Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus

#1,981
Silvio Sabo said:
Size wouldn't matter since your are measuring mg/kg. A dose of 1 600 mg in humans would correspond to around 4,5 mg in mice (if you count that an average human is around 70 kg and an average mouse is around 200 g).

Also children are more sensitive to drugs in general so I think it would be safer to give higher doses to adults.

But I think that if there are differences in doses it's not due to differences in body mass but differences in metabolism and the relative size of the brain. It might be so that we have to give higher doses to humans since our brains are bigger then in mice compared to our body mass (the brain makes up about 2-3% of the body mass in the average human). But then again mice have a higher metabolism rate then humans so they might tolerate higher doses. The only way to find out is to try I guess. :)
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Thanks for the information. Anyway,Keppra bypasses other organs, so you don't have the risk of liver damage. It's used in children. So keppra isn't dangerous and it works on the KV3 channels, so I'm wondering if Autifony's drug will be the same?
 
#1,983
Xorthian said:
@Danny Boy but keppra doesnt do anything to T right.
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Well, Keppra may not be potent enough. Viking said say it lowered his tinnitus by 30%. I can't comment as I'm using both. But hey, it could work, as it does work on the same channels. Anyway, it seems safe enough to try.
 
#1,984
Danny Boy said:
Well, Keppra may not be potent enough. Viking said say it lowered his tinnitus by 30%. I can't comment as I'm using both. But hey, it could work, as it does work on the same channels. Anyway, it seems safe enough to try.
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Sooooo can quote from somewhere what does keppra target and what does aut063 target?
I'm quite curious actually.
 
#1,985
To be honest im starting to get lost with what aut063, trobalt, keppra, scifulor and that 10x more potent keppra in trials are doing on what. It would be great if someone could compile chart about basic information on each of them since it starts to get really confusing really fast...
 
#1,986
Xorthian said:
Sooooo can quote from somewhere what does keppra target and what does aut063 target?
I'm quite curious actually.
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http://www.ncbi.nlm.nih.gov/pubmed/20065495

Experimental and simulation studies on the mechanisms of levetiracetam-mediated inhibition of delayed-rectifier potassium current (KV3.1): contribution to the firing of action potentials.
Huang CW1, Tsai JJ, Huang CC, Wu SN.
Author information

Abstract
Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with established antiepileptic efficacy in generalized epilepsy and partial epilepsy. However, its effects on ion currents and membrane potential remain largely unclear. We investigated the effect of LEV on differentiated NG108-15 neurons. In these cells treated with dibutyryl cyclic AMP, the expression level of the K(V)3.1 mRNA was elevated. With the aid of patch clamp technology, we found that LEV could suppress the amplitude of delayed rectifier K(+) current (I(K(DR))) in a concentration-dependent manner with an IC(50) value of 37 microM. LEV (30 microM) shifted the steady-state activation of I(K(DR)) to a more positive potential by 10 mV, without shifting the steady-state inactivation of I(K(DR)). Neither Na(+), nor erg (ether-a-go-go-related)-mediated K(+) and ATP-sensitive K(+) currents were affected by LEV (100 microM). LEV increased the duration of action potentials in current clamp configuration. Simulation studies in a modified Hodgkin-Huxley neuron and network unraveled that the reduction of slowly inactivating I(K(DR)) resulted in membrane depolarization accompanied by termination of the firing of action potentials in a stochastic manner. Therefore, the inhibitory effects on slowly inactivating I(K(DR)) (K(V)3.1-encoded current) may constitute one of the underlying mechanisms through which LEV affect neuronal activity in vivo.
 
#1,991
Danny Boy said:
Thanks for the information. Anyway,Keppra bypasses other organs, so you don't have the risk of liver damage. It's used in children. So keppra isn't dangerous and it works on the KV3 channels, so I'm wondering if Autifony's drug will be the same?
Click to expand...

From what I've read about Keppra it's not known how it really works. But what is known is that when it's used in combination with other drugs for epilepsy it makes them work better. It's sort of a support drug that is meant to be taken together with other anti epileptic drugs.
 
#1,992
Silvio Sabo said:
From what I've read about Keppra it's not known how it really works. But what is known is that when it's used in combination with other drugs for epilepsy it makes them work better. It's sort of a support drug that is meant to be taken together with other anti epileptic drugs.
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Trobalt is the same in that it's used in addition to other epileptic drugs.
 
#1,993
Danny Boy said:
Trobalt is the same in that it's used in addition to other epileptic drugs.
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Yes but with Trobalt it's known that it works on Kv channels and by which mechanism wheras with Keppra it's a bit unclear. It is stated that it binds to a synaptic vesicle protein, inhibits presynaptic calcium channels and reduces neurotransmitter release. However the mechanism is unknown. Also it's unclear as to what type of ion channels it works on and how promiscuous it is in it's targeting of ion channels.

When it comes to the treatment of epilepsy, as I've understood it, it's common to prescribe a mix of drugs. I also believe that we might have to adopt the same strategy in tinnitus once there are drugs available. Therefore I think it's not a bad thing that there are multiple drugs/treatments in the pipeline and being tested at the moment.
 
#1,994
Silvio Sabo said:
Yes but with Trobalt it's known that it works on Kv channels and by which mechanism wheras with Keppra it's a bit unclear. It is stated that it binds to a synaptic vesicle protein, inhibits presynaptic calcium channels and reduces neurotransmitter release. However the mechanism is unknown. Also it's unclear as to what type of ion channels it works on and how promiscuous it is in it's targeting of ion channels.

When it comes to the treatment of epilepsy, as I've understood it, it's common to prescribe a mix of drugs. I also believe that we might have to adopt the same strategy in tinnitus once there are drugs available. Therefore I think it's not a bad thing that there are multiple drugs/treatments in the pipeline and being tested at the moment.
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Only thing is waiting for these drugs to be released. For now, we have keppra and trobalt and we have to make do with them.
 
#1,995
Danny Boy said:
It did. I just swear I read somewhere about the 30%.
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Yes, you are right. I don´t remember who, but he had tried many different variations of drugs, and stated this about Keppra: "Keppra (Levetiracetam) 2000mg + 1mg Clonazepam 20 max 30% stable on tinnitus relief. No spike. No side effect (very good) ... the mystery of the disappearance of hyperacusis."

I know, cause I copy n pasted it to an own document for future reference in trying to convince a doctor/nevrophysician to let me try it out.
 
#1,996
grate_biff said:
Yes., you are right. I don´t remember who, but he had tried many different variations of drugs, and stated this about Keppra: "Keppra (Levetiracetam) 2000mg + 1mg Clonazepam 20 max 30% stable on tinnitus relief. No spike. No side effect (very good) ... the mystery of the disappearance of hyperacusis."

I know, cause I copy n pasted it to an own document for future reference in trying to convince a doctor/nevrophysician to let me try it out.
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Yeah, I thought I read that somewhere! Thanks for backing me up!
 
#2,002
sergerold said:
People need to keep on topic. 99% of the stuff being posted is not relevant to aut00063.
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Mmmmeehh....
See, there is very little to no new news on aut00063. So, this thread has become the chat line for current things in general as well as any news regarding au00063. The members have self-organized this way which generally means it makes the most sense. It has the most activity by far so I wouldn't worry about trying to manage the content flow.
 
#2,005
a guy on another tinnitus site mentioned that he was going to ENT tomm. and he was going to participate in the quiet study... he lives in uk... hoping he will come on here and share his experience as well..
 

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