Chronic Fatigue Virus Saga Continues – Murine Leukemia Virus or MLV Found by FDA and NIH

The chronic fatigue virus saga continues. Today, the NIH, FDA and CDC held a teleconference and provided additional evidence of an association between a virus and Chronic Fatigue Syndrome. But instead of focusing directly on XMRV like I thought they would, most of the call was centered on a family of viruses called murine leukemia virus-related virus or MLV.  Apparently, XMRV is one of several viruses of the MLV virus family.

Blood samples from more than 80% of patients with chronic fatigue syndrome were tested and found to have viral gene sequences and genetic code similar to those of murine leukemia virus (or MLV) which causes leukemia in mice.

The government researchers noted considerable genetic diversity among the MLV-like viruses they found in their CFS patients rather than the homogeneity of xenotropic murine leukemia virus-related virus (XMRV) linked in other studies to chronic fatigue syndrome. The researchers reported finding three distinct types of MLV-related virus gag sequences which apparently are more closely related to sequences of polytropic mouse endogenous retroviruses than to XMRV. XMRV is among several different members of the MLV family, researchers said.

The researchers, including Dr. Shyh Ching Lo of the FDA and Dr. Harvey Alter of NIH, we careful to not confirm that an infectious agent like MLV or XMRV causes Chronic Fatigue Syndrome. The good news is they were on the record to say they believe the central argument by the Whittemore Peterson Institute.  They also said that WPI is now finding more genetic diversity in their CFS patients after doing further studies.

The researchers also discussed the need to continue the investigation of XMRV, MLV, and chronic fatigue syndrome. I hope they will take it further. My six year old identical twins are infected with XMRV and we need studies on children that that have genetic conditions like Niemann Pick Type C combined with XMRV infection — do they influence each other?  I believe they do. Many kids like Addi and Cassi are dealing with two severe conditions at the same time — genetic conditions combined with viruses.  Also, I am going to talk to Dr. Caroline Hastings, who not only treats Addi and Cassi, but also kids with leukemia. I am wondering if her patients would test positive for either of these viruses?

NIH press release is here: http://www.prnewswire.com/news-releases/study-presence-of-murine-leukemia-virus-related-gene-sequences-found-in-cfs-patients-101316939.html

Scientists at NIH, FDA & CDC To Hold Briefing On XMRV Retrovirus

Note: I plan to begin posting blogs about the XMRV retrovirus on Addi and Cassi’s website. Why would I start posting about XMRV when Addi and Cassi have Niemann Pick Type C disease, a fatal “childhood Alzheimer’s” like condition? People who are reading my blog for the first time need to know that all people are born with the Niemann Pick Type C gene. This critical gene on Chromosome 18 regulates cholesterol metabolism at the cellular level, and unlike Addi and Cassi who were born with a double genetic mutation on their Niemann Pick cholesterol gene, most people are born with healthy non-mutated NPC genes.

Addi and Cassi have been confirmed to be positive for XMRV, a human gamma retrovirus that finally may be confirmed by the NIH and FDA today. Retroviruses like XMRV and HIV-AIDS insert into your genetic material and stay for life and millions of people worldwide are suspected to be infected with XMRV.

At 3pm Eastern time today (Monday, August 23) the NIH, FDA and CDC will hold a joint telebriefing for the press to discuss an XMRV paper that the Proceedings of the National Academy of Sciences (PLoS) is publishing. If the XMRV virus is finally confirmed after months of controversy, this will be a historic day.

On the call will be:

• Harvey Alter, M.D., Chief, Clinical Studies and Associate Director for Research, Department of Transfusion Medicine, NIH Clinical Center
• Shyh-Ching Lo, M.D., Ph.D., Director, Tissue Safety Laboratory Program, Division of Cellular and Gene Therapies and Division of Human Tissues, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration Food and Drug Administration
• Celia Witten, M.D., Ph.D., Director, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration
• Hira Nakhasi, Ph.D., Director, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Food and Drug Administration
• Steve Monroe, Ph.D., Director, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention

Will the public finally be told that XMRV is “real” and the nation’s blood supply is infected? If so, will the public finally wake up to the gravity of the situation with XMRV? Will mass panic break out if NIH confirms that people can catch the XMRV virus from a sneeze or kiss?

The question I keep asking myself is how did Addi and Cassi get XMRV? Since they are only six years old, they did not get it from having sex. Either I gave it to them (they were born with it) or they CONTRACTED it. I am almost certain that they CONTRACTED XMRV at around 3 years old when they first became sick with a mysterious “Mono” like syndrome and I took them to Stanford. Either way, it’s frightening because the twins contracted it from saliva (airborne) or I gave it to my unborn children!!!!!

One leading HIV-AIDS researcher I know, Dr. James Hildreth at Meharry Medical College in Nashville, has been funded by NIAID to look at the connection between the XMRV and cholesterol. Dr. Hildreth previously discovered that in order for HIV-AIDS to survive in the human body, it utilizes cholesterol and the Niemann Pick Type C gene. Does XMRV also utilize cholesterol and the Niemann Pick Type C gene that all people are born with to do it’s dirty work as well? I can’t help but wonder what role cholesterol plays in the XMRV virus, if any.

The question for me now is how do I deal with treating both conditions — a fatal progressive genetic cholesterol disease that is stealing my twins’ minds combined with a nasty retrovirus.

RareArtist.org – Rare Art Created by Rare People to Support Rare Disease Awareness

What a great idea — a new website to showcase Rare Art created by Rare People to support Rare Disease awareness.  The Kakkis Everylife Foundation has launched RareArtist.org for artists of all ages affected by a rare disease.

There are almost 7,000 rare diseases that affect more than 25 million Americans — many of them are children like Addi and Cassi who suffer from Niemann Pick Type C disease which causes childhood dementia and is fatal.

The EveryLife Art Contest was established to empower artists affected by Rare Diseases to express their unique struggle with a rare disease.  An art competition is being held and is open to all artists affected by a Rare Disease ages 5 and older.

Check out RareArtist.org today and upload your art!

Creating Hope Act 2010 Bill Would Extend Priority Review Voucher System To Rare Pediatric Diseases

Great news for the pediatric rare disease community came out late last week — rare disease advocates please get this out on your blogs!

Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) are supporting the bipartisan bill S. 3697, the “Creating Hope Act of 2010.” Nancy Goodman, Executive Director of Kids v Cancer, is the person leading the charge on S. 3697 and a priority review voucher system for pediatric rare diseases.

In 2009, Nancy lost her son Jacob to a rare pediatric cancer called medulloblastoma. She is an inspiration to all in the rare disease community!

The Creating Hope Act of 2010 builds upon the Food and Drug Administration Amendments Act of 2007, often called the “treat and trade” program, which established a priority review voucher program for drugs or biologics targeting neglected tropical diseases. At the time this bill was passed, rare childhood diseases were excluded.

The Creating Hope Act of 2010 will encourage the creation of new drugs for underserved children like Addi and Cassi who suffer from serious and life threatening medical conditions by providing a priority review voucher (PRV) as an incentive to pharmaceutical companies who develop drugs for rare pediatric diseases like Niemann Pick Type C.

This is exactly the type of novel incentive system I have been asking for that could fast track cyclodextrin research. For example, with a PRV system in place, I could get a company like Johnson and Johnson to actually take on Niemann Pick Type C disease research and help me make a cyclodextrin drug for Niemann Pick Type C kids.  In turn, Johnson and Johnson could receive a priority review voucher that gives them priority FDA review of another application that would otherwise be reviewed under FDA’s standard review clock.

This priority review voucher could be used for a blockbuster drug that a company would want want to bring to market and receiving priority review could mean millions of dollars to a Pharma or biotech company.  This is why they would be willing to invest in Niemann Pick Type C research and cyclodextrin and help our small community bring a potentially life saving compound to market for kids like Addi and Cassi.

Since I already have an orphan drug application filed and approved with the FDA, having a priority review voucher system in place potentially makes Niemann Pick Type C an attract investment risk by Pharmas or BioTechs.

Priority reviews vouchers for pediatric rare diseases are a  win-win for everyone!  We need to rally the rare disease community to fight for the passing of S. 3697, Creating Hope Act 2010 bill.

Below are some key provisions of the S. 3697, Creating Hope Act 2010 bill:

• Extension to pediatric rare diseases: This legislation includes rare pediatric disease within the scope of the program. This category encompasses any disease that is “rare” within the meaning of the Orphan Drug Act (affects less than 200,000 people, or the cost of development would exceed revenue) is recognized in the medical community as affecting a pediatric population and is a new drug that has not received FDA approval for an adult indication
• Closing a loophole: This legislation would prevent companies from receiving a voucher for tropical disease products that they already market in other countries. This change will ensure that the program rewards only innovative treatments
• Unlimited transferability of vouchers: A voucher may now be transferred unlimited times provided that the transferee, in each instance of transfer, notifies the FDA of the change in ownership. This change enables drug companies to maximize the value of the voucher in the marketplace
• Optional upfront priority review designation process: Under the current law, sponsors do not know whether their new drug application will qualify for a voucher until the time of FDA approval. The proposed legislation permits sponsors of both tropical disease drugs and rare pediatric disease drugs to seek a designation that the new drug would qualify for a voucher, should it be approved, even before they submit their new drug application.
• Adds Chagas disease to the list of neglected tropical diseases: Chagas disease is responsible for more deaths in Central and South America than every other parasite-borne disease, including malaria. Yet, despite its profound impact, research and development of new treatments is severely underfunded. The addition of Chagas to the list of eligible diseases fulfills the intent of the original authors.
• Reporting and marketing requirements: The Creating Hope Act requires that the sponsor submit a statement of good faith intent to market the eligible drug, as well as a report describing the demand and distribution of the ultimate product.

IND Application Filed With FDA To Bring Cyclodextrin Into The Brain To Treat Fatal Childhood Cholesterol Disease

After months and months of work and input by doctors and researchers, Dr. Caroline Hastings at Children’s Hospital Research Center Oakland filed our second Investigational New Drug application (IND) with the FDA on July 14, 2010.

The 200+ page IND filing details our request to deliver hydroxy-propel-beta-cyclodextrin (HPBCD or CYCLO) directly into Addi and Cassi’s central nervous system and ultimately their brains.

Addi and Cassi suffer from Niemann Pick Type C, a ultra rare and fatal genetic cholesterol disease that causes progressive neurological deterioration and has been callled the “childhood Alzheimer’s” as it causes dementia in children.

While only approximately 500 children in the world have double genetic defects on the Niemann Pick Type C gene, everyone is born with the NPC gene, and the gene regulates human cholesterol metabolism. Studying children like Addi and Cassi may lead to breakthroughs in more common diseases such as Alzheimer’s and heart disease where disrupted lipids and cholesterol are implicated.

For the past year, we have been treating Addi and Cassi with weekly intravenous infusions of cyclodextrin but we learned from leading blood brain barrier researchers that cyclodextrin does not readily cross from the bloodstream into the brain. However, when cyclodextrin is delivered directly into the brains of NPC animals (cats/mice), this compound is creating a remarkable effect and arresting the neurological condition.

Here is some data from the NIH and NINDS meeting last month from Dr. John Dietschy, one of world’s leading lipid and sterol researchers, at UT Southwestern. Dr. Dietschy’s data shows that cyclodextrin delivered into the central nervous system of NPC mice prevents neurodegeneration.

Mechanism of action of cyclodextrins in reversing cholesterol transport defects in Niemann-Pick type C disease
John M. Dietschy, M.D., Professor Department of Internal Medicine
University of Texas Southwestern Medical Center Dallas

Niemann-Pick type C (NPC) disease is one of a number of disorders in which the underlying metabolic defect is abnormal accumulation of either cholesterol (C) or cholesteryl esters (CEs). The severity of the disease in organs like liver, lung, and CNS is proportional to the amount of sterol that accumulates in that particular tissue, and interventions that prevent this accumulation prevent the disease. Administration of cyclodextrin (CYCLO) rapidly overcomes the C transport defect seen in NPC1 and NPC2 disease and allows the sterol to move to the cytosolic compartment of cells, to be transported to the liver, and ultimately to be excreted from the body as bile acid. The ED50 for this effect equals ~300 mg/kg in most organs. However, the value in kidney, which is only ~30 mg/kg, is much higher in the CNS. The ED50 value for the lung is infinitely high. This ED50 value for the CNS is much lower when the CYCLO is administered directly into the brain. The acute or continuous administration of cyclodextrin into the CNS normalizes cholesterol metabolism and prevents neurodegeneration. To bring about these changes, the particular CYCLO must interact with C, but it need not bring about solubilization into the bulk-water phase. After administration of appropriate doses at appropriate intervals, the pools of C in nearly every organ are maintained at normal levels and disease is prevented. Only in lung is the abnormal C metabolism resistant to CYCLO therapy. Consequently, whereas liver and CNS disease can be prevented, pulmonary disease progresses.

Besides thanking Dr. Caroline Hastings, Dr. Ron Browne and Karen Barca for helping get this second IND submitted, there are countless others to thank for their generous assistance and strategic guidance:

• NPC researcher Dr. Charles Vite worked closely with Dr. Steven Silber and the Johnson & Johnson team, who donated their time and critical expertise and knowledge to help conduct PK experiments on Addi and Cassi and the NPC cats
• Alzheimer’s biomarker expert (Dr. Kaj Blennow) conducted important CSF biomarker experiments and has also offered to continue testing the twins’ CSF when we get approval from the FDA to move forward
• Dr. Steve Walkley, Dr. John Dietschy, Dr. Jean Vance and Dr. David Begley provided critical research data on NPC animals in advance of publishing  which helped accelerate this process
• Rick Stratton and Dr. Lajos Szente, cyclodextrin experts, provided needed references and strategic advice
• Dr. Peter Penchev, the “godfather of NPC disease” for his support and strategic guidance
• Dr. Tony Yaksh at UCSD and Dr. Patti Dickson at UCLA provided relevant intratehcal and cyclodextrin data
• Dr. Joe Madsen in the department of neurosurgery at Children’s Boston and Dr. Peter Sun at CHRCO offered advice on the feasibility of delivering cyclodextrin into the CNS
• Dr. Emil Kakkis, founder of BioMarin and the Kakkis EveryLife Foundation provided toxicity and safety advice as well as overall encouragement
• Dr. Harrry Chugani at Children’s Hospital of Michigan provided cutting edge PET imaging which helped support our case to move in this new treatment direction

Countless others offered to read our protocol and provided a tip here and there which all adds up to a comprehensive FDA filing. We simply can’t thank all the people who donated their time to helping us make it this far.

The FDA apparently has 30 days to respond to our intrathecal cyclodextrin filing. We are praying that the FDA does not require unrealistic toxicity studies that we can’t afford or throws out some other hurdle that can’t be easily crossed. Addi and Cassi’s seizures are getting a lot worse and their disease is progressing with hypometabolsim spreading to many regions of their brains.

Intrathecal cyclodextrin treatment is our only hope to try and save their brains from dementia and save their lives.

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