Curing disease by repairing faulty genes

[Confounding]

Here is a link to the research paper: http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3471.html

Curing disease by repairing faulty genes

The genome-editing technique known as CRISPR allows scientists to clip a specific DNA sequence and replace it with a new one, offering the potential to cure diseases caused by defective genes. For this potential to be realized, however, scientists must find a way to safely deliver the CRISPR machinery and a corrected copy of the DNA into the diseased cells. MIT researchers have now developed a way to deliver the CRISPR genome repair components more efficiently than previously possible, and they also believe it may be safer for human use. In a study of mice, they found that they could correct the mutated gene that causes a rare liver disorder, in 6 percent of liver cells — enough to cure the mice of the disease, known as tyrosinemia. “This finding really excites us because it makes us think that this is a gene repair system that could be used to treat a range of diseases — not just tyrosinemia but others as well,” says Daniel Anderson, associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

 

[waltky]

Gene therapy drug approval for GSK...

Gene therapy drug approval granted to GSK
Fri, 27 May 2016 - Regulators have given one of the world's largest drug companies approval to sell a new gene therapy.

The treatment is for an illness called ADA-SCID which prevents babies from fighting off everyday infections. This is the first approval for a genetic therapy granted to a large multinational drug company, GSK. Commentators say the development marks the beginning of many more genetic medicines from so-called "Big Pharma". The condition is extremely rare and affects around two dozen babies each year. Approval of the gene therapy paves the way for the development of treatments for more widespread illnesses such as thalassemia and sickle cell disease. Hundreds of inherited disorders such as cystic fibrosis, muscular dystrophy and many types of blindness are caused by faulty genes.

Hype

The aim of gene therapies is to cure the disease by introducing healthy copies of the gene into the patient. And the big advantage of the treatment is that it only needs to be given once and it offers a potentially permanent cure. The idea first emerged with much hype 30 years ago. At the time, large drug companies such as Novartis and Roche were at the forefront of the technology. Advocates of gene therapy said it would cure everything but, for 20 years, it cured nothing. The practicalities of introducing the right gene in the right cells and getting them to stick proved more difficult than first thought. There were huge setbacks for the technology in the early days.

Difficulties

In 1999, an 18-year-old man Jesse Gelsinger died in a clinical trial of a gene therapy to treat a liver disease. The virus used to transfer the gene into his cells triggered his immune system into overdrive which led to multiple organ failure and brain death. Three years later, children being treated in Paris for a problem with their immune system developed leukaemia because the healthy gene was inserted too close to a cancer-causing gene which consequently became active. The setbacks saw large drug companies withdraw from research in the field. Small biotechnology companies and publicly funded research groups persevered and, in time, many of the early difficulties were overcome.

As well as today's approval of GSK's treatment, which the company calls Strimvelis, in 2012 regulators gave the green light to a gene therapy called Glybera for a pancreatic disorder and another last year called T-Vec for skin cancer. According to Prof Alan Boyd, who is president of the Faculty of Pharmaceutical Medicine and a pioneer in the development of gene therapy, more approvals are likely to be given in the next few years. "Most of the hard work has been done by small companies. But as some of these products have come closer to market, Big Pharma has come back in," he says.

Significant step

 

[ScienceRocks]

We may end up curing heart disease or avoiding it all together, cancer and many other ailments that effect humanity. Can't say that praying every sunday comes anywhere close.

 

[waltky]

Finding the roots of disease...

DNA catalogue helping find roots of disease
Fri, Aug 19, 2016 - ADVANTAGES: A genetics expert not involved in the new work said there is little doubt it will help accelerate and refine the search for the causes of many diseases

A huge catalogue of human DNA is helping researchers find tiny glitches that cause disease, in part by pointing out some false leads. The database, with genetic codes from more than 60,000 people, is aimed at researching rare diseases that are generally caused by a single malfunctioning gene. Most of these diseases are so uncommon that the general public has never heard of them, but there are thousands of such conditions, and as a group they affect about 1 percent of births. Better accuracy in identifying the genetic cause of a person’s disease provides a “clear and direct benefit to patients,” said Daniel MacArthur of the Broad Institute in Cambridge, Massachusetts, and Massachusetts General Hospital in Boston.

He is senior author of an analysis published on Wednesday in the journal Nature by researchers who compiled the database, which draws on DNA data from more than two dozen disease studies. It went online in 2014 and has since been consulted more than 5 million times, he said. For rare diseases, doctors try to find the genetic cause by analyzing the patient’s DNA. However, everybody carries tens of thousands of minute differences from the standard DNA code, and the goal is to find which one or two of them is making the person sick. Researchers frequently do that through guilt by association. If a variation shows up in a patient, but it is never seen or extremely rare in others, it might be fingered as the cause of disease.

The challenge is getting enough DNA from the general public. If the sampling is too small or not comprehensive enough for diverse populations, a variant might be wrongly blamed as the cause of the patient’s problems. A better sampling might show the variant actually appears in healthy people often enough that it is clearly not making anybody sick. False leads can harm patient care, including in some cases missing out on treatments, MacArthur said. An example of such a “genetic misdiagnosis” was presented on Wednesday in an unrelated study in the New England Journal of Medicine. It focused on an inherited disease called hypertrophic cardiomyopathy, which thickens the heart muscle and can interfere with pumping blood.

Examining three years of records from a testing lab, it found that seven patients were told they carried one of two DNA variants that had been linked to the heart disease. Both variants were later reclassified as benign. At least five of the patients were of African ancestry. If the original studies of those variants had included enough black Americans in their samples, they probably would not have reached the wrong conclusion, the Harvard researchers said. They said the new DNA catalogue, dubbed ExAC, is well-equipped to avoid such errors. It provides a far more comprehensive collection of DNA variations than has been available in the past. The roughly 10 million tiny variations listed are from people of European, African, South Asian, East Asian and Latino ancestry.

MORE

 

[waltky]

Two Toronto scientists honoured for their work on thalassemia breakthrough...

Two Toronto scientists honoured for their work with breakthrough drug
June 8, 2017 | Two Toronto scientists, Michael Spino and Fernando Tricta, will jointly receive the Humanitarian of the Year Award from Cooley’s Anemia Foundation Gala in New York City on June 8 for their work on a medication that clears excess iron from the bodies of patients with thalassemia, a red blood cell disorder.

Thalassemia is a genetic disease in which the body doesn’t produce enough red blood cells, so patients require blood transfusions every two to four weeks for their entire lives. A side effect of those transfusions is a buildup of iron around vital organs — most commonly, the heart. Before the approval of deferiprone, patients with thalassemia had to undergo eight- to twelve-hour long overnight injections directly into their stomach. “I tried it once,” said Tricta. “I tried to sleep with this. I injected myself for one night and it’s not a pleasant experience. And this is every single day.” With deferiprone oral tablets, patients simply take a few pills a day.

They never gave up on us

Maria Hadjidemetriou was diagnosed with thalassemia when she was two years old. “We woke up with abscesses, black and blue marks and bumps that looks like tumors. It’s very uncomfortable,” she said. Tricta is from Brazil, and started his career by founding the first Brazilian treatment centre for children with thalassemia. He saw the daily struggle and pain of the injections wearing on the kids and their parents, and began searching for an easier solution. “We knew that if they would not take those injections at least five days a week, every week, the (chance) for them to survive would be very little. But you can understand how hard it is,” he said. “The problem is when they become adolescents and then they think that, ‘nothing’s gonna happen to me,’ and they decrease their use of medication. That’s when we used to see the patients die. They go into heart failure and they die, in front of our eyes.”

Fernando Tricta and Michael Spino.​

Tricta took notice of a group of scientists from London’s King’s College, who created a drug called deferiprone. In 1996, ApoPharma’s Michael Spino asked if Tricta would assist them in developing the drug. Initially, he said no, as he was cautious about making the leap from academia to a pharmaceutical company, but Spino was eventually able to convince him it was in the public interest. “He said the commercial interests would never trump the welfare of the patients,” said Tricta. Although licensed for use in Europe and Asia for years, deferiprone was approved in the U.S. in 2011, and in Canada in 2015 — but not without controversy.

In 1989, Toronto haematologist Nancy Olivieri began to study the drug. Later, with her research partially funded by Apotex, the mother corporation to ApoPharma, Olivieri became concerned about the efficacy and safety of the drug. Apotex tried to block her from telling patients about her concerns, noting that she had signed a confidentiality agreement. She told patients anyway, and Apotex ended the portion of the study that she was working on. Apotex contested her findings based on results from their clinical trials. In 1998, Olivieri and seven others wrote a paper published in the New England Journal of Medicine that suggested deferiprone led to progressive hepatic fibrosis. Regardless, the drug is now used in more than 50 countries.

Hadjidemetriou describes deferiprone as “fantastic.” “My breathing got better … And it got better and better and better as the days went on.” She holds Tricta and Spino in high regard. “They never gave up on us.” “As a clinician, I could not have greater satisfaction in my life that I have participated in something that has impacted so many lives,” said Tricta. “I’m very honoured and humbled by this award.”

Two Toronto scientists honoured for their work with breakthrough drug

 

[anotherlife]

We may end up curing heart disease or avoiding it all together, cancer and many other ailments that effect humanity. Can't say that praying every sunday comes anywhere close.

Soon that praying will be for the permission to die. That won't come close either.