Gene therapy’s time seems to have come

Once considered too risky, now offering hope to patients long without it

By Carolyn Y. Johnson | Source: The Boston Globe

Two boys born with a fatally flawed gene that leaves them defenseless against common infections have returned to their homes in Argentina and Chile after receiving an experimental gene therapy at Boston Children’s Hospital.

Untreated, babies with their “bubble boy” disease would die in infancy, but in 2010 and 2012, doctors inserted good copies of the gene into their bone marrow cells, restoring the boys’ immune systems. Both are now well into toddlerhood.


Kirsti Pigney is participating in a trial for gene therapy to treat blindness. She can’t tell whether the therapy is working, but said her vision hasn’t worsened.

Meanwhile, Kirsti Pigney, a 76-year-old from Taunton who woke up one day unable to see, is participating in a safety trial of a gene therapy being tested by Cambridge-based Genzyme for a form of blindness. She recently had a virus, modified to carry a therapeutic gene, injected into one of her eyes.

Years after it was hyped, then vilified after the death of a teenager, then mostly forgotten by the general public, gene therapy has rebounded, and hospitals, companies, and investors in the Boston area have jumpedon the bandwagon. Patients are enrolling in a growing number of clinical trials here, and in some cases showing dramatic improvement. The technique, in which doctors “infect” patients’ cells with viruses engineered to carry useful genes, has matured and evolved.

It is a future few could have predicted a decade ago. Once trumpeted as a possible panacea for diseases ranging from sickle cell anemia to cystic fibrosis, gene therapy faced serious questions after the high-profile death of an Arizona teenager in a clinical trial in 1999. The case seized national attention, led to inquiries into failures of regulatory oversight, and scared away many investors. But some researchers continued to work to overcome the safety and technical hurdles.

“When I first went to UMass, several prominent scientists said, ‘What do you mean, gene therapy? They tried that and it didn’t work,’ ” said Dr. Terence Flotte, the dean of UMass Medical School, who has been working in the field since the late 1980s.

Over the years, scientists have improved the safety of the viruses used to insert good copies of genes into cells. Cautiously, they began to test the technique in people again. In 2008, two groups of researchers reported restoring some vision in people with a rare retinal disease. The next year, eight out of 10 children with bubble boy disease were cured in a European trial.

Scientists reported in 2010 that a French man with a genetic blood disorder no longer needed monthly transfusions after being treated by a gene therapy made by Cambridge-based Bluebird Bio.

Pigney and her husband Keith thoroughly researched the procedure when her doctor mentioned the Genzyme trial. Instead of replacing a defective gene, the treatment inserts a gene directing eye cells to produce a protein that inhibits the abnormal growth of blood vessels — the reason for her vision loss.

Undaunted by gene therapy’s checkered history, the couple was intrigued by recent promising results. Pigney had always enjoyed sewing and crocheting, and now can do those things only if her husband threads the needle. She can’t write or drive a car or read small print.

“I tend to be a little bit optimistic, and I dreamed about my eyesight coming back. I never felt afraid of the injection,” Pigney said. “They’ve given me so many now. I’m like a pincushion.”

She can’t tell whether the therapy is working, but said her vision hasn’t gotten worse. At this point, the trial is testing only the safety and dosage.

With a handful of experimental trials open or in the works at local hospitals, gene therapy seems to have found its footing.

Dr. David Williams, director of translational research at Boston Children’s Hospital, said he plans this summer to bring together key players from area hospitals to share the expertise Children’s has gained from launching trials. The trials include one for a rare, genetic immune system disease called Wiskott-Aldrich syndrome and another scheduled to begin this summer for the neurodegenerative disease adrenoleukodystrophy, best known from the role it played in the movie “Lorenzo’s Oil.”

UMass Medical School has several active trials for patients with a genetic flaw that leads to lung and liver disease; the most advanced trial one has treated eight patients. They have also treated two patients, including Pigney, with age-related macular degeneration. At scientific meetings, Flotte, the UMass dean, said he’s begun to notice something he hadn’t seen before: lots of interest from the business community — including drug companies and investors — eyeing a hot field.

Bluebird Bio went public earlier this month, raising $101 million. The first gene therapy, Glybera, made by the Dutch company uniQure, was approved in Europe last year, for a rare disease that causes fat to build up in the bloodstream. A spokesman for the company said it had requested a meeting with the US Food and Drug Administration to get clarity on the approval process.

As the technology has matured, the understanding of its possible uses has also expanded as scientists have learned more about basic biological mechanisms. UMass Medical School biologist Craig Mello’s co-discovery of a way to turn off genes won him a share of a Nobel Prize in 2006 — and it introduced the possibility that gene therapy could be used not just to introduce good copies of genes, but to shut down malfunctioning ones.

Dr. Robert Brown, a professor of neurology at UMass who studies ALS, said that the ability to do more than just add good genes has ignited broader interest in the technique.

“Many of these diseases have a need for silencing” a gene, Brown said. “In Huntington’s, some forms of Parkinson’s, and most forms of familial ALS, the real challenge is not loss of [gene] function, but how to respond” to mutated genes that are producing proteins that harm the body.

Animal testing in primates or other large animals set to begin this year are beginning to change the discussion about the potential for using gene therapy in those neurodegenerative diseases.

“I’ve been doing this for many years starting in the early 1980s, and we’re now at a point where we’re talking about when we would treat the patient,” said Dr. Neil Aronin, a professor of medicine and cell biology at UMass who has long studied Huntington’s. “We didn’t even have that discussion before.”


Rare disease tweet chat: how can rare diseases gain more media attention?

Imageby Rebecca Aris


Rebecca Aris highlights the recent tweet chat on the topic of rare diseases hosted by pharmaphorum.

On Friday 1st February this year, pharmaphorum hosted a tweet chat on the topic of rare diseases. Many rare disease patients came together through this social media channel to discuss topics in this space. This article details some of the responses and themes that arose.

How has social media affected rare disease patients?

The first question we asked participants was how social media has affected rare disease patients. Here are some of the responses we had to this question:-

  • Information via social media is power for rare disease patients.
  • Social media has provided an amazing opportunity for rare disease patients to find each other and share support.
  • Social media allows patients the opportunity to engage with companies who are developing drugs for rare diseases.
  • In Wilson Disease group, someone newly diagnosed from the UK posted a question and got replies from people in five countries in approximately 36 hours.
  • Social media has given people with cystic fibrosis the tools to put real pressure on public healthcare systems to fund new drug.

So it seems that social media offers information, a platform to connect, support and access to global communication – instantly.

Rare disease patients and clinical trials

We asked our tweet chat participants how they found clinical trials and how they calculated the risk of participating. Here are their answers:-

Patients are clearly quite clued up when it comes to resources in this area. They naturally still express concern over the fact there is often no alternative treatment option, and they want to be as informed as possible.

How can we raise awareness of rare diseases?

Rare diseases need more media attention! This was a message that echoed throughout the chat. Rare diseases need more media press so the public can see that this is a common problem that needs to be addressed. Some popular responses to this question from the tweet chat are below:-

  • One tweet, one post at a time.
  • Sharing the simple fact that collectively rare diseases are not rare. One in ten Americans lives with a rare disease.
  • Need high profile media attention.
  • Increased interaction between all relevant stakeholders from patients to regulators.

So how can we gain media attention in this area? The question remains and given the fact that collectively rare diseases are common it’s clearly time that this area received more attention.

How can we reduce isolation of rare disease patients?

When interviewing rare disease patients a common topic that arises is the feeling of isolation that rare disease patients experience. When questioned on how we could reduce this feeling of isolation our tweet chat participants came up with the following suggestions:-

  • So many wonderful online options like @inspire @patientslikeme @wegohealth and groups like @RareConnect and @bensfriends can also help
  • Check out #pcori.
  • Social media, especially Facebook groups can reduce isolation of rare disease patients.

Online rare disease communities, it seems, really do make a difference in offering support and reducing isolation.

If you could tell pharma one thing – what would it be?

Many patients express an interest in wanting to be able to communicate more openly with pharma. We asked our tweet chat participants if they could tell pharma one thing what would it be. Some of the responses were as follows:-

  • Newly diagnosed rare disease patients want pharma to extend to support groups and offer an explanation of the drug development process.
  • Rare disease patients need safe, effective treatments and they want to work together with pharma.
  • We want a cure, but we’ll take a treatment.

A common theme was that they wanted to work more closely with pharma and wanted more education on how pharma works and, specifically, the drug development process.

As a rare disease patient, what gives you hope for the future?

We closed the tweet chat by asking what it is that gives rare disease patients hope for the future. Here is what they said…

  • Other inspiring rare disease patients / families.
  • More funds being allocated for research into rare disease treatments.
  • Incredible gene therapy advances.
  • More venues to communicate.
  • Industry interest, young generation of academic researchers.

It seems that rare disease patients are hopeful that therapeutic advances, increased communication with pharma and increased funds in this area are contributing toward the treatments and cures of the future.

We’d like to thank those who participated in the chat for sharing their thoughts with us and engaging in this lively debate.

You can view the whole conversation on Appeering here or on Storify here.