This is an example of media emotional manipulation. Reporters know, or should know, that in order for research to be meaningful there are rigorous rules that must be met. Until the studies are complete, the drug being tested cannot be ruled beneficial or even safe. Most studies do not produce triumphant "cures" heralded by the media. But time and again the media trot out individual stories of patients who do not meet research criteria, implying that some thing should be done. Something is being done. It is called science, it takes time, and it should not be a dramatic media orchestrated event.
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From what I can tell from the photos, none of these boys has contractures, very surprising. It makes me wonder whether they were diagnosed on clinical signs or genetic testing, and where. Duchenne's is a continuum--from severe to milder Beckers. Also, neurologists at even the top childrens' hospitals in the country do not understand the many complex MDs as much as we need them to--the basic science. My own son was diagnosed with Duchennes, then Beckers, then Emery-Dreyfus, then Limb-Girdle, then Calpain 3, an LG variant,.... all at the top MD centers at major East Coast research universities where we lived. Change neruologists, and your diagnosis is likely to change. Pursue a diagnosis, of course, but don't assume it is correct; a single form has hundreds of unique mutations, and dystrophin is absent or reduced in many forms. My advice, since treatment is stuck in hundreds-years-old approaches and no money is being spent on research to actually make life better for these patients (it doesn't pay): focus on making your child as happy and independent as possible, and navigating the many changes in mobility to come. It was 1985 that the gene for Duchenne's was discovered and victory was declared; the trials described here have been "coming" for about for 20 yrs. Live your lives; if a cure comes and our children are still alive to benefit, wonderful, but the complexity of these diseases suggests banking on a cure is a recipe for more disappointment. Hope without expectation.
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Great Information. Being a Parent everyone should take extra care of their children facing this situations or health issue.
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As a parent of a child who was afflicted with Duchenne muscular dystrophy, a biomedical researcher and a bioethicist, I have a unique perspective on this matter. Clinical trials with gene therapy are incredibly challenging and must be done with great caution and rigorous controls. The field of gene therapy suffered a major setback in 1999 when Jesse Gelsinger, a teenager who volunteered for one of the earliest gene therapy trials died from the treatment. We cannot repeat this mistake by not properly screening candidates for suitability for this therapy, lest we once again set back the field of gene therapy and its potential to create miraculous cures.
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Chosen children will be lucky guinea pigs. Once this therapy is FDA-approved and on the market, it will only be affordable to the rich.
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I will take the label of cruel, however I must ask - if the parents knew that they could have this issue after their first kid, why did they insist upon having even more kids?
This article seems to be more about garnering sympathy for the parents than the suffering that the children are enduring because of their parents.
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@Tom
Symptoms do not develop until they are a few years old, so often the second son is born before the first is diagnosed.
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@Tom Magic is afoot. As long as a commenter can figure out a way to blame someone, the problem will never happen to him or her. Rejecting the import of an article because someone mentioned in it might receive "sympathy" is a related technique.
Those who permit other people's pain to touch them can feel a dizzying combination of fear and an urge to help. Distancing oneself neatly avoids both fear and effort.
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I feel deeply for these parents and children. We are so lucky that our son with cystic fibrosis, a similarly devastating, degenerative, genetic disease, will benefit from brand new, highly effective treatments exploding into use. I wish your families the same hope.
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We have gone from no hope to some hope for some kids. Devastating for those families whose sons do not qualify. But this is how science works. Not perfect. I feel so deeply for those families, having seen so many young men die of DMD. But if trials are not done properly, those treatments will never see the light of day. No good or hopeful answers for those who wait. My heart breaks.
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Why does this article speak only of boys. I am 79 years old and from the ages of 6 to 60 I had a best girlfriend with MD. We were all amazed that she lived that long. In our teen years I pushed her wheel chair and traveled the school elevators with her (elevators were only for the handicapped). She was enrolled in a research program and was promised the results of the efforts to find help and possible a cure for MD, but in all those 60 years of her life none was ever found. She died 19 years ago - and I see science is still "offering" this promise. So sad for those who have this condition, need the help, get set up to expect it, but nothing happens. My friend and her parents lived with that all those years ago and it is still happening.
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@Annabelle To answer your question, they don’t mention girls because Duchenne is a specific form of MD that exclusively affects males. There are many types of MD and the one treatment currently available on the market for Duchenne covers a specific genetic deletion, which is why many aren’t eligible. I have DMD and thankfully I am eligible for and receiving said treatment. I’ve had to deal with the guilt of getting treated when so many aren’t. We just need to have faith in science because it is advancing rapidly even if it doesn’t seem like it.
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@Annabelle
Duchenne is a type of MD that only affects boys.
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@Annabelle
She probably had a different form than Duchenne's. In order for a girl to have Duchenne's, she would have to have inherited X-chromosomes with the mutation from both her mother and her father. In that case, the father would have to have Duchenne's himself -- very unlikely since sufferers typically die in their 20's and are seriously disabled well before then.
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I find it interesting that Dr. Bigelow, the neurologist, finds the trials to be unjust because his son did not fulfill the criteria. I would want my neurologist to be a rigorous scientist!
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@Ameise The agony (I was going the write "pain", but that isn't even close) of seeing your child deteriorate, as you watch helplessly with your medical license on the wall, can make anyone abandon their training and respond with their heart.
I often treat the children of doctors, and they frequently respond this way. I get it. This man knows exactly what the future holds for his son, what it looks like at the end. Ignorance can be less painful, but he won't have that. He will know what each twitch and what each deep cough mean: things just got a little tougher.
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@Ameise My son is still walking which can be measured and quantified if different ways rather than how fast they can stand, such as measuring dystrophin on muscle biopsies and serum CK levels. I am grateful for trials and the scientific process and for boys like my son the stakes are high and the consequences devastating. We’re hoping our son might qualify when trials broaden their selection criteria.
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Our friend’s son died two years ago at the age of 17 after catching a bad cold. He was diagnosed w/ Duchennes at around age 4, and while his family and friends raised millions of dollars for Duchennes research and search for a cure, unfortunately it was too late to benefit Nash. This is tremendous news.
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Here is what happens with a poorly designed trial to DMD, but it could be in any disease.
Sarepta does a poorly designed clinical trial looking at the change in splicing rather than therapeutic outcome and with improper control groups. (It is easy to look up the details.)
In an incredibly odd set of events not reflective of how the FDA typically works, the FDA provides provisional approval of the drug (further testing required as there are no treatments available).
The drug enters the market with a $300,000 per year price tag. Insurance companies refuse to cover it as there are no studies demonstrating that the drug is effective.
Families need to decide if they think the drug is effective. If they do, they need to find $300K per year to pay for it. They will also be in a situation where their children are not eligible for clinical trials as they are on the other drug.
I do not know what I would do if I had to make the choice about putting my child on the drug.
Not every drug helps every patient, even when a drug has been demonstrated to be effective in most. If a clinical trial is designed poorly, it will never provide useful information. A drug with questionable efficacy is not really available to those who need it.
That being said, we need to be willing to pay for true innovation when it happens. These drugs, especially for rare diseases, do not come cheap.
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Designing clinical trials for Duchenne are particularly challenging. Some end points such as the six minute walk test may not provide a sensitive enough measure over the trial period.
I worked on a Duchenne drug that failed its primary endpoints in the major trials. Parents were reluctant to accept the failure in some cases because they thought they had observed slowed progression. Was this a placebo effect? Was this efficacy that did not rise to the trial end points? The scientist in me wants to follow the data. With so few patients the trials are small. I'm just glad the there are so many candidates in the pipeline now. I hope one works for these young men.
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My brother was diagnosed at the age of 3. And he passed away when he was 29. I found out i was a carrier at 7. I had my first son after his father passed away. He was 2 months old when diagnosed DMD. I was recently retested and found to be a manifesting carrier to Becker's MD. My son will be retested in June to see if he was misdiagnosed. My son is about to turn 13, transitioning to wheelchair and has had cardiomyopathy since the age of 6. So glad for CureDuchenne and all they do. Prayers for all families.
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Couldn't a lot of muscular dystrophy be identified before birth by genetic testing, which would give the parents an opportunity to make a decision about abortion?
Some muscular dystrophy is inherited, and some is not. So parents could be screened for inherited muscular dystrophy with prenatal genetic testing, so that they could test the embryo at an early stage. Some inherited diseases have been almost completely eliminated this way.
I realize that dystrophin is a large gene, that more than 50 mutations cause muscular dystrophy, and we don't know them all, so this wouldn't work all the time.
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@Norman Certainly prenatal genetic testing can be useful, but that does nothing for the people who currently have DMD. Additionally, not all parents would want or be able to access the prenatal testing and not all parents would decide to terminate even if a prenatal diagnosis was made.
I presume IVF may also be used by some families who have a family history of DMD?
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@Music Man
Pre-implantation genetic diagnosis of IVF embryos is currently possible. One cell is plucked from an 8 cell embryo, tested for MD, and if it is OK, the embryo is implanted.
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@Norman Jacob and Hudson are my two cousins and I know that my cousin Ryan and his wife Brooke are strong individuals who would have never chosen anything but to have their two incredible children. The impact they’ve had on all our lives in their few years on this planet make that decision seem absurd. Of course we do not wish them any suffering, but we all live full of hope for a better future, with all the research and testing that is yet to come.
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‘If the endpoint is improvement on a test for walking...’ The child with too much muscle loss for this test can be tracked after the test; did she continue muscle loss at the average rate seen overall, or was there less, different loss? Follow for 2, 3, years and see. The child with no muscle loss as yet- after the test, treatment, see if there is, again, average loss, or none.
As for insurance...an issue that could be resolved with legislation. The endpoint isn’t, shouldn’t be, walking. It should be “give them all a chance”- look at all results. It is often where discoveries are revealed. But good input- it can’t be easy, designing these life/death studies. If it were your child- what would you want?
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You can see here why successful new drugs are so expensive. While this article focused on the fate of the children, another article could have explained how expensive these types of trials are (along with prior research costs), how most of the trials fail, and how much companies need to charge to recover their own investment. When a potential therapy is not approved by the FDA, all the investment is lost. But Bernie Sanders, Donald Trump and a lot of politicians are united in painting as evil the doctors, scientists, investors, and company workers who try to perform these miracles.
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@William Meyers
Annual budget of the National Institutes of Health:
$40 billion
Cost of Iraq war:
$3 trillion
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@William Meyers
In many cases most of the research is funded by public NIH funds first.
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You are mixing up. basic research with drug development. Basic like characterization of mutations, their role in disease which is performed (usually) at academic centers. When it comes to drug development there are no grants! This type of work is in the vast majority of cases carried out by biotech companies and sometimes big Pharma. There is no grant money!
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The tone of this article demonstrates an obvious lack of understanding regarding scientific protocol development. The trials have stringent inclusion/exclusion criteria to reduce the number of potential confounders I.e. make the resulting data less noisy and more easily interpretable. It is hard to turn away sick people who aren’t quite sick enough or are too sick, but enrolling them and attempting to draw any conclusions from the data will not yield much of value toward future treatment strategies.
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I disagree. The tone seems meant to highlight the difference in creating a protocol for...say, a psoriasis treatment ....as opposed to a possibly life-saving/altering treatment for children. It is not beyond a computer’s AI ability to profile every child beforehand. Let the parents, or the child, decide on participation.
@Jo Williams the article notes that in MD, once muscle is lost, it cannot be regained. If the endpoint is improvement on a test for walking, for example, a child who is too far advanced in the disease will not improve. A child who has not lost function yet due to the disease will not improve. The drug will fail and it will get to no one.
Your suggestion that such things could be solved by AI is incorrect. For many of the diseases for which there is no cure, there have been few detailed studies on the natural history of the disease. I know this. I work at a company that develops drugs for rare diseases and the FDA provides grants to study the natural history of disease so people can set up clinical trials with meaningful outcomes.
When the FDA approved Sarepta's drug for DMD on questionable data, insurance companies refused to pay for the drug. A rigorous clinical trial must be done. At the end of the trial, if the drug appears to provide benefit, subjects in the placebo group will have access to the drug far before it comes to market.
Drug development is hard and expensive and does not work most of the time. A poorly planned study means no one ever gets the drug, even when it might be useful. That would be the worst possible outcome.
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@A, the tone of the article does no such thing. It presents the options very succinctly. The tone is one of parental desperation, hope and attempts to do the right thing for their children. We get that there are reasons for medicinal clinical trials; you don't have to lecture the author or the parents about the necessity for scientific rigor.
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Take them all. Profile, document each child, then take all of them. Sort out the results at the other end. For the ones already exposed to this virus, find another. Structured trials, verifiable results, for what? The next generation? Their parents will likely say the same; take them all.
In the randomness, in the jumble of results of various ages, stages, exposure, maybe that scientific miracle, ‘chance’, ‘error’, ‘unintended’, will reveal a cure- or at least a treatment.
A child’s life v. a verifiable study. Not a tough choice at all.
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@Jo Williams
You don't understand basic genetics.
If a treatment is designed to correct the defect of a specific gene, and the child doesn't have a defect in that gene, then there's no point to that treatment for that child. You might as well enroll him in a trial for Alzheimer's disease.
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Without further detail it is hard to say, but it almost appears in some of the trials mentioned that drug companies are structuring the trials for maximum success. Obviously, everyone wants these treatments to be effective, but my impression is that such narrow limitations serve as barriers that limit participation to only the "most likely to be cured". The difference between a child who can stand in 10 seconds to a child who can stand in 20 seconds cannot be so much, can it?
My heart hurts for all of these families.
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@SusseeQ I think it is more that the studies are structured to reduce the number of variables and make comparing patient outcomes easier. So, they want to take children who are all at the same stage of the disease. It's understandable that they want to do this (clinical trials are already difficult to analyze) but still heartbreaking for the families, particularly for older boys who are able to understand what's going on.
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@J
I recommend the movie, "The Inventor: Out for Blood in Silicon Valley" to illustrate what the researchers are trying to avoid.
It's about a diagnostic, not a therapy, but it shows you what happens when you try to develop medical products without going through the slow, careful, old-fashioned procedures.
Quote: "We didn't want people who were stuck in the old ways and document things."
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