Unfolding Liz Parrish

[Sthira]

[InquilineKea]

 

Why not do something like combined quercetin + dasatinib? Or combined rapamycin + lithium + trametinib? (and then get blood test results measured by something like Arivale or Metabolon?)

Actually that sounds like a quality self-trial for you, InquilineKea. Why not try a public D/Q experiment (and then get blood test results measured by something like Arivale or Metabolon) and report your stats right here!

 

I'm quite willing, but I don't live in Seattle now, so I can't do Arivale. Also I'm not sure if I have the financial buffers for such an experiment..

 

I might be willing to post all my metabolic data to the Internet (a la David Ewing Duncan/Larry Smarr), if it comes down to it.

 

But continue to encourage/prod me, and it might push me towards finally doing it! :)

[Dean Pomerleau]

Bioviva Files for Dual Gene Therapy Patent

 

Liz Parrish is at it again. After reporting a couple months ago that her leukocyte telomeres got longer, she and her company have gone ahead and filed for a patent on the two gene therapy treatments she underwent. Here is the press release on the patent filing. The patent describes “a method of treating or preventing age-related disorders in a subject by administering to the subject a therapeutically effective amount of a human Telomerase Reverse Transcriptase (hTERT) gene in combination with a Follistatin gene.”

 

She/Bioviva claims that they are filing for the patent to "keep anti-aging gene therapy affordable", elaborating as follows:

 

There are many reasons to patent: to lock rival companies out of a technology and to create revenue from licensing, but another is to ensure access to technologies by precluding rivals from monopolising.

 

So her motivation for patenting may be quite noble and genuine. But I can't help but noting that earlier this year Bioviva became a portfolio company of Deep Knowledge Life Sciences, a London-based investment fund. Call me a skeptic/cynic, but presumably money changed hands as part of that transaction, and so at some point the bean counters will likely come knocking on Liz's door. We'll see then just how altruistic their plans remain.

 

--Dean

[Sthira]

Maybd gene editing trials will progress more rapidly than originally thought, thus rendering Parrish's attempts irrelevant.

 

For example:

 

https://www.newscientist.com/article/2094832-first-human-crispr-trial-given-go-ahead-your-questions-answered/

 

By Michael Le Page

 

The CRISPR gene editing revolution is happening even faster than we expected. Many thought human trials of therapies using the technique were still years away. But yesterday, a US federal committee gave its nod of approval – meaning the first trial could start later this year. The therapy is designed to treat cancer but the main purpose of this first trial is safety. If it succeeds, it will encourage many other groups to start testing treatments that involve CRISPR.

 

What does the trial involve?

 

Immune cells called T-cells will be taken from people with specific forms of three kinds of tumours – melanoma, sarcoma and myeloma. An entirely new gene will be added to these T-cells, for a receptor that binds to a protein called NY‐ES0‐1, which is found on many kinds of tumour cells.

 

Equipped with this new receptor, the T-cells will seek out and destroy tumour cells.

 

Many reports state that the gene for this new T-cell receptor will be added using CRISPR genome editing, but this is not the case. In fact, a harmless virus will be used to add the gene.

 

CRISPR, on the other hand, will be used to destroy the existing T-cell receptor to make the altered cells focus on targeting tumours instead of targeting other bits of foreign DNA or viruses. Since two genes code for this receptor, this involves disabling two genes.

 

CRISPR will also be used to disable PD1 – an off-switch that sits on the outside of T-cells. Many cancers evolve the ability to use this switch to turn off PD1 and block their attacks.

 

Finally, the engineered cells will be infused back into the patient’s blood.

 

So the cells put back in the patients will have four changes in total, three involving CRISPR?

 

Well, some of them will. Because the modification process does not work every time, the T-cells put back into the patients will actually be a mix of cells with various combinations of these changes. Only 3 or 4 per cent may have all four changes.

 

Is this the first time T-cells have been engineered to target cancers?

 

Far from it. Trials of T-cells with an added receptor gene to make them target cancers have been going on for several years now. They have proved very effective in treating blood cancers such as leukaemia, completely curing people in some cases. However, they have not worked for solid tumours such as sarcomas and melanomas. The hope is that disabling genes such as PD1 will make them more effective against solid tumours.

 

This approach is often called CAR T-cell therapy, because the T-cell receptor added to the immune cells is of a kind known as a chimeric antigen receptor. However, a different type of receptor will be added in the CRISPR trial, so technically this is not a CAR T-cell therapy although the principle is the same.

 

Will this trial be the first time gene editing has been used in addition to adding a T-cell receptor?

 

No, older methods of gene editing have been used to knock out genes in CAR T-cells. This approach was used last year to treat a girl called Layla. She was so sick that no T-cells could be taken from her to be turned into CAR T-cells.

 

Instead, doctors used a gene editing technique called TALEN to disable the protein that marks T-cells as belonging to the self or other, allowing donor cells to be used to treat her.

 

Within a month, no more cancerous cells could be found, though it will be another year or two before it is clear whether Layla is completely cancer free.

 

The TALEN method works well, but it can take years to develop specific treatments. CRISPR takes just weeks, so if it proves safe, it will become much easier and cheaper to develop new T-cell therapies.

 

What is the main safety concern?

 

All gene editing methods work by cutting DNA but sometimes they cut DNA in the wrong place. In theory, this could turn the T-cells cancerous by introducing cancer-causing mutations, but no signs of any abnormalities have been seen when the modified T-cells are grown in culture. The next step is to test them in people – hence this safety trial.

 

Will this safety trial be the first ever human trial of CRISPR?

 

Probably. The trial still needs to get approval from the hospitals and universities involved, but this is likely to be a formality now the National Institutes of Health’s Recombinant DNA Advisory Committee has given the go-ahead.

 

A company called Editas Medicine in Cambridge, Massachusetts, has said it wants to start human trials of CRISPR for treating a rare form of blindness in 2017, but it has not yet applied to the committee.

 

If another case similar to Layla’s comes up, though, doctors might decide to use CRISPR-edited cells before the safety trial begins. Layla’s treatment was not given as part of a clinical trial, but as a last resort after all other treatments had failed.

[Dean Pomerleau]

All,

 

A new article in the Guardian which is on the whole pretty critical of Liz Parrish's N-of-1 experiment. It quotes a bunch of researchers in the aging field, including some of her advisors, who don't think she's gone about it the right way. But heh, as Sthira points out, at least she's doing something and taking the bull by the horns. Got to admire her for that, in my book.

 

--Dean