Gene editing of blood stem cells can correct disease-causing mutations

Recent advances in gene editing technology, which allows for targeted repair of disease-causing mutations, can be applied to hematopoietic stem cells with the potential to cure a variety of hereditary and congenital diseases. Gene editing can overcome many of the obstacles associated with gene addition therapies, but this young field still faces many challenges before it is ready for human testing, as discussed in a Review article published in Human Gene Therapy.

The article entitled "Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles" is part of a special joint issue on stem cell gene therapy in Human Gene Therapy and Stem Cells & Development guest edited by Luigi Naldini, MD, Scientific Director, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy. A special "upside-down" print issue will be distributed at ESGCT/ISSCR Florence 2016 in October.
Gene Editing, Epigenetic, Cloning and Therapy 

Kyung-Rok Yu, Hannah Natanson, and Cynthia Dunbar, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, describe how earlier gene addition strategies and the hurdles they encountered have informed the current development of gene editing approaches. The authors present the state-of-the-art in gene editing technology and the potential to apply these novel techniques to repair genetic flaws in hematopoietic stem cells, which give rise to the different types of cells in blood, and then to test those strategies in human clinical trials.
"Gene editing is the hottest new technology in gene therapy. The use of this approach to genetically modify hematopoietic stem and progenitor cells is very promising, but requires a careful assessment," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "This mini-review by Dr. Dunbar's group at NIH provides a very insightful analysis of recent advances and current limitations of this approach

Smartphone App may offer needle free way to screen Blood for Anemia

Carolina Henriques:

Engineers and computer scientists from the University of Washington (UW) have developed what they are calling a HemaApp, designed to detect hemoglobin concentration using simply a smartphone camera and a little extra lighting — rather than needles or an expensive, specialized machine.

Measuring hemoglobin, a protein found in red blood cells, is particularly important for people with anemia and other blood disorders, who require frequent blood draws. The app is also thought to detect abnormal hemoglobin properties, which could help screen for diseases such as sickle cell anemia.

Described in an article that won a  ‘Best Paper’ award, HemaApp will be presented at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016), taking place on Sept. 15 in Germany.

Healthcare providers now measure hemoglobin levels by drawing blood with a needle or an intravenous line, or by using Masimo Pronto, an U.S. Food and Drug Administration (FDA)-approved device that measures hemoglobin noninvasively by clipping a sensor onto a person’s finger. The device, however, is too expensive for many medical facilities worldwide.

“In developing countries, community health workers have so much specialized equipment to monitor different conditions that they literally have whole bags full of devices,” Edward Wang, the study’s lead author and UW electrical engineering doctoral student, said in a press release. “We are trying to make these screening tools work on one ubiquitous platform — a smartphone.”

HemaApp works by analyzing the color of  blood when light is shone from the phone’s camera — with a little help, for now, from external lighting — through a patient’s fingers, and then estimating hemoglobin concentrations. By analyzing how colors are absorbed and reflected across wavelengths, it can detect concentrations of hemoglobin and other components, like plasma.

HemaApp was tested in an initial trial including 31 patients. Requiring only one smartphone modification, HemaApp performed as well as the Masimo Pronto, the researchers said.

To make sure that the technology works on different skin tones and body masses, the team developed processing algorithms that use the patient’s pulse to differentiate between the properties of the patient’s blood and the physical aspects of the patient’s finger.

The UW team tested the app under three different scenarios: using the smartphone camera’s flash alone, in combination with a common incandescent lightbulb, and with a low-cost LED lighting attachment – additional light sources fall onto other sections of the electromagnetic spectrum that aren’t now found on all smartphone cameras.

“New phones are beginning to have more advanced infrared and multi-color LED capabilities,” said Shwetak Patel, the paper’s senior author and an endowed professor in Computer Science and Engineering and Electrical Engineering at UW. “But what we found is that even if your phone doesn’t have all that, you can put your finger near an external light source like a common lightbulb and boost the accuracy rates.”

In the initial studies, HemaApp’s hemoglobin measurements had a 69% correlation to a patient’s complete blood count (CBC) test, a 74% correlation when using a common incandescent light bulb, and an 82% correlation using a small circle of LED lights attached to the phone. Masimo Pronto scored an 81% correlation to the blood test.

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The app is not meant to replace blood tests, but results suggest that it could be an effective and affordable screening tool to determine if blood testing is needed.  When used in anemia screening, HemaApp accurately identified 79% of the cases of low hemoglobin levels and 86% when aided with light sources.

“Anemia is one of the most common problems affecting adults and children worldwide,” said Doug Hawkins, a UW Medicine, Seattle Children’s Hospital, and Seattle Cancer Care Alliance pediatric cancer specialist. “The ability to screen quickly with a smartphone-based test could be a huge improvement to delivering care in limited-resource environments.”

MegaFood - Blood Builder, Promotes Healthy Blood Cell Production & Circulation, 90 Tablets (Premium Packaging) Further research steps include further testing of HemaApp to collect additional data and improve accuracy rates. The research project received financial assistance from the Washington Research Foundation.

Stem cell transplant cures children with sickle cell anemia, says Alberta hospital

7 girls, 2 boys cured in what lead doctor considers unprecedented treatment

By Lisa Monforton,

Cardelia Fox has a tattoo on the inside of her right forearm with the words "Set free." 

It's a reminder of how a cutting-edge transplant at the Alberta Children's Hospital cured her of sickle cell anemia and a life of hospital stays and blood transfusions.

The chronic genetic blood disorder caused Fox to have three childhood strokes — the first when she was only six months old. She would have two more at age six and 10.

Until the age of 17, she had been in and out of hospital and previously needed to have monthly life-saving blood transfusions.

The year Fox turned 17 she was one of the first patients to undergo the stem cell transplant procedure at the Alberta Children's Hospital.

The success of the procedure has captured interest from around the world, says Dr. Greg Guilcher, a pediatric oncologist who leads the sickle cell blood and marrow transplant program in Calgary.

Dr. Greg Guilcher is the lead doctor for the stem cell transplant procedure at Alberta Children's Hospital.

"To our knowledge, no one else is offering this protocol in children with sickle cell anemia," said Guilcher, who is also an assistant professor in the departments of oncology and pediatrics at the University of Calgary's Cumming School of Medicine.

What sets the Calgary procedure apart from other sickle cell anemia cures in young children is the lead up to the transplant. 

"​This protocol uses the 'lightest' doses of medication — no chemotherapy but immune suppressing drugs only, with a low dose of radiation," said Dr. Guilcher in a statement. 

While the protocol was developed and is used in the U.S., Dr. Guilcher said he's not aware of any other hospital using it on children.

More exciting is the fact that there have been no incidents of stem cell rejection. 

"We're getting phone calls and emails from around the world from interested parents and other doctors. We think we're ahead of the curve in offering this curative therapy as a standard of care."

Sickle cell anemia is a chronic illness where blood vessels can become blocked when blood cells change into a sickle shape, potentially affecting every organ and causing strokes, lung disease heart strain and spleen and bone damage. With advanced drug therapy treatment, life expectancy is 55- to 60-years-old.

The success of the procedure, which was first performed in Calgary in 2009, has cured seven girls and two boys to date.

Life-changing, says patient

"Before the stem cell transplant I felt like I was trapped," says Fox, whose sister Tamika Allen was a perfect match — a rare one in five occurrence within families. "Without this treatment I would likely still be at Foothills getting blood transfusions every month."

Tamika Allen, left, was a perfect stem cell match to her sister Cardelia Fox, which allowed her to have a procedure curing her of sickle cell anemia. (CBC)

Once Allen found out she was a full match, she didn't think twice about helping her sister.

Without a family match, the transplant procedure is generally considered too risky to perform.

"When we learned I was a match there was never any question of whether or not I'd do it," said Tamika, now 22. "Of course I'm going to do this for my sister. It was such a good feeling to be able to help make her life better — now I call her my mini-me."

Rising incidence in Canada

People of African descent are most often affected by sickle cell anemia. One parent can pass on the mutation and not cause the illness, but the illness results when both parents pass it on.

Fox's grandmother died at the age of 35 because of complications from the disease.

In 2008, the Sickle Cell Clinic at the children's hospital regularly treated 16 children.

Now there are more than 80, primarily because of immigration, says Dr. Mike Leaker. He is the head of the clinic, which sees patients from Alberta, Saskatchewan and eastern B.C.

"We now have some excellent medications that can change the course of the illness for many patients," said Leaker. "But a drug is still a treatment, not a cure. For families the word 'cure' is incredibly powerful."

Guilcher is expecting continued interest in the procedure from around the world

Sickle Cell Anemia: From Basic Science to Clinical Practice