Ichor Therapeutics Announces Lysoclear SENS Rejuvenation Therapy and Series A Fundraising for Further Development

As regular readers will be aware, the company Ichor Therapeutics has for the past year or so been actively developing one of the results of the LysoSENS medical bioremediation program in order to produce a viable therapy. Today there is news of progress, and the work is moving on to the next stage of development and funding. This line of research sought to find bacterial enzymes that can degrade forms of metabolic waste that our cellular biochemistry struggles with, particular the constituents of lipofuscin. Lipofuscin compounds, varying in type from tissue to tissue, accumulate in the cellular recycling system known as the lysosome. That is where cellular waste ends up, but what happens when it cannot be effectively broken down? The answer is that lysosomal activity starts to fail, and cells fall into a form of garbage catastrophe as a result, a process of growing damage and functional decline that, as it happens across all cells in a tissue, contributes to degenerative aging. In most cases the process of cause and effect that leads from lipofusin to age-related disease isn't clearly and completely mapped, but for some conditions the contribution of lipofuscin compounds is quite direct, and so better known. Ichor is focused on the metabolic waste compound A2E as it pertains to macular degeneration, a common age-related condition of progressive blindness. Here, researchers have very good evidence for the harms caused fairly directly via A2E accumulation.

The best thing to do with unwanted metabolic waste is to find a way to safely break it down so that its components can be recycled appropriately. Given that this waste is a cause of aging, successful removal will be a narrow, targeted form of rejuvenation. The path chosen by the SENS Research Foundation in their LysoSENS program was based on the observation that graveyards and similar locations do not appear to be saturated with human metabolic waste. Therefore soil bacteria must be consuming this material. Given the enormous number and variety of bacterial species, somewhere in there is very likely to be found one or more molecules that can form the basis for a drug that can break down metabolic waste compounds without harming cells. Finding such a compound starts with culturing bacteria in order to find those that can thrive on a diet of human lipofuscin, and after some years of work, a range of candidates for various forms of metabolic waste were indeed discovered, including one for A2E. Given a single suitable molecule, it is then possible to build others in the same class, and search for those that are most effective and least likely to harm cells and tissues via unwanted side-effects.

The lipofuscin constituent A2E is peculiar to the very energetic metabolism of retinal cells, so Ichor Therapeutic's work is the production of a very narrowly focused rejuvenation therapy indeed, applicable only to this tissue in the eye. It is nonetheless a rejuvenation therapy and one of a growing number of examples of the work of the SENS Research Foundation moving to the clinic. This may be just one tissue, but there are a great many patients suffering with macular degeneration, no currently effective treatment for the dry form of the condition, and consequently signs of progress in the field tend to attract attention from Big Pharma. The work of the SENS Research Foundation and Ichor Therapeutics here is another article of proof to show that the right way to proceed towards the effective treatment of aging and age-related disease is to repair and reverse the fundamental differences between old and young tissue - such as the accumulation of metabolic waste that our biochemistry cannot effectively break down.

Considering all of this, I'm pleased to note, both as an investor in the company and as someone who wants to see the field of rejuvenation research grow enormously, that the work at Ichor Therapeutics has continued to produce excellent results as it moved into animal studies. The company has accordingly announced the Lysoclear product line, and is now seeking series A funding for further development leading towards a clinical therapy to turn back the progression of macular degeneration by removing one of the root causes of the condition, the A2E accumulation. Everyone who, back in the day, helped out with the early LysoSENS research in one way or another, as researchers, advocates, and donors to the Methuselah Foundation and SENS Research Foundation, should be feeling proud and vindicated today.

Lysoclear

Lysoclear is an enzyme therapy being developed for age-related macular degeneration (AMD) and Stargardt's macular degeneration. Age-related macular degeneration (AMD) is the leading cause of vision loss among people over the age of 50, affecting 20 million Americans. Stargardt's macular degeneration is an inherited conditions that robs children of their sight. Lysoclear shows promise as a highly targeted treatment for both conditions. Lysoclear has been extensively studied in buffer systems, cell culture models, and in vivo, and findings suggest that Lysoclear is safe and effecting at destroying toxic vitamin A aggregates (A2E) that may cause these diseases. Lysoclear is safe and effective at breaking down toxic A2E, removing up to 10% with each dose. Lysoclear selectively localizes to the lysosomes of retinal pigmented epithelial (RPE) cells where A2E accumulates, and destroys it.

Age-related macular degeneration (AMD) and Stargardt's macular degeneration (SMD) are thought to arise from the gradual loss of RPE cells of the macula, the area of the eye responsible for central vision. The accumulation of toxic vitamin A aggregates, including the bis-retinoid A2E, have been implicated in these diseases. Recent research suggests that A2E is capable of binding native lysosomal enzymes, inhibiting their function. As A2E accumulation reaches a critical threshold, lysosomal impairment leads to the accumulation of intracellular lipofuscin, extracellular drusen deposition, and eventually RPE cell death. Lysoclear is a recombinant enzyme product under development by Ichor Therapeutics that is able to selectively localize to the lysosomes of RPE cells where A2E accumulates, and destroy it.

Ichor Therapeutics announces series A offering for LYSOCLEAR to move first SENS therapy into the clinic

Today, Ichor Therapeutics, a biotechnology company that focuses on developing drugs for age-related diseases, announced a series A offering to bring its Lysoclear product for age-related macular degeneration (AMD) and Stargardt's macular degeneration (SMD) through Phase I clinical trials. This product would be the first clinical candidate based on the SENS paradigm, pioneered by biomedical gerontologist Dr. Aubrey de Grey. AMD is the leading cause of vision loss among people over the age of 50. The underlying pathology of AMD is thought to be caused by the death of retinal pigmented epithelial (RPE) cells, which photoreceptors in the macula rely upon to survive. RPE cells assist photoreceptors in various metabolic roles, including the recycling of vitamin A, an essential component of the visual cycle. However, this is a leaky process, and trace by-products are formed that accumulate in the lysosomes of RPE cells. The most well studied of these by-products is A2E, a toxic compound which may play a causative role in AMD and SMD.

Although A2E accumulates gradually over the lifespan, it is generally not until later age that A2E reaches a threshold necessary to promote toxicity. At high concentrations, A2E promotes the formation of intracellular junk termed lipofuscin. RPE cells attempt to handle this accumulation by shuttling the junk out in the form of extracellular drusen. Eventually, the RPE cells choke on the garbage, and cell death accompanies complement activation, inflammation, and hypoxia. Multiple companies have developed drugs that successfully reduce the rate of A2E formation, but such interventions may be too late for symptomatic patients, who have already had the cascade kicked off.

In 2014, Ichor Therapeutics completed a material and technology transfer agreement for rights to concepts and research pioneered by SENS Research Foundation. In 2017 Ichor announced Lysoclear, a recombinant enzyme product that selectively localizes to the lysosomes of RPE cells where A2E accumulates, and destroys it. Ongoing studies suggest that LYSOCLEAR is safe and effective at targeting A2E, eliminating up to 10% with each dose. Ichor has opened a Series A funding round to support pre-clinical Investigational New Drug (IND) enabling studies and phase I human clinical trials for AMD and SMD.

Comments

Very good news :) I hope phase I goes well.

Posted by: Antonio at February 15th, 2017 3:08 PM

Very good news but is there any more info on what molecules from which bacterial strain have been used. Are there any papers?

Posted by: K. at February 15th, 2017 5:03 PM

"the work at Ichor Therapeutics has continued to produce excellent results as it moved into animal studies" That is not in their press materials, so I don't know if you accidentally spilled the beans there Reason, although it probably doesn't matter as they'd be telling investors that anyway?

It is very good to hear that Ichor have gotten over the next hurdle of producing an in vivo result a few times. I was imagining that toxicity could still be a big risk all throughout testing.

Good luck to everyone involved.

Posted by: Jim at February 15th, 2017 7:59 PM

Can anyone describe the presumed effects of taking some future generalised Lipofuscin disruptor ? Would middle-aged or old people taking such a drug feel different, look different, enjoy lower risk of suffering from maturity-onset diseases (cancer, CHD, stroke, diabetes), have more strength or endurance, think better or experience some other benefit ?

What would happen to the Lipofuscin fragments ?

And as for LYSOCLEAR itself, does it concentrate specifically in the eye, or will it have any collateral pervasive whole-body effects ?

Posted by: David Chambers at February 16th, 2017 7:47 AM

@David Chambers: In the general category of things that end up stuck in the lysosome, it is known that there is another compound, 7-ketocholesterol, that contributes to atherosclerosis development.

https://www.fightaging.org/archives/2016/06/7-ketocholesterol-accumulation-speeds-calcification-of-blood-vessels/

Separately, one research group restored youthful levels of liver function in mice by improving lysosomal function without removing lysosomal junk - you'd expect a similar outcome from getting rid of that junk.

https://www.fightaging.org/archives/2008/08/a-little-more-on-preventing-declining-liver-function-with-age/

For the most part, however, specific correlations between health, function, and lysosomal garbage are only going to be discovered by removing this stuff and observing the outcome.

Fragments of broken down compounds will be recycled by the cell.

Lysoclear will probably be injected into the eye. It could be taken up by any cell, but since A2E doesn't appear to be significant elsewhere in the body, there would be little point.

Posted by: Reason at February 16th, 2017 8:02 AM

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