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by iamleppert 2777 days ago
I was recently one of the first recipients of gene therapy for my condition. I have Hemophilia A, which is a bleeding disorder that results in bleeding into joints, muscle and soft tissue due to lack of a naturally occurring clotting factor that my body can't produce due to a defective gene. I received my dose of 30 billion viral particles about 13 weeks ago as part of a phase II clinical trial at UCSF.

It is amazing to me that we can manufacture and program viral particles to target specific cells. In my case, my treatment is a non-nucleonic technique that didn't repair the actual chromosomal hereditary defect but inserted a working gene, additional and freely available genetic material into my liver cells. It's amazing that the body can just recognize this extra bit of code and just start producing the factor. The engineer in me is also impressed they can make so many copies of the engineered virus.

It appears to be working. My factor levels have steadily increased and I’m now no longer a severe or even moderate hemophiliac. I’m their first patient to have achieved these results for hemophilia A severe and it puts me well into the therapeutic range. It really feels like I have been given a new body, it’s indescribable. For the first time in my life, I’m pain free.

It’s a weird feeling. Pain, mostly from bleeds into my joints, has been my constant companion. I was never able to do sports as a kid and had to avoid many other activities that would put me at risk. I have mixed feelings about all of this. On one hand I’m extraordinarily grateful, and the other side I see what a huge disadvantage I’ve been at compared to others for all of my life. I thought this day would never come, I had resigned myself to my limitations but now they are gone in a matter of weeks through the miracle of a medical experiment.

My old medication, a replacement clotting factor that was synthetically produced in a lab, worked but not nearly as well as this. Not to mention the fact it cost over $100,000 per month and I had to give myself an IV every other day. It's truly been a life changing experience for me, and I hope that gene therapy becomes widely available to others.

Also, the thing that was a milestone in this case was that the Hemophilia A factor VIII gene has been notoriously difficult to create a genetic therapy for because of the complexity of the actual gene itself. On the scale of what the body produces, its one of the more complicated proteins. So it basically means many other genetic conditions will be able to be treated with and addressed with similar technology.

Such an exciting time to be alive, and yes there are amazing things happening right now despite all the bad news you may hear!

3 comments

Thank you for sharing. My first undergrad studies were a double major in Science (Chemistry/Biology) 12 years ago and yet I had zero clue that we were at the stage currently to do what you described. To hear what you've just described is absolute music to my ears and it makes me very happy. While you may have lived a number of years dealing with your issues it means that we are likely approaching a time when children will be able to be cured early and live pain-free lives.
You’re welcome and yes I agree about this being most impactful for children. Hemophilia had a big effect on my life, both physically and psychologically, as well as my family. It’s hard to grow up knowing you’re so different from others. Now, someone born with hemophilia may never even have to know. It changes things dramatically.

In a single generation we’ve gone from being able to treat the condition at all (replacement factor was just becoming available when I was born) to being able to completely cure it.

a next step would be for the virus to fix the cells from which the gametes derive, then your future offspring would be cured as well
Delighted for you. I feel we're truly on the cusp of a revolution in medical understanding. We've been stabbing in the dark with destructive systemic treatments until now.
Did you need immunosuppressive treatment?
Nope, and I didn’t have any noticeable immune response. Literally no side effects to speak of, it was all very easy, just a simple injection and overnight stay in the hospital for monitoring.

They tested me before for immunity to the virus family they engineered, to make sure I didn’t already have immunity.

Other than that they are monitoring my liver closely but there hasn’t been any elevation in blood tests or structural changes (observed via MRI).

The hell with bioethics hand-wringers... we should be mending and improving people's genes whenever and wherever we can add net good.
not all "bioetchics hand-wringers" are against gene therapy ( in fact you too are taking a bioethical stance).

bio-ethicists aren't only interested in the net good of the patient of the therapy, but also in any harms onto others: perhaps child victims of organ trade (for example sourcing fibroblast stem cells from unnecessary circumcision of infants), perhaps harvesting organs from political, cultural or criminal prisoners, or from refugees, and yes, some of them are worried about viruses ...

How was the recovery process? Did you feel better immediately or was it in small amounts and over several weeks?
There was no recovery process to speak of in a traditional sense. Since this is a chronic condition, I’ve just simply gotten used to the aches and pains over the years. I really didn’t start to feel any different until a few weeks ago, when I realized I had forgotten to take my pain and arthritis mediciation, but I wasn’t having any pain that day. I went off it and I haven’t had to go back on it. My joints all feel noticeably better, there’s basically no pain anymore when I walk. I’d have some days like this before but nothing this long sustained before.

It’s too early to tell but my doctors think that with a sustained factor level, my body isn’t under as much stress from the bleeding all the time and can focus on repairing the damage caused from a lifetime of near constant bleeding.

That's awesome to hear. I'm so very happy for you. Looking forward to a world where these gene therapy solutions are available to more and more people for a wider range of illnesses.