Sickle cell disease. Image: Flickr

Sickle cell disease is a slow, vicious killer. Most people diagnosed with the red blood cell disorder in the US live to be between 40 and 60. But those years are a lifetime of pain, as abnormal, crescent-shaped hemoglobin stops up blood flow and deprives tissues of oxygen, causing frequent bouts of agony, along with more severe consequences like organ damage. Now, after decades of searching for a cure, researchers are announcing that, in at least one patient, they seem to have found a very promising treatment.

Two years ago, a French teen with sickle cell disease underwent a gene therapy treatment intended to help his red blood cells from sickling. In a paper published Thursday in the New England Journal of Medicine, the researchers revealed that today, half of his red blood cells have normal-shaped hemoglobin. He has not needed a blood transfusion, which many sickle cell patients receive to reduce complications from the disease, since three months after his treatment. He is also off all medicines.

To reiterate, the paper is a case study of just one patient. Bluebird Bio, the Massachusetts biotech company that sponsored the clinical trial, has treated at least six other trials underway in the US and France, but those results have not yet been fully reported. The gene therapy has not worked quite as well in some of those other patients; researchers say they are adjusting the therapy accordingly. It is also possible that the boy may eventually experience some blood flow blockages again in the future.

The results, though early, are encouraging. They represent the promise of new genetics technologies to address a disease that has long been neglected and tinged with racism. Sickle cell disease affects about 100,000 people in the US, most of whom are black. It is an inherited genetic disease caused by a mutation of a single letter in a persons genetic code.

This single-letter mutation makes it a promising candidate for cutting edge technologies, like the gene-editing technique CRISPR-Cas9, and other gene therapies. Recently, a rush of new research has sought to address it. Two other gene therapy studies for sickle cell are underway in the US one at UCLA and another at Cincinnati Childrens Hospital. Yet another is about to start in a collaboration between Harvard and Boston Childrens Hospital. Last fall, researchers all demonstrated the ability to correct the mutation in human cells using CRISPR, though that strategy will yet have to surpass significant scientific and political hurdles before reaching clinical trials.

In the new study, researchers took bone marrow stem cells from the boy and fed them corrected versions of a gene that codes for beta-globin, a protein that helps produce normal hemoglobin. The hope was that those altered stem cells would interfere with the boys faulty proteins and allow his red blood cells to function normally. They continued the transfusions until the transplanted cells began to produce normal-shaped hemoglobin. In the following months, the numbers of those cells continued to increase until in December 2016, they accounted for more than half the red blood cells in his body. In other words, so far so good.

Currently, the only long-term treatment for sickle cell disease is a bone marrow transplant, a high-risk, difficult procedure which many patients are not even eligible for. Pain and other side-effects are treated with blood transfusions for temporary relief. New technologies offer the hope of a solution that could provide long-term relief and allow patients to live some semblance of a normal life.

For decades, gene therapies have been touted as a cure for everything. But so far, successes have been infrequent, and often for very rare diseases. But early success in treating sickle cell disease means that soon, if were lucky, the benefits of this technology may reach hundreds of thousands of people.

[New England Journal of Medicine]

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Will Sickle Cell Be the Next Disease Genetic Engineering Cures? - Gizmodo

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Challenges in identifying the best source of stem cells ...

A team led by scientists from The Scripps Research Institute (TSRI) has found a simple method to convert human skin cells into the specialized neurons that detect pain, itch, touch and other bodily sensations. These neurons are also affected by spinal cord injury and involved in Friedreich's ataxia, a devastating and currently incurable neurodegenerative disease that largely strikes children.

The discovery allows this broad class of human neurons and their sensory mechanisms to be studied relatively easily in the laboratory. The "induced sensory neurons" generated by this method should also be useful in the testing of potential new therapies for pain, itch and related conditions.

"Following on the work of TSRI Professor Ardem Patapoutian, who has identified many of the genes that endow these neurons with selective responses to temperature, pain and pressure, we have found a way to produce induced sensory neurons from humans where these genes can be expressed in their 'normal' cellular environment," said Associate Professor Kristin K. Baldwin, an investigator in TSRI's Dorris Neuroscience Center. "This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury."

The report by Baldwin's team appears as an advance online publication in Nature Neuroscience on November 24, 2014.

In Search of a Better Model

The neurons that can be made with the new technique normally reside in clusters called dorsal root ganglia (DRG) along the outer spine. DRG sensory neurons extend their nerve fibers into the skin, muscle and joints all over the body, where they variously detect gentle touch, painful touch, heat, cold, wounds and inflammation, itch-inducing substances, chemical irritants, vibrations, the fullness of the bladder and colon, and even information about how the body and its limbs are positioned. Recently these neurons have also been linked to aging and to autoimmune disease.

Because of the difficulties involved in harvesting and culturing adult human neurons, most research on DRG neurons has been done in mice. But mice are of limited use in understanding the human version of this broad "somatosensory" system.

"Mouse models don't represent the full diversity of the human response," said Joel W. Blanchard, a PhD candidate in the Baldwin laboratory who was co-lead author of the study with Research Associate Kevin T. Eade.

A New Identity

For the new study, the team used a cell-reprogramming technique (similar to those used to reprogram skin cells into stem cells) to generate human DRG-type sensory neurons from ordinary skin cells called fibroblasts.

Read this article:
Pain and itch in a dish: Scientists convert human skin cells into sensory neurons

SAN FRANCISCO – A move to tighten
budget controls on grants from the $3 billion California stem cell
agency stalled Monday, but it appears that the plan is headed for
ultimate approval.

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