from finding a cure."
       
    13. LadyDi
      Busy

      LadyDi Member Benefactor

      Location:
      Florida, USA
      Tinnitus Since:
      06/2013
      Cause of Tinnitus:
      Barotrauma/airplane
      That's a good point, Erlend. And I do think there will be a cure, or at least a very effective treatment. I just fear it will take a long time because it is a very complicated disorder, and one where the symptoms (like pain) can be difficult to measure.

      Actually, the entire article is interesting, with the researchers talking about how little research attention T received until recently, how there probably will be subgroups of patients with different types of tinnitus, etc.
       
    14. I agree that chronic tinnitus is going to be a tough nut to crack. Acute tinnitus could be treated with NMDA receptor antagonists like gancylidine, which Otonomy just purchased from the Alfred E. Mann Foundation, or Auris Medical's AM-101 to name a few. Steroids and other inflammatory inhibitors could also be used in combination. However once tinnitus is chronic, it becomes a "brain" problem as much as an inner ear problem - meaning that the brain circuits that process the tinnitus become reinforced. THIS is what makes chronic tinnitus such a complex problem. I am the CEO of a start-up in Chicago devoted to bringing an inner ear drug delivery system to market. Read our annotated page on the "Science" that explains why we are doing what we are doing at www.resonance-med.com
      Chris Heddon
      CEO
      Resonance Medical Technologies
      Chicago, IL
       
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    15. Erlend
      Question it

      Erlend Member Benefactor

      Location:
      Scandinavia
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      But why do some people's tinnitus go away after years?

      I've had tinnitus since may, 6 months now (concert). Do you think the AM101 treatment could help me in say, 2 years?

      And what if my inner ear is "fixed" and T remains, don't you think that some acoustic form of treatment could fix the brain part, if the inner ear itself is back to normal?
       
    16. erik
      Breezy

      erik Manager Staff Benefactor

      Location:
      Washington State, USA
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      04/15/2012
      Cause of Tinnitus:
      Most likely hearing loss
      I believe tinnitus may go away in some people for a number of reasons. Perhaps it was caused by a physical condition and once the condition was corrected so went the T. Or it is possible tinnitus was the result of withdrawal from long time use of a prescription that needed several months to clear. I think that in some people with mild T they eventually get used to it and perhaps get to a point where their brain doesn't hear it any longer so they think it is gone.
       
    17. Erlend
      Question it

      Erlend Member Benefactor

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      If it eventually becomes a brain problem, would listening to T sound on an iPod for 3 months cause chronic T?
       
    18. mick

      mick Member Benefactor

      Location:
      USA
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      That.s not an experiment that I want to try!
       
    19. I would say that its very likely that if you have had tinnitus for that long, it is very likely that you will be stuck with some level of tinnitus at the brain level. Since your cochlea was likely damaged at the concert, there is probably little to no input from the cochlear nerve. Therefore your brain is filling in the blanks with the last sound that it heard. Its very much like phantom limb pain - which is the very painful sensation people get after having and arm or leg cut off - the brain has a physical space for that sensation, but is getting no signal from the missing limb, so it fills in the blanks.

      It is possible that the particular nerves supplying the frequencies have lost have regressed and would need a neurotrophic factor to regrow into their original frequencies.
       
    20. Jake
      Irritated

      Jake Member

      Location:
      Lawrence, KS
      Tinnitus Since:
      07/2013
      So what you're saying is that if you have chronic tinnitus you're screwed? Because the possibility of science being able to regrow nerve/brain tissue doesn't sound like it will happen any time soon. Honestly, that doesn't sound like it will happen in our lifetime. Hate to be a downer...
       
    21. Meestijn
      Balanced

      Meestijn Member Benefactor

      Location:
      The Netherlands
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      08/2013
      For both acute and chronic?
       
    22. Meestijn
      Balanced

      Meestijn Member Benefactor

      Location:
      The Netherlands
      Tinnitus Since:
      08/2013
      So according to you noise induced T is there to stay forever?
      Thus all people with noise induced T which 'recover' after, for lets say, 2 years are in fact not recovered but the brain doesn't hear it any longer?

      At the other hand I don't care if my T in fact is still there but my brain does not hear it anymore. That equals for me silence (isn't it?)! T has been always around and for some (unknown) reason we became aware of it (unfortunatly).

      Anyway I was feeling better some days ago (hope) but that is diminishing fast due to the recent articles and feedback.

      Furthermore I hope that below also applies to me someday (fingers crossed);
      Studies have indicated that, even without any ‘treatment’, the noises disappear or at least diminish in the majority of cases, as the brain loses interest in and stops surveying the signal. This process is called ‘habituation’ and it can take several months or years.

      Or the following (from someone elso on the net, which includes also noise induced recoveries after more than 6 months);
      "I have been speaking to many people and read stories of people who got rid of their ringing in the ears . I wanted to put everything together for you.First, I must mention that I was able to find less stories of recovery from tinnitus on the internet. That's when I thought it may be forever. But then, I came across people in real life. It was astonishing to know that so many people I know had gone through this, I didn't even know. How could this be? Then I thought, if we completely got rid of the noise overnight, a very few number of us would ever come back to the board tomorrow, because you want to forget. That's why, reading the stuff on the internet is going to be always more depressing because people come here when they feel bad and lonely. In real life, stories of recovery are more common and we need to remember that.
      1-4 people I spoke to were in their early 50s. All told me that they woke up one day with ringing and it went away in one year.
      2-Our neighbor had stress related tinnitus, after she lost her mother. Her doctor put her on prozac and ginko. she was almost back to normal, but 6 months into it she started having panic attacks and went back to square one.It took her over a year and she completely got rid of the noise.
      3-A family friend took an overseas flight. When he landed his ears were ringing. He said he got really depressed and used a lot of anti depressants. He doesn't know whether it was the loud engine or the pressure change that caused it. His ears rang for 2 years and he fully recovered.
      4-I know 3 people in the army whose ears rang over a year after they left the army.
      5-I saw stories of at least 5 people on the internet whose ears rang for at least 6-7 months after a loud concert. In addition to that 2 friends of mine healed in 1- 1.5 years. I came across a story of a fellow forum member who healed in 2 years. In his post he also mentioned another friend of his who also had recovered in 2 years. All of them are noise induced tinnitus.
      6-My friend's mom had stress related T after she lost her husband. She said her ears rang for 2 years and then she fully recovered.
      7-I am not even writing stories of so many people who recovered in less than 6 months.
      So, if you come to this board as a newbie, and if you are feeling depressed, afraid and if you feel you can't go on... Stop for a moment and take a deep breath. It will get better and you will heal. We just need to accept that we are going to go through a difficult time period for a while.Cheers"
       
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    23. Erlend
      Question it

      Erlend Member Benefactor

      Location:
      Scandinavia
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      05/2013
      They are able to silence tinnitus temporarily

      Neuroscience may offer hope to millions robbed of silence by tinnitus | Tinnitus Talk Support Forum

      I dont care how it happens, as long as I my T goes away
       
    24. LadyDi
      Busy

      LadyDi Member Benefactor

      Location:
      Florida, USA
      Tinnitus Since:
      06/2013
      Cause of Tinnitus:
      Barotrauma/airplane
      I am glad to see the ResonanceCEO joining our conversations on this and other threads. Welcome, Chris.

      I am no scientist. But I would argue that tinnitus is a "brain problem" as much as an ear problem from onset, unlike other ear problems like colostomas. The neurological factors just take on more prominence than those of the inner ear as the disorder progresses. Which begs the question: Why the heck don't we see more neurologists getting involved with tinnitus patients at the very beginning, versus having us deal with ENTs who can do little while, in the meantime, the brain is rewiring itself in ways that will be hard to short-circuit later on. The medical profession needs to completely change the way this disorder is treated, in my opinion.

      I agree with Chris, that chronic T will be much harder to treat or cure than acute. Which is why a lot of the research right now is focusing on acute, as we have discussed with the AM 101 trial new recruitment. Success will be much easier to come by. With all the work in general being done on brain plasticity, I think ways to remap the neural pathways will be discovered. I don't think it will necessarily come from stem cells -- maybe instead from electrical stimulation, such as what is being used from Parkinson's. Don't know. But I don't think it will happen any time soon.

      In the meantime, hope those researchers keep looking for drug therapies or treatments that will help us chronics better manage our condition. And I think they will. There's money to be made there, too.
       
    25. jazz
      No Mood

      jazz Member Benefactor

      Location:
      US
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      8/2012
      Cause of Tinnitus:
      eardrum rupture from virus; barotrauma from ETD
      Sound Pharmaceuticals recently completed a successful Phase 2 clinical trial for its drug SPI-1005. This drug will be important for preventing tinnitus or preventing it from getting worse. One probable use would be to take it as a preventative before going to concerts or other loud events. Of course, this would be in addition to wearing hearing protection.

      Here is their press release:


      SEATTLE, Feb. 18, 2014 /PRNewswire/ -- Sound Pharmaceuticals (SPI) has submitted a scientific abstract for presentation at the American Academy of Otolaryngology-Head and Neck Surgery Annual Meeting in Orlando FL. The Phase 2 clinical trial enrolled 83 subjects with normal hearing or slight hearing loss in an iPod®music protocol that induces a slight but temporary hearing loss or threshold shift (TTS). Subjects were randomized in a double-blinded manner to either placebo or three different dosages of SPI-1005 and treated before, during, and after the music exposure. Repeated hearing tests were conducted to determine the incidence, severity and duration of the TTS over the course of one week. The data indicate that SPI-1005 treatment dramatically reduced (>50%) the incidence, severity and duration of the TTS induced by loud sound vs placebo controls. In addition, all doses of SPI-1005 were well tolerated with no observed or reported adverse events related to study drug. SPI-1005 is an oral capsule that contains ebselen, a novel molecule that mimics and induces the activity of Glutathione Peroxidase (GPx), a critical enzyme in the inner ear that protects it from damage caused by loud sounds or noise. In preclinical studies, ebselen treatment was shown to reduce the TTS and permanent threshold shift (PTS) caused by intense noise exposure or ototoxic drug exposure such as cancer chemotherapy.

      "These clinical data support the critical role of GPx activity in noise-induced hearing loss and warrant further investigation in noise exposed populations," said Jonathan Kil, MD, Chief Medical Officer and lead author of the paper. SPI is a privately held biopharmaceutical company in Seattle with a focus on developing the first drugs for the prevention and treatment of sensorineural hearing loss. Noise induced hearing loss is a significant disease and effects over 31 million in the US according to the CDC.

      "SPI is advancing its proprietary technology for hearing loss prevention and treatment through proof of concept in a clinically relevant population with growing unmet medical need," said Eric Lynch, PhD, President and co-author of the study.

      Details of the SPI-1005 clinical trial can be viewed online at www.clinicaltrials.gov, or by visiting www.soundpharma.com or by calling Eric Lynch at 206-634-2559.

      There is another article and video on this trial at the following link: http://www.king5.com/health/jean/Pi...ent-hearing-loss-shows-promise-250413601.html

      Until this drug is released, it looks like taking NAC might give you similar otoprotection. Or you could also take glutathione as a supplement.

      Here is a study on NAC to prevent NIHL: http://www.ncbi.nlm.nih.gov/pubmed/22122955

      Here is a study on glutathione in limiting NIHL: http://www.ncbi.nlm.nih.gov/pubmed/10913881

      Here is a general review of glutathione uses and dietary sources: http://www.raysahelian.com/glutathione.html
       
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    26. Nate

      Nate Member Benefactor

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    27. AlexSongitus

      AlexSongitus Member Benefactor

      Tinnitus Since:
      01/2016
      Cause of Tinnitus:
      Noise induced
      Very interesting. Would be amazing if this works.
       
    28. Carlos1

      Carlos1 Member Benefactor

      Location:
      Boston
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      Cause of Tinnitus:
      Root Canal
      @Nate hey Nate how have you managed all these years with T ? It's going on 3 years for me and it's been the toughest 3 years of my life
      Thanks a good link gives hope to all of us
       
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    29. Nate

      Nate Member Benefactor

      Location:
      MA
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      "@Nate hey Nate how have you managed all these years with T ? It's going on 3 years for me and it's been the toughest 3 years of my life
      Thanks a good link gives hope to all of us"

      I've had T since I was 19. Didn't think twice about it until I turned 30 and it got a lot louder. I still coped pretty well until on my 40th birthday it amped up again. Since then it has been a complete battle. It just amped up again the past few weeks. At first I thought it was just a spike but it has not gone down. I always protect my ears so I'm not sure what amped it up this time. At the moment I am in pretty bad shape and was hoping to find a Tinnitus specialist in my area but it seem that even at Mass Eye And Ear they don't have a specialist. They have researchers but you can not get an appointment with any of them.

      I would kill to find someone in my boat that has dealt with the same loudness and as long as I have or longer just to pick their brain.

      How about you, what do you do to survive?
       
    30. Nate

      Nate Member Benefactor

      Location:
      MA
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      also, could someone tell me how to quote someone in a post? Thanks in advance
       

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