Tuesday, May 17, 2022

How Cyclodextrin Solution Is Made For Addi and Cassi’s Intravenous Cyclodextrin Therapy

November 25, 2009 by  
Filed under Cyclodextrin

A number of people from around the world who have children diagnosed with the fatal cholesterol disease called Niemann Pick Type C  have asked me how our we prepare our cyclodextrin solution for Addi and Cassi’s bi-weekly IV infusions of the compound.

All hydroxy propel beta cyclodextrin (HPBCD) is not the same. It’s very important that you make sure that the cyclodextrin that is purchased is endotoxin controlled and does not have propylene glycol in it or other impurities. Essentially propylene glycol is anti-freeze – not exactly what you want to put into kids!

We purchase our cyclodextrin from CTD, Inc., which is located in High Springs, Florida. The owner of CTD is extremely knowledgable when it comes to cyclodextrins and sells many different types of cyclodextrin products.  The cost for his HPBCD is about $5 USD per gram.

I am still working to try and make a solution that can be bottled and sent worldwide. As you can imagine, this takes time since we have no pharmaceutical company helping us with this effort.

When the girls receive their infusions, there is a basic filter that the cyclodextrin funnels through (this is simply as a precaution).  The filter is attached to the infusion line and as the cyclodextrin drips through the plastic line it goes through this little blue filter. I will try and find out the name of the filter we use.

We are currently looking at different ways to get cyclodextrin into the body — possibly through regular subcutaneous injections as well as intrathecal methods to get cyclodextrin directly into the brain through the spinal canal.  We are actively pursuing both ideas now on how this would be possible for Addi and Cassi.

I continue to be very happy with how the infusions are going.  The most difficult part so far has not been giving them cyclodextrin — it is being at the hospital for 2x a week all day long just sitting there watching cartoons. I am hoping the FDA will approve us to do infusions in a home setting (hopefully at night when they are sleeping) as we have not experienced any side effects.  We are at 2500 (yes, 2500) mg per Kg BW and the infusion lasts 8 hours.

Addi and Cassi seem to be a lot more alert and aware and have better balance and head control!   I pray we can speed up research on cyclodextrin and determine the mechanism for how it’s working.

For more information on Addi and Cassi’s cyclodexrin protocol, you can view our FDA compassionate use filings here.

Beware of Air Oxidized NAC Supplements – Pharmaceutical Grade N-Acetyl-Cycsteine (NAC) Boosts Glutathione Levels

November 22, 2009 by  
Filed under Featured Stories, Products We Like

Pharma-NAC-N-Acetyl-Cysteine tablets

Many papers have been published showing that people with diseases of all kinds might have problems with glutathione production in the body. In Addi and Cassi’s case, their fatal cellular cholesterol disease called Niemann Pick Type C is somehow disrupting their glutathione levels in their bodies. Over the past 9 months, we have been trying to correct this problem in the twins through administering a range of supplements.

But how do you go about picking the right supplement to increase glutathione levels in the body?  When you do Google search, hundreds of products pop up all claiming to produce instant results. Through my research, I have learned that raising glutathione levels in the body is not so easy. Simply taking Glutathione itself will not work.

Glutathione (reduced state is called GSH) is an important intracellular free radical scavenger protecting cells against oxidative stress. It is considered one of the body’s primary antioxidants and is produced naturally from three amino acids: Glycine, Glutamine, and Cysteine. Glycine, Glutamine, and Cysteine are considered precursors of glutathione.  Precursors are compounds that participate in the chemical reaction that produces another compound.

N-AcetylCysteine, otherwise know as NAC, is the leading precursor to increasing glutathione levels in the body and can help replenish intracellular GSH levels. Once NAC enters the body, it is metabolized into glutathione. Glutathione can then function as the powerful antioxidant that it is.

All NAC supplements are NOT the same. The problem I have run into with most over the counter NAC supplements is their packaging. NAC is a strong thiol-bearing compound prone to air oxidization. Once you open the bottle you bought on the Internet, the product has likely degraded since the time it was on the manufacturing line.  Bioavailabilty (the amount that actually gets into your body) is likely low.

There is a company called BioAdvantex in Canada that makes a pharmaceutical grade NAC supplement that comes in an effervescent tablet form (see photo).  Think of an Alka Seltzer with a wild berry flavor. Each PharmaNAC fizzy tablet is individually wrapped in a special paper/plastic/foil material to keep moisture and air from entering the package.  The manufacturing process is very well controlled to produce the most bioavialable form of NAC on the market today.  Each tablet comes in 900mgs which I like.

PharmaNAC is more expensive than other forms of NAC on the market.  You can purchase it online at a cost of about $1 dollar a tablet.  This is well worth the price because I don’t want to be putting supplements into my twins that have little chance of helping them.

I also found this useful list of sources that may boost glutathione levels in the body naturally.  Interestingly, one is called Curcumin, another compound I give to Addi and Cassi.  Curcumin has some of the same issues as NAC in that all supplments on the market are not the same.   I use the Curcumin developed by Dr. Greg Cole and Dr. Sally Frauchy at UCLA and made by Verdure Sciences — this is the most bioavailable form of Curcumin that I am aware of.

Does XMRV Use Cholesterol to Survive in the Body Like HIV-AIDS? What XMRV Infected Twins May Teach us about the Virus.

November 21, 2009 by  
Filed under Featured Stories

You know the old saying, “trust your instincts?”  When you get a “gut feeling” about something, pay attention to it.  Ever since Addi and Cassi first became ill with a flu like virus in 2005, my motherly instincts kicked into overdrive.

After months of being sick, I was told by Stanford doctors that Addi and Cassi were infected with a “chronic infectious mononucleosis type of syndrome.”  I never believed this to be the ultimate cause of their medical issues so I kept searching for the reason they were running into walls and falling down all the time.

In October 2007,  it was confirmed through genetic testing that Addi and Cassi have Niemann Pick Type C disease, a fatal cellular cholesterol disease that is often referred to as the “childhood Alzheimer’s.”  So why am I writing about XMRV?

Despite our NPC diagnosis, I have always believed that the virus that attacked us in 2005 was also impacting my twins’ immune system. For the past few years, I have pestered our doctors and researchers with the idea that the virus was still wrecking havoc in the girls’ systems.  No two children could possibly get all the viral infections they have contracted such as HerpesB, RotaVirus, MRSA, Coxsaxie Virus, Hand Foot and Mouth, etc.  No one seemed to believe me as there is no known immune system problem in Niemann Pick Type C disease. Or if they did believe me, they had no idea how to help.

In September 2009, I learned the truth about what else is impacting my twins’ health.  Addi and Cassi have been diagnosed with an active infection of the newly discovered retrovirus called XMRV, or Xenotropic murine leukemia virus-related virus (confirmed by two labs). XMRV has been linked to Prostate Cancer and Chronic Fatigue Syndrome and millions of people are infected with it just like Addi and Cassi and don’t even know it!  Scary!

I’m not sure whether to be sad or happy about the XMRV news. Sad because my girls are not only fighting a fatal cholesterol disease but a virus on top of it or happy because I feel vindicated and finally know the full scope of what I am dealing with.  I feel like screaming out, “I told you so!”

Here is a sampling of a few of my emails to doctors and researchers that I dug up from my Sent Mail:

“I was told their immune system is normal with response on testing but there is NO WAY it is normal.  No way.  It is not normal!”

“It’s unbelievable is all I can say.  Bizarre.  Also, they continue to not be able to get viruses under control – this is an ongoing issue.  I am wondering if their white count has dropped again?  I have cced Dr. Porter on this email – maybe he has some ideas? I also want him to know about this virus issue – they just can’t fight off the most basic of things.”

Since receiving the devastating news that our girls have Niemann Pick Type C disease, we have appeared on TV shows like The Doctor’s and DATELINE to educate people on the disease and explain what it’s like to deal with two 5 year old kids with dementia. The good news is that some people do listen.  Dr. Judy Mikovitz of the Whittemore Petersen Institute in Reno, Nevada (where I live) heard of my complaints of a “viral illness” striking our family in 2005.  She offered to do some testing.  At first nothing turned up, but I remained persistent in trying to get to the bottom of what was going on.

“Annette, I hope you are doing well.  I am so sorry I have not been in touch but I have been swamped with working with our doctors and the FDA to treat the girls with cyclodextrin. Last year, Judy ran some special testing on Addi and Cassi. I know that whatever she tested turned out negative but I am wondering what she was looking at.  Did she look at NKT cells by chance (see attached)? Something is going on with the girls’ immune systems and I am trying to get to the bottom of it. The HIV/AIDS researcher I am working with thinks that there is something going on with transcription factors and t-cells.”

“Chris, last year we looked at inflammatory cytokines and chemokines and the Rnase L activity. The cytokines and chemokines were within the normal adult ranges (though we know nothing about ranges in small children). The RNase L activity was high but that is consistent with active infection (EBV?). We only had 6 mls of blood so we could not do the panel of immune cells NK and NKT or the important T cell component. We would like to do these studies and now that we have the LSR (18 color flow cytometer up and running) we could do an in depth immune profiling. I would also like to look at the girls’ immune system in light of a recent new discovery made here at the WPI (but not yet public knowledge). If possible could we get ~15 mls from the girls this week? We have a window of opportunity before the holiday and vacations and would be delighted to do all the testing here at the WPI lab that you visited last year Applied Research facility Rm 401 on Evans. We can also pick up the blood at your convenience.”

I provided Dr. Mikovits with additional blood samples from the twins. Sure enough Addi and Cassi tested positive for an active infection of XMRV.  One twin (Cassi) tested with more severity. Cassi is the same twin that had more severe symptoms at the onset of contracting the virus. There must be something here to research further.

Interestingly, for the past year and a half I have been working with a leading HIV-AIDS researcher who discovered that the HIV-AIDS virus (also a retro virus like XMRV) uses cholesterol and the Niemann Pick Type C gene to do its dirty work in the human body. I am wondering if XMRV utilizes cholesterol and lipid rafts to do its dirty work and whether the Niemann Pick Type C gene could help the XMRV virus assemble in the body like it does with HIV-AIDS?

What most people don’t understand is that all people on the planet are born with the  Niemann Pick Type C gene.  This gene on Chromosome 18 regulates human cholesterol metabolism at the celluar level.  Addi and Cassi have two genetic defects on their NPC gene, causing their fatal cholesterol illness.  Only 500 children in the world have the double mutation on their NPC gene.

I believe the NPC gene might play a role in XMRV.  If it does, I am certain that Addi and Cassi’s active infection of XMRV will teach us something about how the virus replicates in the human body.  Addi and Cassi’s XMRV infection would not replicate and move within he cells the same way as a person who does not have genetic defects on the NPC cholesterol gene.  In fact, Addi and Cassi’s XMRV virus might be less severe than someone without the genetic defects (which makes me feel so sorry for so many people because XMRV has caused us major issues!).

The odds of identical twins having Niemann Pick Type C disease AND and active XMRV infection probably could not be calculated.  I can tell you that they are the only identical twins on the planet with NPC and XMRV.  Even though Addi and Cassi can no longer remember how to talk, I feel like they are screaming out to everyone too!

Nobel Prize Winning Cholesterol Researchers Brown and Goldstein Enter Cyclodextrin Field Of Study

November 10, 2009 by  
Filed under Featured Stories

I wonder how many smart cholesterol researchers have Google Alerts set up on Brown and Goldstein Labs?  If they do they might want to read this post about the Nobel Prize winning labs release of a very important cholesterol paper involving cyclodextrin and its modulation of cellular cholesterol metabolism.

With their amazing new research work, Brown and Goldstein have shown that cyclodextrin (hydroxy propel beta cyclodextrin or HPBCD) reverses the block in cholesterol movement out of the lysosome in cultured cells of both the mouse and human Niemann Pick Type C fibroblasts.  The papers are here:

Brown and Goldstein Paper – Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport in Niemann-Pick type C cells

Brown and Goldstein Supplemental Information on Niemann Pick Type C, Cholesterol and Cyclodextrin

For those of you who have no idea what I am talking about, this is very big news in the world of cholesterol research. It’s not every day that Nobel Prize winning cholesterol scientists publish papers on a non toxic sugar compound that is the main ingredient in Febreze air freshener and  fat free food products like butter.

How on earth can cyclodextrin be entering the cell and the lysosome and reversing the Niemann Pick Type C cholesterol genetic defect that is trying to kill our twin daughters?

In this paper, Brown and Goldstein say that the mode of action of cyclodextrin is still unknown. This is remarkable to me because the most famous cholesterol researchers on the planet have been unable to figure out this scientific puzzle. When this is all sorted out, I think a whole new wave of drugs will be developed with this compound that everyone has thought is benign!  I hope it happens fast because this compound could save my girls’ lives.

In conjunction with this news from Brown and Goldstein, Addi and Cassi’s lysosomes are shrinking in size since receiving their cyclodextrin IV infusions.  Measurements of Addi and Cassi’s lysosomes were done with a special assay developed at Oxford University. But is cyclodextrin really crossing the cell membrane and going into the cells in living people?   The previous research on cyclodextrin would say it acts outside the cell membrane.

Addi and Cassi are now six months into their cyclodextrin infusions which were approved by the FDA under “compassionate use” IND applications.  Addi and Cassi are doing quite well with no apparent side effects (except positive effects like better balance and coordination and increased concentration and awareness). But how can this be happening if cyclodextrin does not get through the blood brain barrier?

The data in the twins’ lysosomes  indicates what Brown and Goldstein has found in mice and in cell culture/ fibroblasts could be happening inside Addi and Cassi’s systems as well.  Our next step will be to apply for Orphan Drug Status with the FDA for Cyclodextrin after Thanksgiving.  I am also working with doctors on ways to get cyclodextrin across the blood brain barrier.  I am currently pursing a path to get Cyclodextrin into the CSF of Addi and Cassi.  I think if we can do this we have a better chance to save them from this horrible cholesterol disease that is destroying their brains and causing dementia.

We are going to apply for a FDA grant in February 2010. Cyclodextrin kills the HIV-AIDS virus too.  If we can get the goverment to keep and open mind and get more researchers studying this compound, the possibilities are endless.

ResearchMatch.org Is Cool -The Idea, the Website and even the Logo! Is This Really From The NIH?

November 10, 2009 by  
Filed under Featured Stories

Great news from the NIH today — a new service called ResearchMatch.org was announced.  ResearchMatch.org is a national research study recruitment registry announced to help match volunteers with researchers who want them to participate in research studies.

The registries matching model compliments Clinicaltrials.gov (a website that needs a serious facelift!) but  has one fundamental difference. ResearchMatch.org places the burden of connecting the right volunteers with the right study on the researchers, whereas Clinicaltrials.gov asks volunteers to identify the trials that could work for them.

I am going to have my entire family sign up to be part of ResearchMatch.  Imagine if everyone did the same. Researchers could easily find people to participate in studies which in turn would speed up finding treatments and cures for diseases.  One of the biggest problems in research studies today is that a certain number of people are needed to participate in order to find answers but often times there are too few volunteers.  This is a problem we face in Niemann Pick Type C disease — with only 500 children in the world with the disease we have limited volunteers and a small cohort for clinical studies.

Many things created by our government tend to be overly complicated or fall short of their promise. However, ResearchMatch is a smart idea and the website is user friendly and easy to navigate.  In fact, the website is so nice compared to other government websites I have visited that it actually looks like someone in the private sector created it!  Even the logo is cool!

The process to sign up to participate in ResearchMatch was simple and took me about 5 minutes to complete. Anyone can join too — many research studies are looking for healthy volunteers or “controls.”

Join today and spread the word and contribute to the greater good — https://www.researchmatch.org/