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First-in-human trial of senolytic drugs encouraging

senolytic d & q

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#1 VP.

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Posted 07 January 2019 - 07:30 PM


UT Health San Antonio researchers, collaborating with the Mayo Clinic and the Wake Forest School of Medicine, are the first to publish results on the treatment of a deadly age-related disease in human patients with drugs called senolytics. The findings were posted Jan. 4 by the journal EBioMedicine,which is published by The Lancet.

Each participant received two senolytic drugs, dasatinib and quercetin (DQ), taken by mouth for three consecutive days each week for three consecutive weeks (nine doses total). All patients were able to comply with this regimen without any discontinuation of the study drugs.

Results

The most consistent improvements following senolytic therapy were observed in participants' mobility. The six-minute walk test, timed sitting-to-standing repetitions and other measures were significantly improved after completion of the treatment. The majority of patients exhibited mobility gains of greater than 5 percent. Other physical function markers, including grip strength and pulmonary function testing, did not change.

"No drug therapies, including the available anti-fibrotic drugs, have ever shown to stabilize, let alone improve, an IPF patient's six-minute walk distance," Dr. Nambiar said. "But in this pilot study of DQ, participants' six-minute walk distance improved an average of 21.5 meters.

https://www.scienced...90107112944.htm


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#2 VP.

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Posted 07 January 2019 - 07:35 PM

A two-center, open-label study of intermittent DQ (D:100 mg/day, Q:1250 mg/day, three-days/week over three-weeks) was conducted in participants with IPF (n = 14) to evaluate feasibility of implementing a senolytic intervention. 

   Not very impressive but it's well tolerated and it's a start. 


Edited by VP., 07 January 2019 - 07:41 PM.

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#3 Daniel Cooper

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Posted 07 January 2019 - 09:52 PM

I wouldn't characterize those results as "not very impressive".  People generally never improve with pulmonary fibrosis.

 

Good find.  Thanks.

 

 

 

 

 


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#4 Krell

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Posted 08 January 2019 - 01:10 AM

"Other physical function markers, including grip strength and pulmonary function testing, did not change." But they were able to walk further!!

 

What exactly is "pulmonary function testing"  and what other factors would allow someone to walk further in 6 minutes if their pulmonary function did not change?

 

According to Wikipedia

 

"Pulmonary function testing is a complete evaluation of the respiratory system including patient history, physical examinations, chest x-ray examinations, arterial blood gas analysis, and tests of pulmonary function. The primary purpose of pulmonary function testing is to identify the severity of pulmonary impairment."

 

What about increased heart function?  Would that not show up on "pulmonary function testing" and allow for longer distance walked?

 

I am no expert, so I am looking for more expert opinion.

 

Of course, this could just be a placebo effect, since the sciencedaily.com article does not say anything about placebo controls.

 

Or perhaps it could be some increase in leg function that was not strength, assuming that the failure to increase grip strength rules out increased leg strength.

 

My main interest here is trying to figure out what to measure before and after taking senolitics to determine their efficacy.  Is this study telling us something

related to this?

 

Interesting.


Edited by Krell, 08 January 2019 - 01:40 AM.


#5 albedo

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Posted 08 January 2019 - 08:02 AM

It is a very good find. Thank you. It is a pilot study, hence lacking the placebo control arm as the authors indicate in the discussion. They also do refer to biomarkers one can measure before and after DQ treatment incl. SASP circulatory features and

 

"...Our previous work demonstrated increased senescent cell abundance in lungs of subjectswith IPF, including upregulation of p16INK4A (CDKN2A),which correlatedwith disease severity [5]. Additionally, p16INK4A+ fibroblasts and epithelial cells with telomere-associated DNA damage foci (TAFs), another marker of cellular senescence, accumulated in fibrotic regions of honeycomb lung in patients with IPF, together with increased expression of SASP components (including the matrix remodeling proteins and pro-inflammatory factors that were tested in the blood of subjects in the present study) [5]..."

 

I think the work point to the reduction of inflammatory biomarkers and others also touched in our thread for biological age, e.g. here and related posts.



#6 albedo

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Posted 08 January 2019 - 08:13 AM

Pulmonary function is typically included in panel of biomarkers of aging integrating both functional (e.g. pulmonary FEV1 as in the study) and others such as inflammatory/immune, anthropometric etc ... (see also on the biological age thread, here)

 



#7 albedo

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Posted 08 January 2019 - 01:41 PM

...

 

My main interest here is trying to figure out what to measure before and after taking senolitics to determine their efficacy.  Is this study telling us something

related to this?

 

Interesting.

 

Also, in case you overlooked it, you might be also refer to this blog post:

 

https://www.fightagi...ts-and-measures



#8 Daniel Cooper

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Posted 08 January 2019 - 09:45 PM

BTW - we really need a senolytics sub forum.  We've got stuff on this topic spread all over.


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#9 izan82

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Posted 11 January 2019 - 09:05 PM

BTW - we really need a senolytics sub forum.  We've got stuff on this topic spread all over.

 

 

I agree!

 

 

 



#10 Rick Flair

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Posted 13 January 2019 - 05:28 PM

Have you guys and gals looked at this interview? It appears that using D&Q may be good for the short time, but bad in the long run. https://www.noozhawk...faloon_20181108

 

 

Here is the interview that Bill Faloon refers to.  https://www.leafscie...rived-part-two/

 

Something to think about


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#11 smithx

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Posted 14 January 2019 - 06:48 AM

Have you guys and gals looked at this interview? It appears that using D&Q may be good for the short time, but bad in the long run. https://www.noozhawk...faloon_20181108

 

Here is the interview that Bill Faloon refers to.  https://www.leafscie...rived-part-two/

 

Something to think about

 

The first interview you linked was really interesting, thanks.

 

In that interview, the 2nd one you linked seems to be addressed here:

 

 


TH: If senolytics are used many times over the course of one’s life at what point will we need the complementary therapies you suggest, like stem cells, to replace senescent cells that are removed with senolytics?

 

BF: No one knows this yet, but we have comprehensive strategies to deal with this potential eventuality, such as identifying affordable sources of effective stem cell replacements. And please understand that we are not removing that many senescent cells. I’ve seen microscopic photos of senescent cells in tissues and there are not that many of them. What the Mayo Clinic scientists discovered and published in August (Nature Medicine, reference provided above) is that one senescent cell among 7,000 to 15,000 healthy cells initiate pathologic changes characteristic of degenerative aging. If you look at these photos, there are not a lot of senescent cells to remove.

 


Edited by smithx, 14 January 2019 - 06:49 AM.

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#12 Rick Flair

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Posted 14 January 2019 - 11:46 AM

I hear Faloon saying something like this.
1. Who knows
2. We have no strategy in place to deal with it.
3. You may need Stem Cell blah blah blah. The Stem Cell thing may be expensive.
4. I am in business to make money and am not an expert in the medical field. I have looked at photos and rendered an opinion.
5. These Stem Cell treatments might not fix the problems that D&Q created.

On a personal note. I like Faloon and am glad he is out there doing what he does.

Thanks
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