Also may be useful for other collagen and stem cell therapy applications
Irvine, CA and Salt Lake City, UT - May 22nd, 2020 - Leonhardt's Launchpads innovation and startup launch accelerator, focused on bioelectric and biologics based organ regeneration and healing, announced today the discovery, development and patent filing for bioelectric controlled expression of the COL17A1 protein (also known as collagen XVII).
Last year a separate independent group in Japan published on the beneficial effects of COL17A1 in skin regeneration in Nature https://www.nature.com/articles/s41586-019-1085-7 that was widely covered in the media - https://www.thejakartapost.com/life/2019/04/04/forever-young-study-uncovers-protein-that-keeps-skin-youthful.html This method required the application of chemicals to active the COL17A1.
Stem cells underlie tissue homeostasis, but their dynamics during ageing—and the relevance of these dynamics to organ ageing—remain unknown. Here we report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modeling show that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing. Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention.
That same team also published results in Science https://pubmed.ncbi.nlm.nih.gov/26912707/ demonstrating the role of chemically induced COL17A1 in preventing hair thinning.
Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by COL17A1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.
This Leonhardt patent filing is the first to describe a device and method of stimulating a potent release of COL17A1 from a person's own tissues via natural level precise bioelectric signaling sequences. For many this may be a preferred alternative choice to getting COL17A1 originating from another person or synthesized in a lab as a chemical mix or a drug for injection or topical administration.
Howard J. Leonhardt, Executive Chairman and CEO, stated: "We believe that this pioneering discovery and patent filing adds greatly to our IP platform for organ regeneration and healing especially for skin and hair regeneration. Published studies have demonstrated an important role for COL17A1 in enhancing skin and hair regeneration as well as the potential to be useful for other stem cell therapy and collagen based applications. Our team will carefully now study further this candidate therapeutic option in a methodical manner and look forward to reporting results to you soon".
"I am very proud of our lab team that worked long hours running hundreds of experiments over many months to get to this breakthrough COL17A1 controlled protein expression discovery" stated Sejal Chaudhari, R&D Program Manager at Leonhardt's Launchpads Utah, Inc. "The discovery was validated by repeating the bioelectric stimulation experiments multiple times to verify consistent ability to produce COL17A1 reliably on demand" she further stated.
March of 2019 the same Leonhardt team announced filing of a patent for bioelectric expression of klotho another protein known to have many anti-aging benefits from numerous studies - https://www.biospace.com/article/leonhardt-s-launchpads-announces-filing-of-patent-for-bioelectric-stimulation-controlled-klotho-expression-powerful-anti-aging-and-regeneration-promoting-protein-/. Earlier this month the same team received a full issuance of a U.S. patent focused on bioelectric controlled expressions of SDF1 and PDGF for stem cell homing combined with repeated deliveries of a regeneration promoting stem cell and/or biologics mixed composition intended for organ regeneration and healing. This newly patented invention is designed to be applied across a wide variety of applications including internal and external organs - https://patents.justia.com/patent/10646644
The same Leonhardt team also previously announced a patent pending bioelectric signaling sequence to increase expression of tropoelastin, a precursor for the production of elastin, for improving elasticity of tissues including skin, bladder, arteries and the heart. This new COL17A1 patent filing complements well the previous regenerative protein expression technologies developed and tested by the team.
SkinStim www.skin-stim.com, Vascustim www.vascustim.com and HairCell www.haircellstim.com will be the first startups in the accelerator portfolio that will begin applying the COL17A1 into their studies forward.
About Leonhardt's Launchpads:
Leonhardt's Launchpads is the innovation and startup launch accelerator arm of Leonhardt Ventures LLC (founded in 1982 as HJ Leonhardt & Co.) with R&D labs in California and Utah and branch locations in Minneapolis, Santa Rosa, Porto Allegre, Brazil, Australia and Pittsburgh. The 2020 portfolio class https://leonhardtventures.com/development-pipeline/ includes 30 startups/innovations in the areas of (1) Heart & Cardiovascular, (2) Brain, (3), Cosmetic, Personal Care & Reproductive Health, (4) Major Organ Regeneration and (5) Cancer. The accelerator business model is to accelerate each organ specific innovation & corresponding startup through first in human clinical study results and then seek a strategic partner to advance the rest of the product development through commercialization. The company has 17 products at clinical stage of development and 13 at pre-clinical stage. The accelerator has over 600 issued, pending, optioned or licensed patent claims https://patents.justia.com/inventor/howard-j-leonhardt for organ regeneration and recovery technologies mostly built around bioelectric and biologics based therapies. Over 800 patients have been enrolled in clinical studies across all products following our filed or issued patent claims via a network of independent researchers. The primary bioelectric stimulator used in most these studies is produced in Anaheim, California and has FDA 510K market clearance for improving blood circulation, pain relief and other selected indications of use - https://www.accessdata.fda.gov/cdrh_docs/pdf11/K113017.pdf. The Leonhardt team is gathering additional well controlled clinical data to support new filings with the FDA intended to expand the labelling indications of use.
2020 Annual Report link >https://leonhardtventures.com/wp-content/uploads/2020/04/4_23_2020.pdf
Note full legal names are Cal-X Stars Business Accelerator, Inc. DBA Leonhardt's Launchpads, Leonhardt's Launchpads Utah, Inc. and Leonhardt Vineyards LLC DBA Leonhardt Ventures as well as Leonhardt's Launchpads Utah, Inc. and Leonhardt's Launchpads Australia PTY.
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