Stock Watch: Unity Biotechnology, $UBX, due for clinical data release. Senescence and diabetic macular edema + PUFA-link

[IROM]

[Disclosure: Not a financial advisor, this is not financial advice. I hold 250 shares and still DCA'ing.]

Unity Biotechnology, which failed on products combatting arthritis and joint problems has retooled to fight ocular disease; specifically Diabetic macular edema. Especially in treatment related to Diabetes (which is directly linked to elevated FFAs), I think that their anti-senescent compounds are right on target. Ray has talked about the many IRREVERSIBLE effects of PUFAs on cells. Georgi has discussed the causal link between PUFA metabolites and cellular senescence (shown below.) UBX seems to be onto a process by which these PUFA-laden cells can be removed. UBX is due to end their first trials in October 2021 and the data will be compiled by the end of year. UBX has fired their employees in the previous arthritis/joint division and is doing massive hiring for ophthalmology.

While UBX may have been stupid regarding Arthritis/Joint issues, I think the focus on diabetes-related eye issues targeting senescence and thereby also targeting elevated FFA induced damage is in the Peatarian sphere of interest. The lack of dangerous side-effects puts these drugs into the Peatarian sphere. This is one thing Peat doesn't really have a solution for and I think demonstrates a Noospheric revolution in the pharmaceutical industry.

Information on drug pathway:

Bcl-xL - Wikipedia

en.wikipedia.org

Unity Biotech recent Press Release:

UNITY Biotechnology Announces Positive 12-Week Data from Phase 1 Clinical Trial of UBX1325 in Advanced Vascular Eye Disease | Unity Biotechnology

Evidence of improvement in vision and retinal structure in patients with DME and AMD sustained through 12 weeks Sustained responses following single treatment with UBX1325 support durability of senolytic therapeutic approach; data builds on previously reported results at 8 weeks Study remains on

ir.unitybiotechnology.com

“We are excited by the trajectory of the data showing both a rapid response and sustained improvements in vision and retinal structure in most patients through 12 weeks following a single injection of UBX1325,” said Anirvan Ghosh, Ph.D., chief executive officer of UNITY. “The consistency of response at 8 and 12 weeks suggests that the functional gains seen to date may be sustained beyond 12 weeks. These data further support our Phase 2a Proof of Concept study in patients with DME, which is already underway, and we anticipate the 12-week safety and efficacy data from that study in the first half 2022.”

Georgi has discussed the PUFA-Senescent connection here:

Striking Accumulation Of PUFA In Aged Cells

Peat has written many times about the changes that occur in "aged" cells. Those changes are virtually indistinguishable from the ones that occur in "sick" cells and are characterized by reduced mitochondrial number/size and a shift in lipid composition away from saturated and towards unsaturated...

raypeatforum.com

"...The study found that during cellular senescence, the accumulation of triacylglycerols corresponded with a significant increase in the levels of genes involved in responding to oxidative stress...All had a remarkably similar structure, featuring long chains of fatty acids, including at least one polyunsaturated fatty acyl (PUFA) chain."

Thus, one would expect that aging (and disease) to be associated with a shift in cellular lipid composition in general (and CL composition in particular) towards PUFA. However, up until now evidence for age-related changes in cell lipid composition in favor of PUFA has been sparse to non-existent. The study below changes the status quo by demonstrating that senescence is characterized by a striking accumulation of PUFA inside cells. In fact, of the 19 types of triacylglycerols present in relative abundance in aged cells compared to adult ones, every single one of those glycerol types contained at least one PUFA member. The study does not go as far as to say that this accumulation is what drives aging because the study only looked at association, not causality. However, the fact that the level of PUFA accumulation was age-dependent implies causality and the knowledge about the effects of PUFA on CL function seals the deal, at least for me. The conclusion of the study was that lipids are far from passive when it comes to health and aging and they may regulate the very process of aging itself. I will go a step further and state that PUFA accumulation is the major cause of cell aging and reversing that accumulation likely restores a cell's biological age back to youthfulness.

"...Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence. Based on the transcriptome analysis, we propose that the activation of CD36-mediated fatty acid uptake and diversion to glycerolipid biosynthesis could be responsible for the accumulation of triacylglycerols during replicative senescence."

 

[IROM]

For TD;LR Diabetes causes apoptosis and cellular senescence (and we know part of this process is part of elevated FFAs and PUFA metabolites damaging cells) however, a protein called BCL-lx stops apoptosis. Current BCL-lx inhibitors on the market cause apoptosis in healthy and unhealthy cells. The UBX drug targets only senescent PUFA-damaged cells and triggers apoptosis while leaving healthy cells untouched.

BCL-lx stops the release of Cytochrome Oxidase. PUFA also stops the release of Cytochrome Oxidase. Cytochrome Oxidase attacks ROS-over-producing cells but is inhibited by PUFA. UBX1235 can, in theory, restore proper Cytochrome Oxidase Function and reverse PUFA damage.

From V P Skulachev:

Cytochrome c release can be initiated by the pro-apoptotic protein Bax. This process is blocked by the anti-apoptotic proteins Bcl-2 and Bcl-xL. The role of cytochrome c in apoptosis may be understood within the framework of the concept assuming that the evolutionary primary function of apoptosis was to purify tissues from ROS-overproducing cells. In this context, the pro-apoptosis activity of cytochrome c might represent one of the anti-oxidant functions inherent in this cytochrome.

From Ray:

“A crucial enzyme in the mitochondrion is cytochrome oxidase, which reacts directly with oxygen, completing (or beginning) the process of chemical respiration. It is this enzyme (which is most sensitive to cyanide) which appears to be a “choke point” for energy production in various situations. Learning how to preserve and promote the activity of this enzyme is an important issue for everything having to do with biological energy…Kunkel and Williams (J. Biol. Chem., 1951) found that the very high respiratory rate of animals fed a diet lacking polyunsaturated fats was caused primarily by a great increase in the activity of cytochrome oxidase, and that adding an “essential fatty acid” strongly inhibited this enzyme’s activity.”

 

[Don]

Interesting, thanks for the info.

 

[Lollipop2]

I agree. Interesting. Thank you for taking the time share.

 

[steel_reserve]

Are you the guy who called in to the Alex Jones show about ubx?

 

[IROM]

Are you the guy who called in to the Alex Jones show about ubx?

Lol I wish. I'd have a few words to say to AJ. What exactly did the guy say?

The Peter Thiel connection to that milieau might be the reason why someone decided to share with Alex. They are all part of the "Intellectual Dark Web" around Joe Rogain and his libertarian stoner society.

 

[steel_reserve]

I can't remember why he brought it up but it perked my ears because I couldn't believe I heard the word senescence on infowars AND Alex Jones knew what it was

 

[IROM]

Alex Jones wants to live for ever that's why he wants to eat his neighbors and their adrenal glands lol.

View: https://www.youtube.com/watch?v=rfZcKCIcug8

 

[IROM]

UPDATE: UBX has success with BCL-xl inhibitors for FFA/Diabetes induced senescence. So it is now possible to remove tissue-damaging lipid metabolites which cause senescence by activating cytochrome oxidase and allowing the cells to naturally be destroyed and replaced.

UNITY Biotechnology Announces Improvement in Visual Acuity Sustained Through 24 Weeks Following Single Dose of UBX1325 in Phase 1 Study of Patients with Advanced Vascular Eye Disease | Unity Biotechnology

Patients with diabetic macular edema in higher dose cohorts showed a mean BCVA gain of approximately 10 ETDRS letters sustained through 24 weeks after a single intravitreal injection Patients with wet age-related macular degeneration showed improvement in visual acuity through 12 weeks supporting

ir.unitybiotechnology.com

• • Across all DME patients enrolled (n=8), there was an improvement in visual acuity in 6 of 8 patients at 12 weeks, and in 5 of 8 patients at 24 weeks
• • In the higher dose cohorts (5, 10 mcg), patients had a mean improvement of 9.5 ETDRS letters from baseline at 24 weeks
• • Amongst all DME patients, 62.5% gained 5 or more letters at 24 weeks, and 50% gained 10 or more letters also at 24 weeks
• • In the majority of patients with DME, CST remained stable through 24 weeks

“A 10 letter gain in DME patients, maintained through six months, is an impressive outcome, and is particularly noteworthy considering that it was achieved with a single injection,” said Arshad Khanani, M.D., M.A., managing partner of Sierra Eye Associates.​

 

[Don]

UPDATE: UBX has success with BCL-xl inhibitors for FFA/Diabetes induced senescence. So it is now possible to remove tissue-damaging lipid metabolites which cause senescence by activating cytochrome oxidase and allowing the cells to naturally be destroyed and replaced.

UNITY Biotechnology Announces Improvement in Visual Acuity Sustained Through 24 Weeks Following Single Dose of UBX1325 in Phase 1 Study of Patients with Advanced Vascular Eye Disease | Unity Biotechnology

Patients with diabetic macular edema in higher dose cohorts showed a mean BCVA gain of approximately 10 ETDRS letters sustained through 24 weeks after a single intravitreal injection Patients with wet age-related macular degeneration showed improvement in visual acuity through 12 weeks supporting

ir.unitybiotechnology.com

price is up in the after hour market

 

[IROM]

price is up in the after hour market

Yep buying more tomorrow. Should have about a thousand shares and that is a good enough flip for me if it hits 10.00