RSRT scientific advisor, Rusty Gage has made yet another remarkable discovery.  He has found that brain cells are fraught with spontaneous mutations. In fact as many as 40% of neurons in the frontal cortex have mutations. Tom Insel, director of the National Institute of Mental Health comments on these findings in his latest blog post.

One Person Many Genomes

Dr. InselBy Thomas Insel on November 6, 2013

Of late, the word “government” has been frequently followed by dispiriting nouns like “shutdown,” “gridlock,” and “dysfunction.” By contrast, government-funded science has recently produced some high profile discoveries, although most news coverage of the work did not link the discoveries to government funding. One game changing finding worth highlighting from last week changes the way we think about genetics, the brain, and individual differences. First, a little background.

The world of genetics was shaken in 2007 by the discovery of “de novo” mutations associated with autism.1 These mutations were spontaneous changes in DNA sequence that were present in affected children but not in DNA from either parent’s blood cells. Apparently these mutations accumulated in the father’s sperm cells as these cells divided through multiple generations during his lifespan. Presumably older fathers had more of these spontaneous mutations. Indeed, epidemiological studies had reported that fathers over 40 were at higher risk for having children diagnosed with autism or schizophrenia.

Over the past 3 years, spontaneous mutations have been found to be much more common than we thought. And these mutations are not only transmitted from sperm but develop later in the fetus or even in rapidly dividing cells in adults. In fact, it appears that mutations are occurring all the time because DNA replication is surprisingly prone to errors. Many of these replication errors are of no consequence, but mutations in tumor suppressor genes appear to be the mechanism by which cancers arise in rapidly dividing cells of the gut or skin. These errors are called “somatic mutations” because they occur in select mature cells of the body. They are distinguished from “germline” mutations found in the stem cells of the embryo and retained in all cells of the body. Because of somatic mutations our bodies have multiple genomes: different mutations may be found in cells from gut, skin, or blood.

Somatic mutations have been a hot topic for cancer and stem cell biologists, but neuroscientists or psychiatric geneticists did not really worry about this problem because adult neurons do not divide. The genetics of mental illness has been based on DNA extracted from blood cells. Because we were not worried about the possibility of multiple genomes in a single person, we assumed that the genome of blood cells should tell us what we needed to know about DNA. Until recently, no one even worried enough about somatic mutations in brain to look for them.

Last year, Chris Walsh and his team at Harvard’s Children’s Hospital showed that rare neurodevelopmental disorders could result from somatic mutations found in a single area of the brain.2 Increased growth of one hemisphere of the brain was caused by a mutation in a growth gene called AKT3 only in cells from the enlarged hemisphere, not in the normally developing hemisphere and, importantly, not in blood cells.

Last week, groups led by Fred Gage of the Salk Institute and Ira Hall of the University of Virginia took the first careful look at DNA sequences in single neurons of a normal human frontal cortex.3 In a Science paper published online on Halloween, they reported the rather spooky finding that 41 percent of neurons had a major mutation, often unique to that cell. These mutations were not subtle: many involved deletions of more than a million bases of DNA and some involved duplications of chromosomes. Just as our bodies contain multiple genomes, it appears that our brains exhibit intense variation, perhaps greater than other tissues. How could this happen if neurons don’t divide? Actually, neurons during fetal development divide more rapidly than almost any other tissue known, with replication rates estimated at 100,000 divisions per minute from week 10 to week 24 of gestation when the brain surpasses 10 billion cells. It should therefore come as no surprise that somatic mutations are abundant in brain. Indeed, wouldn’t it be even more amazing if they did not occur?

Read in its entirety

It seems that cholesterol and the brain is becoming a hot field.  Following up on the RSRT-funded results of the Justice lab comes an intriguing (and unpublished) study highlighted by the Simons Foundation.

New autism gene plays key role in cholesterol synthesis

ImageMutations in a gene that plays a role in producing cholesterol in the body increase the risk for autism, pointing the way toward therapies for some people with the disorder. The research was presented in a poster Tuesday at the Autism Consortium’s 2013 Research Symposium.

Mutations in the gene, DHCR24, are known to result in a severe metabolic disease linked to cholesterol. The gene’s newly discovered role in autism suggests that statins, drugs that lower cholesterol levels, may treat symptoms of autism.

The potential is exciting,” says Timothy Yu, a neurologist at Massachusetts General Hospital and a researcher at the Broad Institute of the Massachusetts Institute of Technology and Harvard University in Cambridge, Massachusetts.

“If you can find these kids who are swimming around in an otherwise generic autism pool and figure out a way to treat them appropriately, then you actually have the possibility of therapy.”

The researchers screened 2,000 families that have at least one child with autism to identify rare recessive gene variants for the disorder. In one family, they found that a girl diagnosed with pervasive developmental disorder-not otherwise specified and two boys diagnosed with intellectual disability and autism had all inherited two copies of the mutation, one from each parent.

“The gene is involved with the cholesterol synthesis pathway, so it started us thinking about the pathway’s role in autism and intellectual disability,” says Elaine Lim, a graduate student in Mark Daly’s lab at Harvard who presented the research.

Read in its entirety

To profoundly impact a disorder with as many varied and debilitating symptoms as Rett Syndrome, it is likely that intervention must be directed toward the very root of the problem. There are several ways to do this: activate the silent back-up copy of the Rett gene; target modifier genes; explore gene therapy.

Today, we announce a study funded through the MECP2 Consortium suggesting that gene therapy may indeed provide a feasible approach to treat Rett Syndrome.

The work was led by Gail Mandel at Oregon Health and Sciences University in collaboration with Adrian Bird of the University of Edinburgh and Brian Kaspar of Nationwide Children’s Hospital.

Gail Mandel with lab members Dan Lioy and Saurabh Garg

Gail Mandel with lab members
Dan Lioy and Saurabh Garg

Adrian Bird and post-doc Hélène Cheval

Adrian Bird and post-doc
Hélène Cheval

In the past sixty days, four key papers have been published detailing research advances supported financially and intellectually by RSRT. Three of those papers are funded through the MECP2 Consortium, a unique alliance launched by RSRT in 2011 among three leading labs: Bird, Greenberg (Harvard) and Mandel. If you are a donor to RSRT, the accelerated research these projects represent is the result of your money at work.

We wish to express our gratitude to all of our generous supporters and the parent organizations that make this progress possible. Special thanks to our funding partners, the Rett Syndrome Research Trust UK and the Rett Syndrome Research & Treatment Foundation.

Below are some resources to help you understand today’s announcement.

Press Release [Spanish Translation] [German Translation]


Video interview with Dr. Mandel & lab members

In contrast to the leadership of most organizations we yearn for the day when RSRT is no longer in business – that will mean an end to Rett. Until that day comes we will continue to invest in high quality science. In the first half of 2013 RSRT has committed $1.7 million to new projects that range from basic science to clinical trials. We invite you to learn about our investments, which our donors have made possible. As always we welcome your questions and feedback.

Copaxone Clinical Trials

There is a multitude of data suggesting that mice models of Rett have low levels of a neurotrophic factor called BDNF (brain derived neurotrophic factor). BDNF is a very important and complex protein that is implicated in a variety of disorders. Increasing BDNF in the Rett mice models, either genetically or pharmacologically is beneficial. An FDA approved drug for multiple sclerosis called copaxone (or Glatiramer Acetate) is known for increasing BDNF and therefore of interest in treating Rett.

RSRT has committed to funding an open label study of copaxone in two centers, the Tri-State Rett Syndrome Center at Children’s Hospital at Montefiore in the Bronx, under the supervision of Dr. Sasha Djukic, and at Sheba Medical Center in Ramat Gan in Israel under the supervision of Dr. Bruria Ben Zeev. Each center will give copaxone to ten individuals for 6 months. Below is a comparison of the two studies. 

Sasha Djukic, M.D., Ph.D.

Sasha Djukic, M.D., Ph.D.

Bruria Ben Zeev, M.D.

Bruria Ben Zeev, M.D.

USA Israel
Title Pharmacological treatment of Rett Syndrome with Glatiramer Acetate (Copaxone) An open-label exploratory study to investigate the treatment effect of glatiramer acetate (Copaxone) on girls with Rett Syndrome
Principal Investigator Aleksandra Djukic, MD, PhD Bruria Ben Zeev, MD
Location Children’s Hospital at Montefiore, Bronx Sheba Medical Center, Ramat Gan, Israel
Objectives Primary: gaitSecondary: cognition, autonomic function, EEG, quality of life Primary: EEG improvementSecondary: autonomic function, general behavior, communication, hand stereotyping, feeding, gastrointestinal
Study Size 10 girls – 10 yrs old and up 10 girls – 6 to 15 yrs old
Dose (injections) Ramp up to 20 mg per day Ramp up to 20 mg per day
Length of study 6 months 6 months

While copaxone is not going to cure Rett Syndrome we hope that by increasing BDNF we will see improvements in symptoms. The trials are currently recruiting.

The X Factor

If you’ve been following RSRT’s activities then you know that one of the strategies we are pursuing is reactivation of the silent MECP2. We are adding Michael Green of UMass to our existing portfolio of labs who are working in this space.

Michael Green, M.D., Ph.D.

Michael Green, M.D., Ph.D.

Dr. Green is taking a somewhat unconventional approach as he is attempting to reactivate the entire X chromosome and not just MECP2. His work first came to RSRT’s attention in 2009. We learned that he was conducting a screen to identify genes that control X chromosome inactivation (XCI). As his work matured over the next few years he did indeed identify factors that control XCI, some of which belong to molecular pathways for which there are drugs. These drugs can now be tested in culture and in vivo in the Rett mice models.

Recently a paper from a colleague of Michael Green’s, Jeanne Lawrence, received enormous attention for doing the opposite of what Dr. Green proposes – inactivating the extra copy of chromosome 21 that causes Downs Syndrome (DS). While this work is not ready for prime time it is an exciting new avenue that could eventually make treatment for DS a reality.

Continuing our X Factor focus we awarded an additional grant to Jeannie Lee of Harvard University. She is currently funded for a drug screen to reactivate MECP2. While the goal of the new award is the same – activate MECP2 – how she proposes to accomplish it is completely novel.

Jeannie Lee, Ph.D. at an RSRT meeting in November

Jeannie Lee, Ph.D. at an
RSRT meeting in November

The hypothesis of Dr. Lee’s approach rests on an observation that a group of proteins called Polycomb complexes working in concert with a certain type of RNA, called noncoding RNA (lncRNA) are relevant for keeping genes silent on the inactive X.

Dr. Lee’s therapeutic strategy is to awaken the MECP2 gene by disrupting the binding that occurs between the lncRNA and the Polycomb complexes.

While the work is early stage, if Dr. Lee’s hypothesis proves correct this approach would be attractive.

Ketamine – the follow up

Last October David Katz of Case Western Reserve University published a paper showing that certain physiological symptoms in the Rett mice normalized after treatment with an aesthetic called ketamine. With RSRT funding Dr. Katz will continue to pursue this line of exploration with additional drugs that work in the same pathway but have less side effects. He will also attempt combination therapies with various drugs.

Below is a video interview with Dr. Katz that was posted earlier this year.

Gene Therapy for the MECP2 Duplication Syndrome
Kevin Foust (left) and Brian Kaspar at a recent RSRT meeting.

Kevin Foust (left) and Brian Kaspar
at a recent RSRT meeting.

The final award was granted to Kevin Foust of Ohio State University. Dr. Foust has been working with Brian Kaspar and Gail Mandel on gene therapy approaches to treat Rett Syndrome. This award builds on that work by extending a gene therapy approach to the MECP2 Duplication Syndrome. Dr. Foust will deliver RNA interference (RNAi), a biological process in which RNA inhibits protein production) via a vector in duplication syndrome mice.

If the data is encouraging this work would form the basis for a therapeutic approach to treating patients.

This work is being funded via the MECP2 Duplication Syndrome Fund at RSRT and directly supported through the efforts of the duplication families.

We look forward to bringing you updates on these and all of our projects.  Once again we thank all of our supporters – this is your money at work for our girls.

Monica Justice, Ph.D.

Monica Justice, Ph.D.

Rett Syndrome is a spectrum disorder with a broad range of symptom severity. Some girls can run, have some use of their hands and can speak in short sentences while others cannot even sit or manage to hold their head up. One reason for this variation is the child’s own unique genetic make-up  – in other words, variations in other genes that impact the severity of the Rett mutation. Identification of modifier genes has therefore been a critical component of RSRT’s research program as the modifiers may provide alternate pathways to target.

This hypothesis has now been supported in a major study that could lead to treatments for girls and women with Rett Syndrome.  Today the journal Nature Genetics publishes data on the first reported modifier, called Sqle, an enzyme involved in the cholesterol pathway.

Monica Justice, Ph.D and graduate student Christie Buchovecky from Baylor College of Medicine.

Monica Justice, Ph.D and graduate student Christie Buchovecky from Baylor College of Medicine.

The research was undertaken by Monica Justice, PhD, of Baylor College of Medicine, with a $1.5 million investment from RSRT.  Dr. Justice tested statins (cholesterol-lowering drugs) on Rett mice models with encouraging results.  A human clinical trial is now being planned.

RSRT is committed to seeing this project through to completion as many more modifiers, and therefore druggable pathways,  are likely to be found.  We thank all of our generous supporters and parent organizations who make this important work possible, in particular our funding partners, Rett Syndrome Research Trust UK and the Rett Syndrome Research & Treatment Foundation.

Justice-and-mice

Below are some resources to help you understand today’s announcement.

Press Release
[Spanish Translation]
[Italian Translation]

A paper just out in PLOS Biology is unable to confirm that the drug Ataluren is able to read through premature stop codons (nonsense mutations, for example 255X, 168X). The drug is already in clinical trials for Cystic Fibrosis and Duchenne’s  muscular dystrophy.   The new data highlights not only the difficulties in drug development and the importance of rigorous clinical trials but also the need for independent confirmation of data.  This drug is currently being tested in a mouse model of Rett Syndrome with a 168X mutation.

Drug Mechanism Questioned
A study fails to confirm that the small molecule PTC124, in development for multiple genetic disorders, aids in read-through of premature stop codons.
By Kate Yandell

Assays using glowing luciferase from fireflies play a controversial role in PTC124's history.

Assays using glowing luciferase from fireflies play a controversial role in PTC124’s history.

An in vitro study of PTC124, a drug in clinical trials for the treatment of cystic fibrosis and several other genetic disorders, has some scientists wondering whether the molecule works the way its developers say it does.

PTC124 is intended to treat disorders, including some cases of cystic fibrosis and Duchenne muscular dystrophy, that stem from mutations that cause stop codons to erroneously appear in critical gene transcripts, thereby inhibiting translation of vital proteins. The new study, published today (June 25) in PLOS Biology, demonstrates that PTC124 does not promote read-through of such premature stop codons, or “nonsense” mutations, in several reporter assays done using a human cell line.

“The paper is well designed and carefully executed, and the dataset is unambiguous,” said Bryan Roth, a professor of pharmacology at the University of North Carolina at Chapel Hill who was not involved in the work, in an email to The Scientist. “I think these are important findings which cast doubt on the role of nonsense suppression on the actions of PTC124.”

“From a basic mechanistic standpoint, it doesn’t look like [PTC124 is causing] translational read-through, certainly in our assays,” said Stuart McElroy, a molecular pharmacologist at the University of Dundee in Scotland and an author of the paper.

But representatives from PTC Therapeutics, the New Jersey biotech company that is developing the drug, said that it has produced strong evidence that PTC124, also called ataluren, does encourage the translation of complete proteins despite the nonsense mutations. “Numerous independent laboratories have provided confirmation of our results, demonstrating ataluren’s read-through activity in studies using reporters as well as multiple animal and cell-based nonsense mutation disease models,” the company said in an emailed response to questions sent by The Scientist.

Read More …

Press Release Announces Tim’s Hire

Dear Friends,

Tim-and-Eleanor-2A year and a half ago my wife, Rachel, and I received the worst phone call of our lives—it was the Children’s Hospital of Pennsylvania informing us that our beautiful, bright-eyed, giggling two-and-a-half year old daughter, Eleanor, had tested positive for the MECP2 mutation that causes Rett Syndrome.  We were simply devastated and didn’t know what to do or where to turn.  The ensuing months were the hardest of our lives.  Our dreams and hopes for our only child had been crushed.  We watched helplessly as Eleanor stopped scooting on her rear end, as she had been doing, and developed a repetitive hand motion and other symptoms.

Several months later, Rachel found the RSRT website.  We made a call and RSRT’s co-founder and executive director, Monica Coenraads, answered the phone.  We soon learned that we were not alone in our sadness and that there was a community of wonderful, supportive parents, grandparents, family members, and friends of families who have been impacted by Rett Syndrome.  And even more exciting, we learned that there was hope for a cure for Rett.  In fact, it was clear that there was a good deal more than hope—Rett symptoms had been reversed in an animal model, and very promising scientific progress was being made, much of it encouraged and supported by RSRT.

Monica and I continued to correspond.  I was seeking her advice and thoughts about Eleanor’s diagnosis, and I was trying to understand the research and science.  Monica began seeking my advice about fundraising and public relations when she learned that I headed the development office of the Woodrow Wilson Foundation in Princeton, New Jersey, and before that had served as director of development at Columbia University’s Teachers College.  It may have dawned on Monica and me at the same time that there was a fit here—that I cared deeply and personally about the work that RSRT was doing and that I had nearly 20 years of experience that could help grow RSRT and its impact on the lives of girls and women with Rett.

Tim-and-EleanorThe rest, to use the cliché, is history.  My first official day as a Program Director at RSRT was June 17.  Under Monica’s direction, I’m responsible for fundraising, public relations, and strategic thinking about the organization.  I couldn’t be more excited.  So many people, Monica foremost among them, have worked so hard and contributed so much to making RSRT the respected force that it is and to building the cumulative scientific knowledge that will lead to a cure.  I’m honored and humbled to join this team.  Frankly, I never imagined that I would be able to put my knowledge and skills to use for something so important to me.

I’ve gone on longer than I intended, but I have one further thought.  I’ve been thinking lately about President Kennedy’s 1961 speech to Congress in which he announce the dramatic and ambitious goal of sending an American to the Moon before the end of the decade.  It took a huge team effort, conviction and confidence in a very clear mission, ample resources, and leadership, for the goal to be met.  I think RSRT’s goal is not unlike President Kennedy’s in its ambition, its clarity, its importance, and its attainability.  I also believe that all of us working together are the team that will get us to the moon.  And, like building a rocket, a cure depends on cumulative knowledge that is the sum of its parts.  The rocket needs its nose cone, its fuel tank, its electronics, its landing pads, and other components to meet the goal.  Research is like this too.  All the parts have to work together.  It is cumulative knowledge that will get us there.

Tim-and-Eleanor-3I am tremendously grateful to Monica, to the RSRT Board, and to all of you who contribute your time, energy, and resources to RSRT for your confidence in me.  I promise Eleanor and all of our daughters that I will do my best in everything I do for RSRT.  I will need your help, advice, and counsel—most of you know RSRT and all of its accomplishments and the Rett community at large far better than I do—so I hope I can call on you.  Please don’t hesitate to contact me any time.  My office line is 609-309-5676; my cell is 609-815-5102; and my email is tim@rsrt.org.  I look forward to meeting you.

Best,

Tim Freeman

adrian-bird

Adrian Bird (left) and Matt Lyst
University of Edinburgh

michael-greenberg

Michael Greenberg (right) and Dan Ebert
Harvard Medical School

It stands to reason that in our battle to cure Rett Syndrome it would be of great benefit to understand the function of the “Rett protein”, MeCP2. Towards this end RSRT launched the MECP2 Consortium in 2011, a unique $1.8 MM collaboration between three distinguished scientists, Adrian Bird, Michael Greenberg, Gail Mandel.  On June 16th the first two publications from this collaborative effort are published in Nature Neuroscience and Nature. Together these papers provide further clarification of the elusive function of the MeCP2 protein and how mutations within it contribute to Rett.

We thank Kathy and Tony Schoener whose visionary $1 MM gift made the Consortium possible. We thank all of our donors and parent organizations worldwide who support us, in particular our funding partners Rett Syndrome Research Trust UK and the Rett Syndrome Research & Treatment Foundation.

We are providing a variety of resources to help you understand the progress being reported today.

Press release

Animation of Nature Neuroscience Paper (courtesy of Jeff Canavan)

Chinese Translation

Interview with Matt Lyst, post-doc in Bird lab

Interview with Michael Greenberg and Dan Ebert,
post-doc in Greenberg lab

We break down a few interesting results recently published.

Multiple mutations on MeCP2

In most cases of Rett syndrome, one mutation occurs on (a single copy of) the MeCP2 gene. But, rarely, multiple mutations occur on the same copy. Researchers from the University of Alabama at Birmingham characterized the largest group of individuals to date, 15 of them, who have more than one mutation. (The girls were participating in the Rett Syndrome Natural History Study, which aims to gather detailed historical and physical examination data on a large cohort of females with Rett — of which there are now more than 800.)

In contrast to two previous case studies suggesting that girls with more than one MeCP2 tend to have more severe disease, the new study found that participants with multiple mutations assessed using two quantitative measures — the Clinical Severity Scale and the motor behavioral analysis — showed no difference from those individuals with single, similar mutations. The findings appear in the American Journal of Medical Genetics Part A.

Other factors, including the individual mutations themselves or how much of the mutated gene is inactivated as part of normal development, can worsen symptoms, the authors suggest. Future drug therapies that account for a person’s genetics should consider this small group of individuals, the authors add.

Rett Syndrome and epilepsy

Seizures affect 50% to 90% of individuals with Rett syndrome. According to a recent review in Pediatric Neurology by Alison Dolce and her colleagues at Johns Hopkins Hospital in Baltimore, Maryland:

  1. It’s unclear whether earlier onset of seizures signals a poorer overall prognosis.
  2. EEG, or electroencephalography, an indirect measure of brain activity, is an important diagnostic tool in children with Rett syndrome because it allows clinicians to identify true seizures — as opposed to symptoms, ranging from hyperventilation or motor abnormalities, that are often mistaken for seizures. From 2 to 4 years of age and beyond, all girls with Rett syndrome develop abnormal EEGs, the authors write.
  3. There are few studies assessing anticonvulsant therapies in Rett, and many of them are short-term and involve only a small number of participants. “At our centers, we have circumstantial evidence of good responses to levetiracetam, lamotrigine, and topiramate,” the authors write. Although the clinicians also use valproate, the side effects can be problematic. In general, many children with Rett require more than one medicine.
  4. It’s still difficult to predict which patients will tend to develop seizures early and also whose seizures will be easier to treat.
  5. According to the authors, physicians should begin to consider the ketogenic diet and vagal nerve stimulation earlier in the clinical course of Rett, because these treatments “might be helpful.”

More on MeCP2 mechanisms

MeCP2 protein has several defined parts that researchers are studying. The methyl-CpG-binding domain or MBD, for example, binds to DNA in studies conducted in vitro and is thought of as crucial for the protein’s function of turning genes on or off, or altering the way DNA is stored in a cell. Given that the interactions between MeCP2 and DNA are difficult to mimic in a dish, a team of Canadian scientists wanted to see what would happen to the interaction in a mouse whose front end of the protein was deleted. The Mecp2tm1.1Jae model, commonly used in studies of Rett syndrome, is missing its first 116 amino acids—which include the 48 amino acids that make up the MBD. (What’s more, MeCP2 mutations in people with Rett occur in this region, such as R106W, R1333C, P152R, F155S and T158M.)

In the study, mutant mice still had MeCP2 in their tissues but only about half as much as healthy mice did. Although the mutated MeCP2 still bound to DNA and chromatin, the interactions were weaker and less specific for methylated DNA. In addition, although the ‘nuclear localization signal’ region of the mutated protein was still intact, protein was less able to move from the cytoplasm to the nucleus, where it can influence the production of other proteins. The paper is published in the May issue of Nucleic Acids Research.

News from the Fragile X community highlights the challenges of clinical trials.

Below is an article from the New York Times written by Andrew Pollack.

FRAGILE-articleLarge

Holly Usrey-Roos will never forget when her son, Parker, then 10, accidentally broke a drinking glass and said, “I’m sorry, Mom. I love you.”

It was the first time she had ever heard her son say he loved her — or say much of anything for that matter. Parker, now 14, has fragile X syndrome, which causes intellectual disability and autistic behavior.

Ms. Usrey-Roos is certain that Parker’s new verbal ability resulted from an experimental drug he was taking in a clinical trial, and has continued to take for three years since then. She said she no longer had to wear sweaters to cover up the bruises on her arms she used to get from Parker hitting or biting her.

Now, however, the drug is being taken away. It has not met the goals set for it in clinical trials testing it as a treatment for either autism or fragile X syndrome. And Seaside Therapeutics, the company developing it, is running out of money and says it can no longer afford to supply the drug to former participants in its trials.

The setback is a blow in the effort to treat autism since the drug, arbaclofen, was one of the furthest along in clinical trials. And the company’s decision has caused both heartbreak and outrage among some parents.

“I waited 10 and a half years for him to tell me he loved me,” said Ms. Usrey-Roos, who lives in Canton, Ill. “With fragile X, you’re like living in a box and someone is holding the lid down. The medication opened the lid and let Parker out.”

“I don’t want to go back to the way life was,” she added.

The situation raises questions about what, if anything, drug companies owe to patients participating in their clinical trials. It also points out the difficulties in developing drugs to treat autism and fragile X syndrome. If the drug worked so well in some patients, why has it not succeeded so far in clinical trials?

Read the full article …

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