Sunday, November 19, 2017

New non-drug fix for HIV?

June 30, 2009 by  
Filed under Cyclodextrin News, HIV-Aids

The Scientist Magazine
By Alison McCook
June 2009


logoResearchers are slowly establishing a connection between an extremely rare genetic disease and HIV — and homing in on a safe, non-prescription compound that could treat both. Recently, James Hildreth at the Meharry Medical College School of Medicine in Nashville, Tenn., and his colleagues found that cells affected by Niemann-Pick Type C (NPC), which disrupts cholesterol trafficking, were unable to release HIV, suggesting these cells would not spread the virus.

These findings, published May 27 in the Journal of Virology, are rooted in a hypothesis Hildreth has explored for a long time: that "cholesterol is somehow essential" to HIV, he said. For instance, HIV-1 relies on specialized structures known as lipid rafts, which are rich in cholesterol, to infect new cells. That line of thinking has led him to investigate whether a compound widely employed by the food and chemical industries (and used as a drug solubilizer) which depletes cells of cholesterol could serve as a preventative agent — or even a treatment — for HIV. And his growing body of evidence is suggesting the compound, known as cyclodextrin, might do just that. "There are very few [compounds] that rival the safety profile" of cyclodextrin, said Hildreth. If further research confirms it has an effect on a disease that affects millions of people worldwide, that would be a major advance, he noted. "It’s been exciting for me from the beginning."

Cyclodextrin appears to also show some benefit in NPC, pointing further to a connection between HIV and the rare genetic disease. Indeed, a family with identical 5-year-old twins with NPC recently received permission from the US Food and Drug Administration to give the girls regular infusions of cyclodextrin. NPC leads to marked abnormalities in the liver and brain and is invariably fatal. "You have no idea what a relief it is to have something to try," said Chris Hempel, mother to Addi and Cassi.

The girls have so far received several infusions, starting with one continuous 4-day infusion, and are now getting a series of 8-hour weekly infusions of increasing doses. Hempel said the girls improved remarkably after the first 4-day infusion, showing better control of their head and neck and better balance, and were more affectionate and responsive to people. These improvements waned a bit once the girls switched to weekly doses, but seem to be returning as the doses increase.

In a previous experiment, Hildreth and his colleagues found that adding cyclodextrin to uninfected cells to deplete cellular cholesterol warded off HIV infection. Restoring normal cholesterol levels removed that protection. In a mouse model of HIV, cyclodextrin prevented vaginal transmission of the virus by infected cells. In a primate model, the data were somewhat less promising. When macaques received topical cyclodextrin before being exposed to the virus, the treatment appeared to prevent infection initially, but offered little protection upon re-exposure to SIV, again following cyclodextrin prophylaxis.

Hildreth said that may be because the animals received a massive dose of the virus — "way more than you’d ever see in seminal fluid in a natural setting" — and the batches of cyclodextrin used for the repeated doses were not of the same quality. He said he is now repeating the study using a "physiologically relevant" amount of the virus. "We’re pretty confident." Hildreth explained that NPC is likely disrupting HIV transmission by affecting the trafficking of the viral protein Gag. "The very dramatic thing in NPC cells is the Gag protein seems to never make it to the plasma membrane."

Currently, Hildreth is developing cyclodextrin as a microbicide against HIV. He has filed an investigational new drug application with the FDA, and is investigating whether the compound could serve as a therapeutic. Steven Walkley, who studies lysosomal storage disorders such as NPC at Albert Einstein College of Medicine in New York, said his own data show cyclodextrin has a "remarkable" effect on mice with NPC. "They’re living literally twice as long as they would otherwise, " he said. "We were very surprised, to say the least." (He and his colleagues have submitted their findings for publication.)

Walkley noted that his mice receive 4000 milligrams per kilogram of cyclodextrin — 10 times a recent dose the Hempel girls received — and he hasn’t noticed any side effects. However, it’s still unclear how exactly cyclodextrin is warding off NPC, which means there could be some side effects scientists have not yet discovered, he added. "Maybe there’s something going on and we just haven’t found it yet."

Peter Pentchev, a retired scientist who worked with NPC for decades at the National Institutes of Health, echoed Walkley’s opinion about the promise of cyclodextrin in NPC, dubbing it the "perfect drug" for the disease. He cautioned, though, that "we know what [cyclodextrin] does, but we don’t know why or how." But scientists are working on those questions, he added. "In the next year, I’d be really surprised if we don’t get some answers."

Hempel, too, has failed to notice a single side effect since her girls began cyclodextrin infusions. "We’re proving the safety of this compound," she said. "I definitely feel like Addi and Cassi are leading the way here, not only for NPC kids, but potentially for AIDS patients."

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Wacker Chemie Expands US Based Cyclodextrin Facility – Sugar Compound Poses No Known Health Risks

June 12, 2009 by  
Filed under Cyclodextrin News

Wacker Chemie, the Munich-based chemical company, announced that is has expanded its US based cyclodextrin facility in Eddyville, Iowa.  According the the press release issued by Wacker, the new cyclodextrin facility increases the company’s capacity for alpha (α) and beta (β) cyclodextrins by 50 percent and doubles its capacity for gamma (γ) cyclodextrins. Investment in the entire facility totaled over $21 million and will enable Wacker to produce up to 7,500 metric tons of cyclodextrins a year.  The extra capacity is needed to meet the worldwide rise in cyclodextrin demand.

According to the press release, “the ability to reversibly enclose other substances makes cyclodextrins invaluable in many products such as pharmaceuticals, cosmetics, textiles and food, not to mention in the household-care, personal-care and construction sectors.” What about entrapping cholesterol in the human body and helping get rid of it?

Interestingly, Wacker’s press release does not mention hydroxy propel beta cyclodextrin (HPBCD) and its potential health benefits. This is the type of cyclodextrin we are giving via intravenous infusions to Addi and Cassi for their fatal cholesterol metabolism disease, Niemann Pick Type C (otherwise known as the “Childhood Alzhiemer’s.”)   Hydroxy propel beta cyclodextrin is somehow grabbing the stuck cholesterol and taking it out of the twins’ bodies through urine/stool. I wonder if Wacker even knows of this cyclodextrin project or the fact that HPBCD also kills the HIV AIDS virus.

Here are some great facts on cyclodextrins from Wacker:

  • Cyclodextrins are cyclic sugar molecules. The number of glucose units defines the size of the sugar ring – alpha-cyclodextrin has six, beta-cyclodextrin seven, and gamma-cyclodextrin eight glucose units
  • Cyclodextrins have the ability to reversibly enclose other substances making cyclodextrins invaluable in many products such as pharmaceuticals, cosmetics, textiles and food, household and personal-care
  • Cyclodextrins are able to enclose other substances in their interiors, much like a cone encloses a scoop of ice-cream. This enables cyclodextrins to bind ingredients, release active agents and stabilize sensitive substances such as vitamins and coenzyme

The best part of the whole announcement was this statement — cyclodextrins of all types are non-toxic, non-allergenic and pose no known health risks based on today’s scientific findings!

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Extra TV Renegade Doctors Show Covers FDA Approval of Addi and Cassi’s Cyclodextrin Infusions

June 12, 2009 by  
Filed under Videos

Renegade Doctors (Extra) Story about Addi & Cassi Hempel’s Infusions of Cyclodextrin from Addi & Cassi Hempel on Vimeo.

Twins Addison and Cassidy Hempel are fighting a disease that steals their memory, but they’re only five years old. Now their mother Chris is on a crusade to stop Niemann-Pick Disease Type C, a disease similar to Alzheimer’s.

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Ten Tips To Start Your Own Virtual BioTech To Find Treatments For Your Rare Disease

June 9, 2009 by  
Filed under Virtual BioTechs

Bingo-10-580

Ever since we went public with Addi and Cassi’s cyclodextrin treatments, I have received countless emails asking me a number of questions.  How did I find the sugar compound "cyclodextrin?"  How did I manage to get the Food and Drug Administration to approve infusions of this new compound into Addi and Cassi?  As a parent advocate, would I share any knowledge I might have with others facing Rare Diseases?

Before I answer specific questions about the twins’ cyclodextrin treatments, I think it’s important to share 10 Important Lessons I have learned about the drug development process and why I have helped start a Virtual BioTech after Addi and Cassi were diagnosed with Niemann Pick Type C a year and a half ago.

Lesson 1:  Understand the drug development landscape: Most pharmaceutical companies will not be of help to you if you are facing a Rare Disease.  Here are the stats.  Approximately 7000 different Rare Diseases exist.  According to the National Institutes of Health, pharmaceutical companies have only developed treatments for 200 of the 7000 Rare Diseases!  Thousands of Rare Diseases are not being invested in by pharmaceutical companies because of small patient populations and lack of financial incentives to Pharmaceutical and Biotech companies.  This is why the NIH and NCGC have started the Therapeutics for Rare and Neglected Diseases program (TRND).  The government has to step in where Pharma and Biotech companies will not.

Lesson 2: What is in the pipeline?:  It takes 10+ years to bring a new drug to market and costs 800+ million – if a drug is not already in Phase 2 or 3 for your specific Rare Disease, it’s unlikely that there will be options for you other that what already exists.  In most cases, there will be nothing for you or your child since no drug company is going to spend $800+ million dollars on your Rare Disease.  How do you find treatments and therapies?

Lesson 3:  Create a Virtual BioTech.:  Anyone can do this.  In the case of Niemann Pick Type C disease, our family has teamed up with three other families (still looking for more to join us!) and we have pooled our resources together to find near term therapies for our children.  We named our Virtual BioTech "SOAR-NPC" or Support Of Accelerated Research for Niemann Pick Type C.  Last year, the four families raised over $1Million dollars collectively and we are pouring our money into specific NPC research projects.

Lesson 4:  Fund collaborative research teams: Currently our Virtual Biotech has 4 key NPC researchers with different skill sets working together and sharing their data.  These researchers have agreements with their respective institutions so that they can work together.   They work in different parts of the world but talk bi-monthly (before they would meet once a year at a conference) about project plans, deliverables and dividing up the research work.  This type of cooperation also reduces duplication of research efforts in laboratories.

Lesson 5:  It’s a Business. Hold Weekly Meetings: The SOAR NPC Parents group meets weekly by conference call and at least quarterly in person.   We have an agenda that we review that covers topics ranging from fundraising  to research.   Notes are taken.  We divide up tasks that need to be accomplished based on the skill sets of the team.

Lesson 6:  Project Managers: We have hired a doctor with a neuroscience background to help us understand the medical literature and he interfaces with our core set of researchers to stay abreast of all current research.   This doctor also helped us design and write the FDA protocol on cyclodextrin and is a shared resource for the families.  Parents also need to act as Project Managers depending on how much time they can devote to their cause.

Lesson 7:   A Focus on Therapies: Off Label Drugs and Supplements: Our researchers are tasked with finding near term treatments for Niemann Pick Type C affected children.  We are not focused on finding new drugs to be taken through the  pharmaceutical or biotech development process because drugs will not reach our children in time (remember it costs $800+ million to bring a new drug to market).   Rather our focus is on the library of already approved 3,000+ FDA drugs that could be used “off label” and re-purposed for our needs.  In addition, we are testing over the counter supplements that could be used to help our children today.  We have created a master drug and supplement intervention list (“our pipeline”) and have prioritized targets for testing.  Next, we test these targets in the Niemann Pick Type C mouse model or in cell based assays.

Lesson 8:  Get Involved: It’s not always possible to rely on existing non-profit Foundations to meet your personal objectives.  Understand what your Foundations are doing and where they are spending their research dollars.  For example, look at the Cystic Fibrosis Foundation which has a terrific model — they publish their drug and supplement pipeline list.  Does the Foundation supporting your Rare Disease have a drug development pipeline?  If so, ask to see it.  Some Foundations may spend their dollars on patient support while others have a focus on basic research that will not produce near term therapies for your Rare Disease.

Lesson 9:  Consider treatment options from other diseases that have more research funding: In the case of NPC, there are lots of common symptoms and pathways shared with Alzheimer’s as well as Ataxias.   A lot of research has been done in other fields that could be translated to your specific rare disease.  For example, Curcumin, a spice from Turmeric, is a good example of a non toxic supplement therapy that has shown to be beneficial in many neurological diseases.   But always do your research as there are differences between over the counter supplements. In the case of Curcumin, there is a therapeutic version developed by UCLA Curcumin experts and made by Verdure Sciences and plain over the counter that is not highly bioavaiable in your body.

Lesson 10:  Don’t take “No” for an answer: Work with people who believe in the power of “Yes.”

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Anthrax Bacteria Killed By Simple Sugar Compound Called Cyclodextrin. Is CDC Looking Into This?

June 9, 2009 by  
Filed under Cyclodextrin

We all remember the Anthrax-laced letters that killed five people and severely rattled the country post-9/11. Just when you thought there might not be a way to stop this lethal infectious disease along comes beta cyclodextrin, a non toxic sugar compound.

A researcher by the name of Vladimir Karginov at a company called Innovative Biologics is working with beta cyclodextrin and Anthrax.  Karginov has designed and synthesized a number of beta-cyclodextrin derivatives and evaluated their ability to inhibit the lethal toxin action of Anthrax.  Several compounds displayed anti-toxin activity at low micromolar concentrations in cell-based assays and preliminary toxicity and efficacy studies in rodents produced very promising results.  You can read about the research project here.

Anthrax is a highly lethal and infectious disease caused by the bacterium Bacillus anthracis, a bacteria that forms spores, or dormant cells, which can come to life under the right temperature, nutrients and other conditions to allow growth. Anthrax occurs in humans after exposure to an infected animal or infected animal tissue or when anthrax spores are used as a bioterrorist weapon.  

There are some effective vaccines against anthrax, and some forms of the disease respond well to antibiotic treatment shortly after exposure. But there is need for new, safe and effective treatments approved by the FDA to supplement traditional intravenous and oral antibiotic therapy such ciprofloxacin (cipro), doxycycline or vancomycin. I have now reported on beta cyclodextrins ability to kill the HIV AIDS virus and now the deadly Anthrax bacterium.  This same non toxic sugar compound is also being used to treat my 5 year old identical twins who have a fatal cholesterol metabolism disorder called Niemann Pick Type C, or the "childhood Alzheimer’s."

What other lethal bacterias and viruses does this non toxic cyclodextrin compound kill?   What does the Centers of Disease Control and Prevention and the United States Department of Health and Human Services know about cyclodextrin and are they studying it?

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