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Post by itellthefuture777 on Apr 1, 2020 15:38:56 GMT -5
medium.com/@stkirsch/getting-large-rcts-done-asap-on-all-our-most-promising-options-is-the-best-way-to-end-the-covid-19-53bc842f4eff
Anyone know who this is working with Mannkind??
Micronized niclosamide
"A recent study highlighted niclosamide as one of just two “best drugs” to pursue from an in vitro screen over 50 FDA approved drugs. It has a super high selectivity index (SI): 176! It was shown 16 years ago to inhibit SARS-CoV replication. The problem though is bioavailability: taken as a pill, it just sits in the stomach. However, by micronizing the drug, it can be put in an inhaler and thus be delivered directly to the affected tissue. We already have the GMP micronized drug available; it just needs to be delivered using an inhaler vehicle. This can be used as a prophylaxis to avoid the risk of pulmonary fibrosis.
Niclosamide s hows several mechanisms of activity against flaviviruses — including endosome neutralization. It is likely that endosomes are main route of SARS and SARS-CoV2 entry — that’s how hydroxychloroquine and chloroquine are thought to act — good evidence for that in vitro in non-lung cell lines (not yet in lung cells). Another mechanism is intracellular acidification and inflammasome activation — along with mitochondrial uncoupling. Since mitochondrial uncoupling is how it kills parasites — this is likely mechanism of toxicity to human cells as well.
What’s really cool is we can eliminate most of the guesswork out of dose and frequency because we can now see exactly what is going on in real-time using CT. Watch this video: (video is in link)
So we just need a company with the technology to mix with excipients and deliver this in an inhaled form and a PI willing to trial it. Thanks to assistance from Laurie Glimcher, Greg Petsko, Nitin Joshi, Yohannes Tesfaigzi, Frances Laur, and Robert Rubin, we are currently working with Phil Kuehl at Lovelace Biomedical (and LRRI). We are also being helped by Michael Castagna, CEO of MannKind who makes the Afrezza insulin inhaler that I’ve personally used in the past with excellent results.
Even though the drug is FDA approved, because this drug is being delivered in a novel way, we have to start with a Phase 1b safety study in 20 patients, but we’ll likely be able to get a good feeling of effectiveness from that.
This treatment is a great match for the disease because it is targeted and lethal (SI=176).
The receptors for the virus are in the upper GI tract, which is where it begins life. It later migrates down your GI into both the stomach and the lungs. This is why people report stomach issues. Only late stage does it migrate to the bloodstream.
Niclosamide could also be tested in patients right now by prescribing niclosamide, though I’m not sure how you’d be able to assess the viral load in your stomach.
The nice benefit of this treatment is that it is targeted delivery and reduces viral shedding. This is important in both directions: up and down. It is the viral shedding that enables the virus to drop down into your lungs and stomach. So if we can kill it off early in the GI tract, we win. No lung infection! And in the reverse direction, it keeps you from spreading it. So you get a three-fer effect: it cures you, it prevents your lungs being impacted, and it prevents you from spreading the disease to others.
We need to test this for use in 3 different scenarios: pre-infection, post-infection, and onset of symptoms. It could be the perfect prophylactic.
All the credit for this idea goes to Lynda Chin and Gary Glick, CEO of First Wave Bio. They were working on a treatment for colitis and Lynda realized they could repurpose their niclosamide micronization efforts for SAR-CoV-2.
As for how I found out about this, it was just dumb luck. I’ve known Lynda and her husband, Ron DePinho, for 20 years and we accidentally got reconnected after all this time by Shyamali Singhal, Director of the Cancer Center at El Camino Hospital who I reached out to see how things were going at my local hospital. Shyamali said she was working with Lynda Chin on a joint project. I never thought it was the same Lynda Chin I met 20 years earlier! Oddly, I was simultaneously reaching out directly to Ron DePinho to get his thoughts (I thought Ron would not be overwhelmed but I was wrong). So it was just a really remarkable coincidence to re-make this double connection two separate ways after a 20 year hiatus! Not only a random reconnect after a 20 year hiatus, but the fact that Lynda happened to be involved in the same drug I had identified as promising earlier was simply a remarkable coincidence. When she mentioned niclosamide when we talked, my jaw dropped.
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Post by goyocafe on Apr 1, 2020 15:47:12 GMT -5
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Post by itellthefuture777 on Apr 1, 2020 16:41:45 GMT -5
Thanks! My research of this item so far is noted as the safest by WHO..so..also very anti cancer..anti a lot of things more than just Covid..
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Post by goyocafe on Apr 1, 2020 17:36:55 GMT -5
Thanks! My research of this item so far is noted as the safest by WHO..so..also very anti cancer..anti a lot of things more than just Covid.. I think your post deserves its own thread. And I would really like to understand what Mannkind's involvement is in all of this. It's a glimmer of hope to say the least.
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Post by centralcoastinvestor on Apr 1, 2020 18:32:22 GMT -5
Thanks! My research of this item so far is noted as the safest by WHO..so..also very anti cancer..anti a lot of things more than just Covid.. I think your post deserves its own thread. And I would really like to understand what Mannkind's involvement is in all of this. It's a glimmer of hope to say the least. I agree. If MannKind is involved with direct treatment of Covid_19. That deserves its own thread posted in the All About MannKind folder. Title the Thread: Is MannKind involved with a direct solution to Covid_19?
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Post by boytroy88 on Apr 1, 2020 18:54:39 GMT -5
Let's hope this gets out to the newswire and maybe move our SP some...
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Post by peppy on Apr 1, 2020 19:14:44 GMT -5
medium.com/@stkirsch/getting-large-rcts-done-asap-on-all-our-most-promising-options-is-the-best-way-to-end-the-covid-19-53bc842f4eff
Anyone know who this is working with Mannkind??
Micronized niclosamide
"A recent study highlighted niclosamide as one of just two “best drugs” to pursue from an in vitro screen over 50 FDA approved drugs. It has a super high selectivity index (SI): 176! It was shown 16 years ago to inhibit SARS-CoV replication. The problem though is bioavailability: taken as a pill, it just sits in the stomach. However, by micronizing the drug, it can be put in an inhaler and thus be delivered directly to the affected tissue. We already have the GMP micronized drug available; it just needs to be delivered using an inhaler vehicle. This can be used as a prophylaxis to avoid the risk of pulmonary fibrosis.
Niclosamide s hows several mechanisms of activity against flaviviruses — including endosome neutralization. It is likely that endosomes are main route of SARS and SARS-CoV2 entry — that’s how hydroxychloroquine and chloroquine are thought to act — good evidence for that in vitro in non-lung cell lines (not yet in lung cells). Another mechanism is intracellular acidification and inflammasome activation — along with mitochondrial uncoupling. Since mitochondrial uncoupling is how it kills parasites — this is likely mechanism of toxicity to human cells as well.
What’s really cool is we can eliminate most of the guesswork out of dose and frequency because we can now see exactly what is going on in real-time using CT. Watch this video: (video is in link)
So we just need a company with the technology to mix with excipients and deliver this in an inhaled form and a PI willing to trial it. Thanks to assistance from Laurie Glimcher, Greg Petsko, Nitin Joshi, Yohannes Tesfaigzi, Frances Laur, and Robert Rubin, we are currently working with Phil Kuehl at Lovelace Biomedical (and LRRI). We are also being helped by Michael Castagna, CEO of MannKind who makes the Afrezza insulin inhaler that I’ve personally used in the past with excellent results.
Even though the drug is FDA approved, because this drug is being delivered in a novel way, we have to start with a Phase 1b safety study in 20 patients, but we’ll likely be able to get a good feeling of effectiveness from that.
This treatment is a great match for the disease because it is targeted and lethal (SI=176).
The receptors for the virus are in the upper GI tract, which is where it begins life. It later migrates down your GI into both the stomach and the lungs. This is why people report stomach issues. Only late stage does it migrate to the bloodstream.
Niclosamide could also be tested in patients right now by prescribing niclosamide, though I’m not sure how you’d be able to assess the viral load in your stomach.
The nice benefit of this treatment is that it is targeted delivery and reduces viral shedding. This is important in both directions: up and down. It is the viral shedding that enables the virus to drop down into your lungs and stomach. So if we can kill it off early in the GI tract, we win. No lung infection! And in the reverse direction, it keeps you from spreading it. So you get a three-fer effect: it cures you, it prevents your lungs being impacted, and it prevents you from spreading the disease to others.
We need to test this for use in 3 different scenarios: pre-infection, post-infection, and onset of symptoms. It could be the perfect prophylactic.
All the credit for this idea goes to Lynda Chin and Gary Glick, CEO of First Wave Bio. They were working on a treatment for colitis and Lynda realized they could repurpose their niclosamide micronization efforts for SAR-CoV-2.
As for how I found out about this, it was just dumb luck. I’ve known Lynda and her husband, Ron DePinho, for 20 years and we accidentally got reconnected after all this time by Shyamali Singhal, Director of the Cancer Center at El Camino Hospital who I reached out to see how things were going at my local hospital. Shyamali said she was working with Lynda Chin on a joint project. I never thought it was the same Lynda Chin I met 20 years earlier! Oddly, I was simultaneously reaching out directly to Ron DePinho to get his thoughts (I thought Ron would not be overwhelmed but I was wrong). So it was just a really remarkable coincidence to re-make this double connection two separate ways after a 20 year hiatus! Not only a random reconnect after a 20 year hiatus, but the fact that Lynda happened to be involved in the same drug I had identified as promising earlier was simply a remarkable coincidence. When she mentioned niclosamide when we talked, my jaw dropped.
Niclosamide (Oral) ni-KLOE-sa-mide Medically reviewed by Drugs.com. Last updated on Oct 19, 2019. www.drugs.com/cons/niclosamide.htmlUses for niclosamide Niclosamide belongs to the family of medicines called anthelmintics. Anthelmintics are medicines used in the treatment of worm infections. Niclosamide is used to treat broad or fish tapeworm, dwarf tapeworm, and beef tapeworm infections. Niclosamide may also be used for other tapeworm infections as determined by your doctor. It will not work for other types of worm infections (for example, pinworms or roundworms). Niclosamide works by killing tapeworms on contact. The killed worms are then passed in the stool. However, you may not notice them since they are sometimes destroyed in the intestine. Niclosamide is available only with your doctor's prescription.
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Post by cjm18 on Apr 1, 2020 19:27:59 GMT -5
Mc is one of the names at the bottom. He helped the author write the article.
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Post by nylefty on Apr 1, 2020 19:31:18 GMT -5
The article was written by Steve Kirsch, an Afrezza user and good guy for Mike to know.
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Post by brotherm1 on Apr 1, 2020 20:50:47 GMT -5
So are they in touch with the D.O.D., DARPA, BARDA, The WHO, the Gates Foundation, CEPI , CDC...?
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Post by nylefty on Apr 1, 2020 21:31:04 GMT -5
More on Steve Kirsch, from his LinkedIn profile: About
Serial high tech entrepreneur and philanthropist. I've founded 7 companies, 2 with billion dollar valuations.
My current venture, M10, is developing a very unique approach to digital money. It has the benefits of CBDC without the downsides. It enables users to directly send cross border payments instantly and securely with instant settlement. We eliminate the need for traditional nostro accounts and correspondent banking, making this also an ideal solution for banks who have difficulty getting a nostro account. Our approach digitizes both M0 and M1 money (hence the name of the company). It increases efficiency (automating liquidity management) and reduces risk (giving an independent set of eyes on sanctions and AML). We think our unique approach to digital money is the future of money due to the significant benefits for all players: central banks, banks, corporations, software developers, consumers. It was designed as a payment modernization tool for Central Banks to encourage their member banks deploy in their country so that the banks remain competitive and healthy. You can think of it as version 2 of UPI which has, in just a few short years, eclipsed all other forms of payment in India.
I love tackling really hard problems. My innovations have spanned a broad range: optical mouse, Internet search, desktop publishing, spam filtering, Internet acceleration, secure federated identity, and open banking. I'm on the Technology Advisory Board at HSBC.
I'm a proponent of nuclear power to help solve the global warming problem. I was an Executive Producer of "Pandora's Promise."
I helped rid the US of junk faxes (junkfax.org).
Married >25 years; 3 daughters.
I've been involved with computers for 50 years (since I was 10 years old). I've programmed in almost two dozen languages, and was lucky enough to work with the pioneers of the Internet while I was in junior high school. I shared an office with Jon Postel at UCLA (he wrote the email protocol we use today). I wrote the email program used by the Internet inventors at UCLA.
Charitable foundation: www.kirschfoundation.org
The Computer Science Auditorium at MIT (Kirsch Auditorium) is named after me (but to be honest, a multi-million dollar gift influenced that decision).
Interests: Making a the world a better place, improving the user experience in banking/payments, identity, cybersecurity, entrepreneurship, philanthropy, waldenstrom's macroglobulinemia, glaucoma, type 2 diabetes.
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Post by itellthefuture777 on Apr 1, 2020 22:11:12 GMT -5
www.ncbi.nlm.nih.gov/pmc/articles/PMC4166407/Interesting read Also the absorption is very low in pill form...so inhaled is the way to go..as we know pills lose 95% of active drug in stomach acid and only 5% get to target..better to bypass the stomach and treat to target (lung)..imo...also for Covid there was a blur about Bayer investigating this same drug..and they already know..pills are not the way to go...wonder what might happen..hmm
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Post by itellthefuture777 on Apr 2, 2020 3:32:39 GMT -5
www.ncbi.nlm.nih.gov/pubmed/25974285 Toward Repositioning Niclosamide for Antivirulence Therapy of Pseudomonas aeruginosa Lung Infections: Development of Inhalable Formulations through Nanosuspension Technology. Costabile G1, d'Angelo I2, Rampioni G3, Bondì R3, Pompili B4, Ascenzioni F4, Mitidieri E1, d'Emmanuele di Villa Bianca R1, Sorrentino R1, Miro A1, Quaglia F1, Imperi F4, Leoni L3, Ungaro F1. Author information Abstract Inhaled antivirulence drugs are currently considered a promising therapeutic option to treat Pseudomonas aeruginosa lung infections in cystic fibrosis (CF). We have recently shown that the anthelmintic drug niclosamide (NCL) has strong quorum sensing (QS) inhibiting activity against P. aeruginosa and could be repurposed as an antivirulence drug. In this work, we developed dry powders containing NCL nanoparticles that can be reconstituted in saline solution to produce inhalable nanosuspensions. NCL nanoparticles were produced by high-pressure homogenization (HPH) using polysorbate 20 or polysorbate 80 as stabilizers. After 20 cycles of HPH, all formulations showed similar properties in the form of needle-shape nanocrystals with a hydrodynamic diameter of approximately 450 nm and a zeta potential of -20 mV. Nanosuspensions stabilized with polysorbate 80 at 10% w/w to NCL (T80_10) showed an optimal solubility profile in simulated interstitial lung fluid. T80_10 was successfully dried into mannitol-based dry powder by spray drying. Dry powder (T80_10 DP) was reconstituted in saline solution and showed optimal in vitro aerosol performance. Both T80_10 and T80_10 DP were able to inhibit P. aeruginosa QS at NCL concentrations of 2.5-10 μM. NCL, and these formulations did not significantly affect the viability of CF bronchial epithelial cells in vitro at microbiologically active concentrations (i.e., ≤10 μM). In vivo acute toxicity studies in rats confirmed no observable toxicity of the NCL T80_10 DP formulation upon intratracheal administration at a concentration 100-fold higher than the anti-QS activity concentration. These preliminary results suggest that NCL repurposed in the form of inhalable nanosuspensions has great potential for the local treatment of P. aeruginosa lung infections as in the case of CF patients. KEYWORDS: Pseudomonas aeruginosa; antivirulence drugs; cystic fibrosis; nanosuspensions; niclosamide; pulmonary delivery; quorum sensing; rat
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Post by itellthefuture777 on Apr 2, 2020 3:34:38 GMT -5
www.ncbi.nlm.nih.gov/pubmed/32125140ACS Infect Dis. 2020 Mar 10. doi: 10.1021/acsinfecdis.0c00052. [Epub ahead of print] Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential. Xu J, Shi PY, Li H1, Zhou J. Author information Abstract The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV, and human adenovirus, indicating its potential as an antiviral agent. In this brief review, we summarize the broad antiviral activity of niclosamide and highlight its potential clinical use in the treatment of COVID-19. KEYWORDS: Ebola virus; MERS-CoV; SARS-CoV; SARS-CoV-2 (COVID-19); Zika virus; broad antiviral agents; coronavirus; flavivirus; human adenovirus; niclosamide
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Post by itellthefuture777 on Apr 2, 2020 3:38:08 GMT -5
www.ncbi.nlm.nih.gov/pubmed/31969986Biomater Res. 2020 Jan 15;24:3. doi: 10.1186/s40824-020-0184-8. eCollection 2020. Emerging role of nanosuspensions in drug delivery systems. Jacob S1, Nair AB2, Shah J3. Author information Abstract Rapid advancement in drug discovery process is leading to a number of potential new drug candidates having excellent drug efficacy but limited aqueous solubility. By virtue of the submicron particle size and distinct physicochemical properties, nanosuspension has the potential ability to tackle many formulation and drug delivery issues typically associated with poorly water and lipid soluble drugs. Conventional size reduction equipment such as media mill and high-pressure homogenizers and formulation approaches such as precipitation, emulsion-solvent evaporation, solvent diffusion and microemulsion techniques can be successfully implemented to prepare and scale-up nanosuspensions. Maintaining the stability in solution as well as in solid state, resuspendability without aggregation are the key factors to be considered for the successful production and scale-up of nanosuspensions. Due to the considerable enhancement of bioavailability, adaptability for surface modification and mucoadhesion for drug targeting have significantly expanded the scope of this novel formulation strategy. The application of nanosuspensions in different drug delivery systems such as oral, ocular, brain, topical, buccal, nasal and transdermal routes are currently undergoing extensive research. Oral drug delivery of nanosuspension with receptor mediated endocytosis has the promising ability to resolve most permeability limited absorption and hepatic first-pass metabolism related issues adversely affecting bioavailability. Advancement of enabling technologies such as nanosuspension can solve many formulation challenges currently faced among protein and peptide-based pharmaceuticals. © The Author(s). 2020. KEYWORDS: Drug delivery systems; Formulation components; Manufacturing methods; Nanosuspension PMID: 31969986 PMCID: PMC6964012 DOI: 10.1186/s40824-020-0184-8 Free PMC Article
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