Genetic therapy offers hope to people facing fatal diseases

http://www.abc.net.au/7.30/content/2015/s4166968.htm

Transcript
LEIGH SALES, PRESENTER: Imagine having to go to hospital for a blood transfusion every month of your life. That's the case for the person you're about to meet.

Stacey Wong has thalassemia, an inherited blood disease that can be fatal.

Now, Australian doctors are using genetic therapy in the hope of offering patients like Stacey a cure.

The ABC's medical reporter, Sophie Scott, has this exclusive report.

SOPHIE SCOTT, REPORTER: Stacey Wong has spent much of her life in hospitals.

Now 26, Stacey's had to have blood transfusions every month of her life just to stay alive, but today could be her last session on the machine.

JOY HO, ROYAL PRINCE ALFRED HOSPITAL: The fact that someone who has an illness that they've been told they will have the rest of their lives can have the prospect of being cured from that illness is a tremendous prospect for them.

SOPHIE SCOTT: Stacey suffers from thalassemia. It's an inherited blood disorder where the body produces fewer red blood cells and less haemoglobin than normal - that's the substance in red blood cells that allows them to carry oxygen. It makes her feel tired and short of breath. Untreated, she could die, but Stacey's been given the chance to live a normal life.

She's part of a groundbreaking genetic trial. At the helm is one of Australia's leading genetic scientists, Professor John Rasko.

Gene therapy changes the way patients are treated by correcting the genetic defect that causes their disease, not just treating the symptoms.

This is how it works. Stacey's stem cells are removed. Scientists in the United States insert a healthy copy of the malfunctioning gene into the stem cells. She's given chemotherapy to wipe out her immune system. Then the genetically-modified cells are transplanted back.

It shows a mishmash of abnormal blood cells which are destroyed prematurely instead of normal red blood cells which last four months.

JOHN RASKO, HEAD, ROYAL PRINCE ALFRED HOSPITAL: If you take not a look at a normal slide that I've got prepared, look at how bland...

SOPHIE SCOTT: Much more uniform.

JOHN RASKO: Much more uniform. They all look the same.

SOPHIE SCOTT: So, could Stacey's cells ever look like this that we're seeing here?

JOHN RASKO: Well that's our hope. One day it's possible to imagine that she'll be manufacturing cells in her own body because we've in a sense reset the balance between the haemoglobin production.

SOPHIE SCOTT: Stacey and her fiancé Christian travelled all the way to this medical centre in Chicago for the first part of the procedure.

Her stem cells were harvested from her bone marrow then genetically modified in a lab using a harmless virus.

One month after her trip to the US, the day of the transplant has finally arrived.

SOPHIE SCOTT: Here in the bowels of Sydney's Royal Prince Alfred Hospital, Stacey's new genetically-modified cells have returned from the US. They're taken out of dry ice and thawed.

It's a big moment. Nothing like this has ever been attempted in Australia before. So much could go wrong.

But Stacey's staying optimistic. She's endured chemotherapy to wipe out her bone marrow and is primed to go.

STACEY WONG, THALASSAEMIA PATIENT: Everyone I know is, like, excited and nervous and I'm just like - they're always like, "Are you worried?" I'm like, "Not really. Why would I be worried?"

SOPHIE SCOTT: Drip by drip the genetically-modified cells are slowly infused.

Then, after years of planning, it was over.

JOHN RASKO: Stacey is such a buoyant individual. She's always positive and she's such a joy to look after.

SOPHIE SCOTT: Eight thalassemia patients around the world including Stacey have had the genetically-modified cells infused. Four have been able to reduce or stop blood transfusions completely and it's looking good for Stacey.

JOHN RASKO: We're already seeing the earliest stages of recovery of Stacey's blood. In particular, the white cells are starting to recover and that indicates to us that the bone marrow's starting to work.

SOPHIE SCOTT: Although she's lost her hair due to the chemo, that seems to be the only downside.

STACEY WONG: Now I feel good and going back to work soon, so, yeah, kind of happy - happy it's all over, but just better than I thought I would be.

SOPHIE SCOTT: And she's been able to go for more than a month without a transfusion.

STACEY WONG: But, ever since the treatment, even though my haemoglobin has gone down a little down, like, the blood count, I don't feel that tiredness and that kind of weakness in my muscles.

CHRISTIAN, FIANCE: Now she's got way more energy compared to before she's had this treatment. All those bits and pieces that she couldn't do before, whether it's going out, staying out longer, she can do now.

SOPHIE SCOTT: And they can finally plan the long overseas honeymoon they've dreamed of.

For Stacey, the risks have been worth the reward.

STACEY WONG: I'm glad I said yes and I feel kind of good that I did it.

JOHN RASKO: This is just the beginning of what we hope is going to be a revolution, not just in thalassemia or just blood diseases, but in many different forms of genetic abnormality. And then, hopefully the sky is the limit.

LEIGH SALES: Sophie Scott reporting.

(These are patients in the Bluebird trials).

Thanks Stan .. been following this research  since this article

here is some more info


A recent ABC Report highlighted the first beta-thalassaemia patient to receive gene therapy for this condition in Australia. The patient from Sydney, Stacey Wong aged 26, is one of 8 patients worldwide to have received this breakthrough treatment.

This investigation is part of bluebird bio’s Northstar Study to treat beta-thalassemia major and severe sickle cell disease. This treatment uses a modified virus to deliver the functional human beta-globin gene into patient stem cells ex vivo (out side the body) and then return the modified stem cells to the patient, ideally getting patients to manufacture their own beta-globin.
The company has set up three clinical trials:

1) HGB-204 Study, is a phase 1/2 study designed to evaluate the feasibility, safety and efficacy of LentiGlobin product in the treatment of subjects with beta-thalassemia major. The study is designed to enroll up to 15 patients. Patients will be evaluated for safety and efficacy post-transplant.
2) HGB-205 Study is a phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of subjects with beta-thalassemia major and severe sickle cell disease. The study is designed to enroll up to 7 subjects. In only sickle cell disease patients, efficacy will also be measured based on the number of vaso-occlusive crises or acute chest syndrome events.
3) HGB-206 Study is a phase 1/2 study is designed to evaluate the safety and efficacy of LentiGlobin product in the treatment of severe sickle cell disease in the U.S.
New data presented at the recent American Society of Hematology Annual Meeting in Orlando, Florida, showed the first four patients treated with bluebird bio’s LentiGlobin BB305 therapy remain transfusion-free after at least three months follow up, confirming the functional treatment for the disease. This treatment resulted in sufficient hemoglobin production reducing or eliminating the need for transfusion among beta-thalassemia patients who would otherwise require chronic blood transfusions. These data consisted of the first five patients treated in Bluebird bio’s ongoing Northstar Study and the first three subjects from its earlier study.
LentiGlobin product has so far been well tolerated, the company said in a recent report, with no gene therapy-related serious adverse events observed. The company is now working to complete enrolment in 2015, targeting 22 patients in total. The plans are to start working with experts, patient groups and authorities to map out a regulatory path for the treatment, Chief Medical Officer Dr. David Davidson said.
I have been in contact with Stacey’s doctor in Sydney (Dr. Joy Ho), who is quietly confident about this therapy. While it’s early days for Stacey, it is encouraging to see from the ABC report, that Stacey has recovered from her stem cell transplantation and doing well, but it is too early post-transplant to draw any meaningful conclusions on clinical efficacy. We wish Stacey all the best and hope to see more of Stacey in the near future. Dr Joy has also confirmed that a second Australian patient has now been recruited to the NorthStar clinical study.

Dr. Jim Vadolas, at the Murdoch Children's Research Institute, who is currently studying the LentiGlobin BB305 gene therapy vector in his laboratory, is indeed very excited by this breakthrough treatment. “I’ve been following this technology throughout my career. It has taken over 15 years for beta-thalassaemia gene therapy to reach clinical trials. However, after some initial setbacks in the field, it’s encouraging to see gene therapy finally making significant advances in the clinic.
Although it’s still early days for beta-thalassaemia gene therapy, it’s very important for this treatment to undergo adequate evaluation for safety and efficacy over the next few years. While the future is looking much brighter, it’s important for patients to remain compliant with their recommended treatment and monitoring.

    we believe in you

Posting video of Stacy Wong's Gene Therapy Trial at Royal Prince Alfred Hospital in Australia.

https://www.youtube.com/watch?v=uv86NLamS6c

Some videos on how Gene Therapy Works

https://www.youtube.com/watch?v=MUi94tvclxY
https://www.youtube.com/watch?v=U3RygvuSrok
https://www.youtube.com/watch?v=Ez560GnkSrE
https://www.youtube.com/watch?v=CN61zN8pg8I

The first link, about the current trials is part of the Northstar trials being run by Bluebird Bio. Their results have been great. I just can't imagine how good a patient must feel after being cured.

Thank you Andy.