Using Donor Immune Cells To Mass-Produce CAR-T Autoimmune Therapies

October 7, 2024 by Maya Posch 3 Comments

As exciting as immunotherapies are in terms of fighting cancer, correcting autoimmune disorders and so on, they come with a major disadvantage. Due to the current procedure involving the use of a patient’s own immune (T) cells, this making such therapies rather expensive and involved for the patient. Recent research has therefore focused on answering the question whether T cells from healthy donors could be somehow used instead, with promising results from a recent study on three human patients, as reported in Nature.

The full study results (paywalled) by [Xiaobing Wang] et al. are published in Cell, with the clinical trial details available on the ClinicalTrials.gov website. For this particular trial the goal was to attempt to cure the autoimmune conditions of the three study participants (being necrotizing myopathy (IMNM) and diffuse cutaneous systemic sclerosis (dcSSc)). The T cells used in the study were obtained from a healthy 21-year old woman, and modified with chimeric antigen receptors targeting B (memory) cells. Using CRISPR-Cas9 the T cells were then further modified to prevent the donor cells from attacking the patient’s cells and vice versa.

After injection, the CAR-T cells got to work, multiplying and seeking out the target B cells, including the pathogenic ones underlying the autoimmune conditions. This persisted for a few weeks until the CAR-T cells effectively vanished and new B cells began to emerge, with a clear decrease in autoantibodies. Two months after beginning treatment, all three participants noted marked improvements in their conditions, which persisted at 6 months. For the woman with IMNM, muscle strength had increased dramatically with undetectable autoantibody levels, and the two men with dcSSc saw scar tissue formation reversed and their skin condition improve massively.

It remains to be seen whether this period of remission in these patients is permanent, and whether there any side effects of CAR-T cell therapy. We previously reported on CAR-T cell therapies and the many promises which they hold. Depending on the outcome of these early trials, it could mean that autoimmune conditions, allergies and cancer will soon be worries of the past, marking another massive medical milestone not unlike the invention of vaccines and the discovery of antibiotics.

Reversing Type 1 Diabetes With A Patient’s Own Stem Cells

October 6, 2024 by Maya Posch 8 Comments

Type 1 diabetes is an auto-immune condition whereby the patient’s own immune system attacks the pancreatic islets, destroying them in the process. Since these islets are responsible for producing insulin in response to blood sugar (glucose) levels, the patient is thus required to externally inject insulin for the remainder of their life. That was the expected scenario, but it appears that this form of diabetes may soon be treatable, with one woman now being free of the condition for a year already, as reported in Nature, referencing an article by [Shusen Wang] et al. that describes the treatment and the one-year result.

Most notable with this study is that the researchers didn’t use the regular method to create pluripotent stem cells. These cells were extracted from the patient, to revert back to this earlier developmental stage. They were not modified using genes, but rather singular chemicals (PDF). The advantage of this is that it avoids having to modify the cell’s genomes, which could conceivably cause issues like cancer later on. This was one of the first time that this method was used in a human subject, with islet cells formed and about 1.5 million of them injected into the patient’s abdominal muscles, a novel site for this procedure.

This location made these islets easy to keep track of, and easier to remove in case of any issues compared to the usual injection site within the liver. Fortunately for this woman, no complications occurred and one year later she is still free of any diabetes symptoms. Two other patients in the trial are also seeing very positive results, leaving only the question of whether the auto-immune condition that originally caused the islet destruction still exists. Since this female patient is taking immunosuppressants for a previous liver transplant it’s a hard to thing to judge, especially since we understand the causes behind type 1 diabetes so poorly.

Regardless, this and other trials using pluripotent cells, transplanted islets and more offer the prospect of a permanent treatment for the many people who suffer from type 1 diabetes.

Featured image: “Human induced pluripotent stem cell colony” National Eye Institute/NIH

Little Pharma On The Prairie

September 24, 2024 by Brian McEvoy 53 Comments

Let’s get the obvious out of the way first — in his DEFCON 32 presentation, [Dr. Mixæl Laufer] shared quite a bit of information on how individuals can make and distribute various controlled substances. This cuts out pharmaceutical makers, who have a history of price-gouging and discontinuing recipes that hurt their bottom line. We predict that the comment section will be incendiary, so if your best argument is, “People are going to make bad drugs, so no one should get to have this,” please disconnect your keyboard now. You would not like the responses anyway.

Let’s talk about the device instead of policy because this is an article about an incredible machine that a team of hackers made on their own time and dime. The reactor is a motorized mixing vessel made from a couple of nested Mason jars, surrounded by a water layer fed by hot and cold reservoirs and cycled with water pumps. Your ingredients come from three syringes and three stepper-motor pumps for accurate control. The brains reside inside a printable case with a touchscreen for programming, interaction, and alerts.

It costs around $300 USD to build a MicroLab, and to keep it as accessible as possible, it can be assembled without soldering. Most of the cost goes to a Raspberry Pi and three peristaltic pumps, but if you shop around for the rest of the parts, you can deflate that price tag significantly. The steps are logical, broken up like book chapters, and have many clear pictures and diagrams. If you want to get fancy, there is room to improvise and personalize. We saw many opportunities where someone could swap out components, like power supplies, for something they had lying in a bin or forego the 3D printing for laser-cut boards. The printed pump holders spell “HACK” when you disassemble them, but we would have gone with extruded aluminum to save on filament.

Several times [⁨Mixæl] brings up the point that you do not have to be a chemist to operate this any more than you have to be a mechanic to drive a car. Some of us learned about SMILES (Simplified Molecular Input Line Entry System) from this video, and with that elementary level of chemistry, we feel confident that we could follow a recipe, but maybe for something simple first. We would love to see a starter recipe that combines three sodas at precise ratios to form a color that matches a color swatch, so we know the machine is working correctly; a “calibration cocktail,” if you will.

If you want something else to tickle your chemistry itch, check out our Big Chemistry series or learn how big labs do automated chemistry.

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Apple May Break Into The Hearing Aid Industry

September 17, 2024 by Jenny List 33 Comments

When the entry of a tech giant such as Apple into a market represents its liberation from exploitation, that market must be really broken, yet the reported FDA approval of the hearing aid feature in the latest AirPod earbuds seems to represent just that. The digital hearing aid business is notorious for its sharp sales practices and eye-watering prices, so for all Apple’s own notoriety the news might actually represent a leap forward for consumers in that sector. We have to ask though, if Apple of all people are now the Good Guys, where has the world of electronics gone so badly wrong?

Your grandparents decades ago would have had a simple analogue hearing aid if they had one, usually a small transistor circuit and perhaps with some kind of analogue filtering. Digital aids with DSP algorithms to pick out speech arrived some time in the 1990s, and from there evolved a market in which their high prices increasingly didn’t match the cost of the technology or software involved. At least in the UK, they were sold aggressively to older people as less cumbersome or better than the National Health Service aids, and if you had an older person in the family it was routine to see pages and pages of targeted junk mail offering dubious financial schemes to pay for them.

The question then, given that a modern hearing aid has a relatively cheap microcontroller and DSP at its heart, why has the open source community not risen to the challenge? The answer is that they have, though the Tympan seems an over-expensive trinket for what it is and the LoCHAid and Open Speech Platform seem to have sunk without trace. Can we do better?

Header: Gregory Varnum, CC BY-SA 4.0 .

Hack Your Eyesight With High Tech Bifocals

September 16, 2024 by Al Williams 32 Comments

As we get older, our eyes get worse. That’s just a fact of life. It is a rite of passage the first time you leave the eye doctor with a script for “progressive” lenses which are just fancy bifocals. However, a new high-tech version of bifocals promises you better vision, but with a slight drawback, as [Sherri L. Smith] found.

Remember how users of Google Glass earned the nickname “glassholes?” Well, these new bifocals make Google Glass look like a fashion statement. If you are too young to need them, bifocals account for the fact that your eyes need different kinds of help when you look close up (like soldering) or far away (like at an antenna up on a roof). A true bifocal has two lenses and you quickly learn to look down at anything close up and up to see things far away. Progressives work the same, but they transition between the two settings instead of having a discrete mini lens at the bottom.

The new glasses, the ViXion01 change based on what you are looking for. They measure range and adjust accordingly. For $555, or a monthly rental, you can wear what looks like a prototype for a Star Trek visor and let it deduce what you are looking at and change its lenses accordingly.

Of course, this takes batteries that last about ten hours. It also requires medical approval to be real glasses and it doesn’t have that, yet. Honestly, if they worked well and didn’t look so dorky, the real use case might be allowing your eye doctor to immediately download a new setting as your vision changes. How about you? How much odd headgear are you willing to wear in public and why?

Glasses have a long strange history. While a university prototype we saw earlier was not likely to win fashion awards, they did look better than these. Maybe.

Five colors of Cast21 on five different wrists.

Cast21 Brings Healing Into 2024

September 14, 2024 by Kristina Panos 16 Comments

It takes but an ill-fated second to break a bone, and several long weeks for it to heal in a cast. And even if you have one of those newfangled fiberglass casts, you still can’t get the thing wet, and it’s gonna be itchy under there because your skin can’t breathe. Isn’t it high time for something better?

Enter Cast21, co-founded by Chief Technical Officer [Jason Troutner], who has been in casts more than 50 times due to sports injuries and surgeries. He teamed up with a biomedical design engineer and an electrical engineer to break the norms associated with traditional casts and design a new solution that addresses their drawbacks.

So, how does it work already? The latticework cast is made from a network of silicone tubes that harden once injected with resin and a catalyst mixture. It takes ten seconds to fill the latticework with resin and three minutes for it to cure, and the whole process is much faster than plaster or fiberglass.

This new cast can be used along with electrical stimulation therapy, which can reduce healing time and prevent muscle atrophy.

Cast21 is not only breathable, it’s also waterproof, meaning no more trash bags on your arm to take a shower. The doctor doesn’t even need a saw to remove it, just cut in two places along the seam. It can even be used as a splint afterward.

It’s great to see advancements in simple medical technologies like the cast. And it looks almost as cool as this 3D-printed exoskeleton cast we saw ten years ago.

Thanks to [Keith Olson] for the tip!

Second Human Neuralink Brain Implant Recipient Uses It For CAD And Videogaming

August 22, 2024 by Maya Posch 55 Comments

As Neuralink works towards getting its brain-computer interface technology approved for general use, it now has two human patients who have received the experimental implant. The second patient, [Alex], received the implant in July of 2024 and is said to be doing well, being able to play games like Counter Strike 2 without using his old mouth-operated controller. He’s also creating designs in Fusion 360 to have them 3D printed.

This positive news comes after the first patient ([Noland Arbaugh]) suffered major issues with his implant, with only 10-15% of the electrodes still working after receiving the implant in January. The issue of electrode threads retracting was apparently a known issue years prior already.

We analyzed Neuralink’s claims back in 2019, when its founder – [Elon Musk] – was painting lofty goals for the implant, including reading and writing of brains, integration with AIs and much more. Since that time Neuralink has been mostly in the news for the many test animals which it euthanized during its test campaign prior to embarking on its first human test subjects.

There also appears a continuing issue with transmitting the noisy data from the electrodes, as it is far more data than can be transmitted wirelessly. To solve this seemingly impossible problem, Neuralink has now turned to the public with its Neuralink Compression Challenge to have someone make a miraculous lossless compression algorithm for it.

With still many challenges ahead, it ought to be clear that it will take many more years before Neuralink’s implant is ready for prime-time, but so far at least it seems to at least make life easier for two human patients.

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