More about gene therapy and human gene editing

To my post of last week, add the case of a 44 year-old man who has received gene therapy for an inherited metabolic disease called Hunter’s syndrome. This is another example of a form of gene editing as true therapy.  That is, an existing individual is given a construct intended to edit his genes to introduce a gene that makes an enzyme that is lacking in the disease, and that causes terrible problems.  In this case, as part of a clinical trial, the construct, using a so-called “zinc finger” technique, is intended to introduce the gene into only about 1% of the patient’s liver cells.   If successful, the damage already done by the disease won’t be affected, but it’s progress may be arrested, with the potential to avoid having to have repeated, costly treatment with the missing enzyme protein itself.

Cool idea–and well within the current regulatory ethical regime.  The edit would not be inherited, and unborn humans don’t have to be sacrificed to develop the technique.  The adult patients are capable of giving informed consent.  Trials in children would come later, controlled by accepted ethical experimentation on children in clinical trials.

In a separate note, on a separate topic, Nature Biotechnology is editorializing that inherited gene editing is way behind mitochondrial replacement therapy (MRT), the “3-parent baby” approach to treating genetic problems, and will likely have limited use in the future.  Why?  Because it is likely that preimplantation genetic diagnosis (PGD) after in vitro fertilization (IVF) will be preferred to identify and give birth to babies unaffected by serious genetic disorders.  The journal editors argue that gene editing would be preferred only in those few cases where PGD cannot avoid passing on a disease–for example, in cases where it is known that all embryos from a fertilizing couple would be affected. Otherwise, the gene editing would not be worth the trouble.

MRT, on the other hand, has been studied more and is closer to being used to treat unborn humans who have diseases that MRT could treat.  Thing is, those diseases are also rare, on the order of 1000 cases per year in the US, and technically, gene editing would probably not be too useful for those.

There is a lot of talk about using a mix of gene editing and PGD to eliminate certain genetic disease from the human prospect.  I recently wrote about the Chinese government working on this.  To achieve the goal absolutely, every born human would have to be a product of IVF.

And the risk of some of the disorders is low enough that the absolute risk in any one “natural” pregnancy would be low.  So why go to the trouble of trying to eliminate the risks utterly?  (I think that’s a rhetorical question.)

The title of the editorial in question is “Humans 2.0.”  Indeed.

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Mark McQuainJon HolmlundSteve Phillips Recent comment authors
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Steve Phillips
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The editorial from Nature Biotechnology fits with what I was saying in my post from 8/2/17. Since IVF with PGD is a much simpler and safer way to produce a child without a specific genetic defect, there is no need for germline gene editing to accomplish that for those who would chose to do it. I think that means that the actual use of germline gene editing will be enhancement, even though that is being denied by those developing it.

Jon Holmlund
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Jon Holmlund

excellent point and reminder, Steve, thanks

Mark McQuain
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Mark McQuain

Another example of ethically acceptable in vivo gene therapy is a phase 1 trial at Mayo for adults with moderate knee osteoarthritis. The goal is eventually to get the synovial cells to produce interleukin-1 receptor antagonist to block the effects of interleukin-1 which causes (some of) the inflammation and cartilage breakdown in knee osteoarthritis. The phase 1 trial will test the safety of this technique on a limited number of patients

https://www.mayoclinic.org/medical-professionals/clinical-updates/physical-medicine-rehabilitation/gene-therapy-for-knee-osteoarthritis-q-and-a-with-christopher-h-evans-phd