First gene therapy for Tay-Sachs disease successfully given to two children

This is incredibly moving. It can feel like there&#x27;s no good news in the world, and that techno-optimism isn&#x27;t founded.<p>But these 2 kids are a lot healthier than than they would have been without this incredible invention. This is the kind of stuff we can hold on to.<p>Thanks for sharing.

&quot;The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low.<p>We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. This grassroots approach is a common theme in ultrarare disease research – development and testing are often supported by parents, foundations and federal grants.&quot;<p>FYI - if anyone here is interested in helping these kinds of causes, a company called Orchard Therapeutics provides similar treatments and has just signed a historic agreement for reimbursement for treating MLD patients in Europe (you can read more about it here: <a href="https:&#x2F;&#x2F;www.globenewswire.com&#x2F;news-release&#x2F;2022&#x2F;02&#x2F;04&#x2F;2378990&#x2F;0&#x2F;en&#x2F;Orchard-Therapeutics-Announces-Historic-Agreement-Making-Libmeldy-Available-by-NHS-England-for-MLD-Patients.html" rel="nofollow">https:&#x2F;&#x2F;www.globenewswire.com&#x2F;news-release&#x2F;2022&#x2F;02&#x2F;04&#x2F;237899...</a>).<p>Also big discretion: I do have a lot invested in the company and I have incurred significant losses since deciding to invest in it. In the brilliant world of pyramid schemes vested around crypto-coins and NFTs, I don&#x27;t regret anything and will keep buying more shares to support the dignity of human life.

&gt;We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant.<p>Wish this were not the case.

I don&#x27;t have anything to add except that for some reason, I viscerally remember the first time I heard of Tay-Sachs disease in a high school classroom through a video about genetics.<p>Something made me feel so disturbed about this one disease above all else because of the seeming hopelessness of the situation coupled with the rampant cruelty of how it kills kids from the inside and seemingly reverses developmental progress.<p>I don&#x27;t know why I just remember the moment I learned about this, but this is great news. Hopefully this is the first in many such therapies.

I was a little surprised that the researcher talked only about stopping disease progression, rather than reversal.<p>Especially for the 7-month old. I assumed that at that age, the brain was still growing &#x2F; adapting in ways that could work around the earlier problems.<p>But now that I think about it, I&#x27;ve heard that oxygen deprivation during birth can cause permanent impairment.

This is actually the 2nd brain gene therapy research I&#x27;ve seen.<p>In the Phase I trial below, injecting telomerase and klotho AV vectors into CNS&#x2F;brain was safe and it improved cognitive scores of 5 dementia patients after 1 yr follow up.<p>Interview: <a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=i__oZyxgLC0" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=i__oZyxgLC0</a><p>Paper: <a href="https:&#x2F;&#x2F;www.linkedin.com&#x2F;posts&#x2F;patrick-e-sewell-md-a994774_gene-therapy-for-dementia-activity-6863849206608732160-h9WW&#x2F;" rel="nofollow">https:&#x2F;&#x2F;www.linkedin.com&#x2F;posts&#x2F;patrick-e-sewell-md-a994774_g...</a><p>This space will hopefully get very big. Mice lifespans were extended 25-40% (massive!) through similar techniques. See Dr George Church Gene Therapy for more.

I was actually thinking about Tay-Sachs this morning on a walk, after I passed by a church with a billboard out front that says &quot;Christ died for all, even babies in the womb&quot;.<p>I learned about Tay-Sachs in high school biology. I think we watched a short documentary on it, as an example of genetic inheritance, and the importance of enzyme function. I remember being so surprised that something so simple (absence of one protein) could be so horrible. A beyond-grim prognosis, and immeasurable&#x2F;unavoidable suffering for everyone involved. Since then, it&#x27;s been something that I can&#x27;t reconcile with the existence of a higher benevolent being. I&#x27;m no expert, but it made a lasting impression on me.<p>I&#x27;m so uplifted that researchers have made progress on curing this senseless disease.

Hopefully this is long term successful and the first step in curing a lot of conditions like this.

Can someone explain who this works?<p>&quot;&quot;&quot; I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier. Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions. In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. &quot;&quot;&quot;<p>They use a monkey virus to deliver two mRNA codes to brain cells, the mRNA after being transcribed, tells the brain cells to create HexA to deal with the target enzyme.<p>Okay, I get that much.<p>But how on earth does this work.<p>&quot;&quot;&quot; these DNA instructions enter the nucleus of these cells and stay there &quot;&quot;&quot;<p>I thought mRNA could not alter DNA and it was by definition broken down after use by the cell, ie short term by definition?

Gene therapy is the game-changer which will enable us to eventually cure cancer. I&#x27;ve been proposing that government stop all investment in refining non-gene therapies, such as radiation and chemotherapy, and to plow everything we have into gene-therapy.<p>Cancer is essentially a genetic disease and we can solve it by repairing the faulty genes, just as with Tay Disease.