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Genetic Linkage

Is CRISPR Gene Editing Doomed, Even As Gene Therapy Enters the Clinic?

Anyone watching the recent 60 Minutes segment on CRISPR would conclude that the gene editing technology is on the brink of pouring forth a cascade of cures. But a recent study reveals a mess of missing and moved chromosome parts in the wake of deploying the famed “molecular scissors.”

Invented in 2012, CRISPR brilliantly borrows a bacterial defense against infection. The “clustered regularly interspaced short palindromic repeats” are simple DNA sequences that serve as landing strips in a genome where engineered “guide RNAs” deliver an enzyme to a desired gene, amending or obliterating it. When the enzyme snips across the double helix, natural DNA repair ensues. Cas9 is an oft-used enzyme.

Precision

Unlike conventional gene therapy that adds a gene, sometimes hovering in a DNA loop outside a chromosome, CRISPR swaps in or removes a gene at a precise spot. But it took 27 years for the FDA to approve the first gene therapy, Luxturna, to treat a specific form of hereditary blindness, last December. So CRISPRed drugs won’t be hitting CVS or Walgreen’s shelves anytime soon.

The new report, in Nature Biotechnology, from researchers at the Wellcome Sanger Institute, isn’t the first to find a CRISPR glitch, and it certainly won’t be the last.

To continue reading go to DNA Science Blog, where this post first appeared.  Read More 
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Gene Therapy for Myotubular Myopathy: Early Signs of Success!

Paul Frase with his son Joshua.
Parents cherish developmental milestones, from a newborn’s grip of an offered finger; to an infant’s holding her head up the first time; to rolling over, creeping, and crawling; then to standing, cruising, and finally walking. Even kicking during a diaper change or yowling requires muscle strength and coordination. But a boy with X-linked myotubular myopathy (MTM) is so weak that even breathing is a huge struggle. If a baby survives the initial hospital stay, care at home becomes a full-time job and is only supportive, delaying the inevitable. That grim picture may be changing. Read More 
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Celebrating The Moms of Gene Therapy

Talia Duff has a rare form of Charcot-Marie Tooth disease (as well as trisomy 21 Down syndrome), with her mom Jocelyn.
As Mother’s Day and the annual meeting of the American Society of Gene and Cell Therapy approach, I’d like to update the stories of some of the moms I’ve written about, and introduce a new friend with perhaps the most astonishing gene therapy experience of all.

These women are some of the pioneers whose efforts will bring gene therapy to many more families. I wrote about Lori and Ilyce in my book The Forever Fix: Gene Therapy and the Boy Who Saved It, and met the others when they contacted me after reading it. Read More 
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French Anderson, “Father” of Gene Therapy, Released From Prison

Tonight French Anderson, 81, was released from state prison in California, after serving nearly a dozen years for “inappropriate touching and medical exams” of a girl, from 1997 to 2001, starting when she was ten.

Dr. Anderson headed the first clinical trial for gene therapy at the NIH in 1990, and he helped me when I was writing my book about the field, The Forever Fix: Gene Therapy and the Boy Who Saved It, which St. Martin’s Press published in 2012. I’d snail mail chapters to French’s wife Kathy, she’d take them to him, he’d mark them up with a pencil, and she’d mail them back.

French has always maintained his innocence and went to great effort to forensically discount the evidence against him, with several investigators demonstrating that the audiotape used to convict him– he appears to apologize to the victim – was spliced. He claims other evidence was falsified.

It is a complicated story involving the Chinese government’s interest in his discovery that an interleukin given to mice after exposure to high doses of radiation rescued them – a finding with profound military applications that was not the impetus for the study. French had been interested in treating radiation poisoning in cancer patients. A researcher in his lab patented the work in China – and she is the mother of the sexual abuse victim. I’ll leave it to others to assemble the puzzle pieces.

But I am sitting here absolutely stunned that one of the first things that French did when he returned home was to call me! Minutes ago! Read More 
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A Hiccup in Gene Therapy Progress?

Zebrafish, roundworms, fruit flies, mice, rats, rabbits, dogs, cats, pigs, and monkeys provide steppingstones to clinical trials to evaluate new treatments for people. The value of animal studies continues, even after a new drug shows promise or is approved.

A recent study on a gene therapy given to monkeys and pigs, similar to one that has already had spectacular results in children, may warn of possible dangers of escalating doses – or not.  Read More 
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From Blue Lights to Gene Therapy: The Intriguing History of Crigler-Najjar Syndrome

Seeing Crigler-Najjar syndrome among recent news releases announcing upcoming gene therapy efforts conjured immediate images of an Amish farmhouse with a spooky blue glow emanating from an upstairs bedroom, where a small child, clad only in diapers and wearing goggles, slept beneath a “light canopy” suspended from the ceiling. The light – phototherapy or “bili lights” – breaks down the accumulating bilirubin that the tiny yellow body beneath cannot.

Most cases of neonatal jaundice are due to a transient blood type incompatability or blocked bile ducts, and vanish within days. Not so

Crigler-Najjar syndrome, which hampers the ability to convert the bile pigment bilirubin into a soluble form that easily exits in feces. Read More 
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Incurable Arthritic Knees? Gene Therapy Offers New Hope

Imagine a single injection into the knee vanquishing painful arthritis – forever. Gene therapies aimed at two molecular targets will likely make that possible, with one, Invossa, already approved in South Korea.

“Arthritis” is a catch-all term for more than 100 varieties of joint inflammation. In the US, more than 30 million people have osteoarthritis (OA). The knee is particularly vulnerable, with arthritis there plaguing 10% of men and 13% of women aged 60 years or older.

Four events contribute to arthritis: inflammation, an increase in the volume of synovial fluid that fills joints, breakdown of the joint, and underlying bone damage.  Read More 
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Two New Ways to Treat A Deadly Disease: Spinal Muscular Atrophy

I don’t think I’ll ever tire of covering new ways to treat genetic diseases that I’d always thought hopeless. Teamed with expanded newborn screening, the brave new treatments may even be able to prevent symptoms.

Recently reports in the medical journals of success seem to be accelerating, despite the long regulatory  Read More 
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As Blindness Gene Therapy Nears the FDA Finish Line, A Shout-Out to Activist Families

(NHGRI)
On a spectacular September Sunday in 2008, 8-year-old Corey Haas, using his cane and holding his mother’s hand, stepped tentatively forward on the pathway leading into the Philadelphia zoo. Hearing kids yelling about the giant balloon hanging above the zoo, he looked up – and screamed. It was the first time he’d seen the sun. Corey was headed toward certain blindness when he’d had gene therapy at Children’s Hospital of Philadelphia, just days earlier.

So begins the talk I’ve given many times since publication of my book, "The Forever Fix: Gene Therapy and the Boy Who Saved It.

Last Thursday, I was glued to my laptop, watching and listening to physicians, researchers, family, and patients present their cases for FDA approval of
Luxturna (voretigene neparvovec), the gene therapy that Corey, now a high school senior, received. He and dozens of others participating in several clinical trials can now see, thanks to the gene therapy for RPE65-mediated inherited retinal dystrophy. The treatment introduces functioning genes into the thin layer of pigmented cells that hugs the rods and cones – one time. Read More 
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Upchuck Factor: Alcoholism Targeted With Novel Gene Therapy

The intense nausea that follows drinking alcohol for people with a certain gene variant may become the basis for a gene therapy to prevent alcohol use disorder, the new medicalized term for alcoholism. It would work much like the drug Antabuse, used for more than half a century, but on a less fleeting permanent basis.

Cells process ethanol, the type of alcohol in beverages, in two steps, each controlled by an enzyme. First ADH (alcohol dehydrogenase) speeds the reaction of ethanol to form acetaldehyde. Then ALDH2 (aldehyde dehydrogenase 2) breaks down the acetaldehyde into acetic acid, aka vinegar.

But if that second enzyme isn’t working well, acetaldehyde builds up, and nausea ensues. Because throwing up is so unpleasant, individuals who tend to upchuck after drinking avoid alcohol. Read More 
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