Not directly FX related but it has potential.

Gene therapy makes major stride in ‘Lorenzo’s Oil’ disease

In the third gene-therapy success of recent weeks, French researchers have arrested the progression of the rare and fatal degenerative disorder adrenoleukodystrophy, which was at the heart of the popular movie “Lorenzo’s Oil.” The disease has stabilized in two boys who were 7 years old when the therapy was performed two years ago, the team reported today in the journal Science.

“This is a disease that never, ever stabilizes” on its own, said Dr. Katherine A. High of the Children’s Hospital of Philadelphia, who was not involved in the research. “The fact that they were able to achieve that means they are getting a therapeutic effect.”

This is the fifth disease for which gene therapy has been shown to be beneficial, said Dr. Theodore Friedmann of UC San Diego, who was also not involved. “That’s a major achievement for a field that has been in the clinic for only 18 or 19 years. . . . This is a new form of medicine and deserves to be seen as such.”

The French team has already treated a third boy who has the disease. Although results are not yet available in that case, the team plans to expand the trial to others, including older men with a milder form of the disease.

Adrenoleukodystrophy, commonly known as ALD, is identified in about 120 young boys in the U.S. each year. Those born with the defective ALD gene appear to be normal until about age 5, “when a really catastrophic process of progressive, relentless demyelination [of the brain] sets in that leaves them vegetative or dead within one to two years,” said Dr. Florian Eichler of Massachusetts General Hospital, an expert in the disease. “This is as bad as neurological disorders get.”

If the disorder is identified before brain deterioration begins, the concoction known as Lorenzo’s oil — a mixture of fats from olive and rapeseed oils that purportedly reduces abnormally high levels of damaging long-chain fatty acids in the brain — can delay the disease’s progress somewhat.

Once deterioration begins, however, the only option has been a bone marrow transplant. For the few children who have a closely matched sibling, the procedure can arrest progression. A transplant from a less closely matched donor can help, but can also have severe side effects. Some patients, for example, must use a wheelchair as a result of the procedure.

The new research was conducted by a team headed by Drs. Nathalie Cartier and Patrick Aubourg of Paris Descartes University, who have been involved in previous successful studies of severe combined immunodeficiency disease.

They took the healthy form of the ALD gene and inserted it into HIV — the AIDS virus — that had been “defanged” so that it could no longer cause disease. HIV, from the lentivirus family, has been of great interest to gene therapists because it can insert genes into cells that are not actively dividing. Previous viruses used as delivery systems have only been able to insert genes into cells that are dividing.

The HIV delivery system may also be safer. Mouse retroviruses that have been used in previous studies of gene therapy can activate genes near where the added gene is inserted into the chromosome, potentially creating problems. That may be why a gene-therapy treatment for X-linked severe combined immunodeficiency, or SCID, caused some cases of leukemia. Lentiviruses are much less likely to turn on unwanted genes.

Despite years of research, this is the first time that a lentivirus has been used in a human trial. Aubourg and his colleagues chose it because it introduces the desired gene into a higher proportion of cells.

The French team isolated bone-marrow stem cells from the two boys, then used the virus to introduce the healthy ALD gene. They then did the equivalent of a bone-marrow transplant, destroying the boys’ marrow and introducing the modified cells, which proliferate to form new marrow. About 15% of the cells began producing the desired protein, and production has persisted for the two years of follow-up.

Fifteen percent may not seem like much, but “it is a level that would be therapeutic for a variety of other diseases, like sickle cell disease,” said Dr. Donald Kohn, a gene-therapy researcher at UCLA.

He noted that the first successful treatment for SCID in Milan got production of the desired gene in only “1% of cells at best.”

The effects on the disease were about the same as those from a successful bone-marrow transplant using closely matched cells, Aubourg noted.

“That’s good news because many patients don’t have access to bone-marrow transplants [that are good matches], and it is not an innocuous procedure,” Friedmann said.

The team documented its success in arresting the disease in a variety of ways, and was able to demonstrate that the procedure was safe.

In the last two weeks, researchers have reported using gene therapy to treat an eye disease called Leber’s congenital amaurosis and to rejuvenate human lungs that would otherwise be unfit for transplantation — although treated lungs have not yet been transplanted into humans. Two forms of SCID had previously been cured, and now ALD.

Gene therapy “has crossed a threshold, scientifically and medically, and also in credibility,” Friedmann said. These studies “are not hype; they are not hyperbole. They really are providing treatment for sick people.”

Clinical Tests Begin on Medication to Correct Fragile X Defect

See here for the official release.

Clinical Tests Begin on Medication to Correct Fragile X Defect

NIH-supported scientists at Seaside Therapeutics in Cambridge, Mass., are beginning a clinical trial of a potential medication designed to correct a central neurochemical defect underlying Fragile X syndrome, the most common inherited cause of intellectual disability. There has to date been no medication that could alter the disorder’s neurologic abnormalities. The study will evaluate safety, tolerability, and optimal dosage in healthy volunteers.

The work is the outcome of basic research that traced how an error in the fragile X mental retardation gene (FMR1) leads to changes in brain connections, called synapses. The changes in turn appear to be the mechanism for learning deficits in Fragile X syndrome. The new trial tests Seaside Therapeutics’ novel compound, STX107, that selectively and potently targets the synaptic defect.

Thomas R. Insel, M.D., director of the National Institute of Mental Health, said, “This project is the culmination of years of fundamental research, first identifying the genetic mutation and later deciphering the biochemical consequences of this mutation. Now, with the initiation of this first clinical study, we move one step closer to understanding how this novel candidate may play a critical role in improving the lives of individuals with Fragile X Syndrome.”

Randall Carpenter, M.D., president and chief executive officer of Seaside Therapeutics, and Mark Bear, Ph.D., Seaside’s scientific founder, are leading the research. Dr. Bear is a Howard Hughes Medical Institute investigator and a professor of neuroscience at the Massachusetts Institute of Technology, Cambridge, Mass.

The National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Neurological Disorders and Stroke (NINDS) have provided grant support. Private foundations providing funding include the advocacy groups Autism Speaks and FRAXA Research Foundation.

Fragile X syndrome is the most common inherited cause of intellectual disability, affecting an estimated 1 in 4,000 males and 1 in 6,000 females.

The syndrome causes a range of developmental problems, including learning disabilities and cognitive impairment. People with Fragile X syndrome may have anxiety and attention deficit hyperactivity disorder. About one-third of males with Fragile X syndrome also have autism or autistic-like behavior that affects communication and social interaction. Usually, males, who have only a single X chromosome, are more severely affected than females.

People with Fragile X have DNA mutations in the FMR1 gene that, in effect, turn off the gene. Research in recent years by Dr. Bear and colleagues has identified the molecular consequences of this silencing of FMR1. Normally, the protein product of the FMR1 gene acts to dampen the synthesis of proteins at synapses that are stimulated via a specific class of receptors on brain cell — metabotropic glutamate receptors (mGluRs). Without the brake provided by FMR protein, synaptic protein synthesis is excessive and connections do not develop normally.

This basic research provided the basis on which to develop medications that could correct the defect.

The current study will focus on a compound, designated STX107, that selectively inhibits one type of mGluR receptor, mGluR5. Evidence in mice with Fragile X-like symptoms suggests that reducing levels of mGluR5 can restore normal synaptic protein synthesis and improve function.

The initial phase 1 study of STX107 will involve healthy volunteers. If results suggest that the medication is safe and tolerable, the study will progress to a phase 2 test of dosage and efficacy in adults with Fragile X syndrome. If STX107 shows promise in adults, the compound will be assessed for pediatric safety (with funding from the Best Pharmaceuticals for Children Act [] through NICHD) prior to initiating clinical trials in children.

For more information on clinical trials related to Fragile X syndrome, go to

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at

NINDS ( is the nation’s primary supporter of biomedical research on the brain and nervous system.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

The American Express Member’s Project debacle.

This is a very hot topic right now, you can read great pieces here and here.  I just wanted to toss in my two cents. 

I feel incredibly disappointed by the actions of American Express.  I understand that tucked away in their FAQs they explained that voting was only going to matter for the final round but that is absolutely not how the project was presented publicly.  “Your Ideas. Your Decision. Our Money,” seems pretty clear. 

Our community worked so hard to spread the word and get out votes.  We funneled so many people onto the American Express website to vote.  Against the odds we were able to generate enough votes to put Cure Fragile X at the #5 spot out of 1,200 projects, only to be told it wasn’t good enough.  No one on the advisory board knew what it was, there wasn’t enough “buzz.”  I have to say any doctor on that board who didn’t know what it was and didn’t even bother to do a damned Google search, isn’t worth whatever he is being paid.

I’ll admit, Fragile X is not a “sexy” disorder.  It f*cking sucks, to put it bluntly.  But we all work so hard to help our kids day in and day out while we hope that some day it will get better for them and for us.   To have a giant corporation wave this under our noses only to snatch it away after all the hard work we put into getting out the vote was like a giant middle finger from American Express and I, for one, will never forget it.

If anyone feels like contacting the company I suggest one of these executive officers.  There are two variations for each e-mail because some people at the company have a middle initial in their address and some do not.  I’m not certain these will work but it may be worth trying 😉

Chairman and Chief Executive Officer


Executive Vice President and Chief Financial Officer


Vice Chairman, American Express Company and Group CEO, Business-to-Business


President, American Express Company


National Fragile X Awareness Day

I am the poster child for the necessity of this day.  Although Fragile X has been in my family for many generations and showed its face for the first time in full mutation form in my generation, I was completely unaware of its existence until my own son was unexpectedly diagnosed. 


Today is a day for spreading the word so that more families are spared the shock of having this disorder explode unexpectedly in their lives.  Today is a day for spreading the word so that more families get the diagnosis and the help that they need when their child is still young.  No family should have to search for years for an answer to the symptoms their child exhibits.


I know most people who are reading this know someone, or have a child, with Fragile X and so already understand the importance of awareness.  We are the soldiers in this battle. There are many people who are making decisions on research and brainstorming ideas to raise awareness but it is those of us who are living this day in and day out who can take direct concrete action to raise awareness everyday.  You don’t need to orchestrate a fundraiser.  You don’t need to take part in an article for your local paper or a national magazine.  You can just talk about your child to everyone who will listen.  Tell the waitress, tell the person sitting next to you on the train, tell your co-workers…write about it on your blog!  Buy these cards and stick them in every letter or bill that you mail.  



Every little bit helps, the more people we reach, the more families we help.


And if you have some money to spare, donate.  Every little bit helps.

Effective ADHD Treatment Found for FX

Very interesting!

Effective ADHD Treatment Found for Children with Fragile X Syndrome

ScienceDaily (Feb. 21, 2008) — Fragile X syndrome (FXS) is the most common hereditary form of mental retardation. Many children with FXS also suffer from attention deficit and/or hyperactivity disorder (ADHD), which complicates social relationships at home and at school. Although stimulant medication such as Ritalin® is often successfully used to treat children with ADHD, studies have shown that while it is effective in children with mental retardation, it also causes side effects such as increased irritability, decreased verbalization and social withdrawal.

A previous study showed that L-acetyl carnitine (LAC), a form of the amino acid carnitine, significantly reduced hyperactive behavior in FXS boys with ADHD who were treated with it for one year without causing adverse side effects. The same authors have now conducted a randomized, double-blind, placebo-controlled multicenter study to determine the effectiveness of LAC in a larger group.

Led by M. Giulia Torrioli and Giovanni Neri of the Università Cattolica in Rome, the study involved 51 boys between 6 and 12 years old with FXS and ADHD who were treated in one of eight centers in Italy, France and Spain. Each patient followed the treatment for 12 months, which involved 500 milligrams of LAC or a placebo given twice daily. Patients were evaluated by an interdisciplinary team of child neuropsychiatrists and psychologists at the start of the study, after one month, six months and 12 months. The effects of the drug and placebo were evaluated using a set of neuropsychological tests to assess behavior.

Those treated with LAC demonstrated reduced hyperactive behavior and increased attention. No side effects were exhibited, confirming that LAC is a safe alternative to stimulants. The patients treated with the placebo also showed reduced hyperactive behavior, although not nearly to the extent as the LAC-treated patients. The patients treated with LAC also had significantly improved social ability compared to the placebo-treated group. Both groups took intelligence tests, but LAC did not improve overall intellectual functioning.

“We propose that LAC be recommended as a treatment of ADHD in FXS children,” conclude the authors, “since it effectively reduces hyperactive behavior and improves social abilities without adverse side effects.” They also suggest that these results may be applicable to children with autism, who also do not easily tolerate stimulants.