Posts with «tests & procedures» label

CRISPR-based gene editing therapy approved by the FDA for the first time

In a landmark decision, the FDA greenlit two new drugs for the treatment of sickle cell disease in patients 12 and older, one of which —Vertex’s drug Casgevy — is the first approved use of genome editing technology CRISPR in the US. Bluebird Bio’s Lyfgenia also is a cell-based gene therapy, however, it uses a different gene modification technique to deliver tweaked stem cells to the patient.

Both approvals cultivate new pathways for the treatment of sickle cell disease, which is an inherited blood disorder that is characterized by red blood cells that can’t properly carry oxygen, which leads to painful vaso-occlusive crises (VOCs) and organ damage. The disease is particularly common among African Americans and, to a lesser extent, among Hispanic Americans. Bone marrow transplants are currently the only cure for sickle cell disease, but they require well-matched donors and often involve complications.

#Breaking: The U.S. FDA approves our treatment for #SickleCellDisease. We are excited to make this treatment available to patients. Learn more:

— Vertex Pharmaceuticals (@VertexPharma) December 8, 2023

While both drug approvals use gene editing techniques, Casgevy’s CRISPR/Cas9 genome editing works by cutting out or splicing in DNA in select areas. Patients first have blood drawn so that their own stem cells can be isolated and edited with CRISPR. They then undergo a form of chemotherapy to remove some bone marrow cells, so the edited stem cells can be transplanted back in a single infusion.

Both drug approvals are based on studies that evaluated the effectiveness and safety of the novel therapies in clinical patients. With Casgevy, study participants reported that they did not experience “severe VOCs” for at least 12 consecutive months during the 24-month follow-up. Similarly, patients on Lyfgenia did not experience a “pain crisis” for six to 18 months after the therapy.

The FDA's decision comes shortly after UK regulators, as well as the National Health Regulatory Authority in Bahrain both approved Vertex’s Casgevy. The approval for a CRISPR-based treatment creates opportunity for further innovation in the gene editing space — for treatments ranging from cancers to heart diseases to Alzheimer’s. “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” Nicole Verdun, director of the Office of Therapeutic Products at the FDA’s Center for Biologics Evaluation and Research said. Casgevy is still currently under review by the European Medicines Agency.

This article originally appeared on Engadget at

UK authorizes first gene therapy for treating sickle cell disease

In a landmark decision, the UK’s Medicines and Healthcare products Agency (MHRA) approved the use of a gene-editing therapy called Casgevy for patients with sickle cell disease and beta thalassemia — both of which are hereditary disorders related to genetic mutations of the red blood cells. The treatment, manufactured by Vertex, is the first-ever approved therapy that utilizes CRISPR-based gene editing technology to treat eligible patients.

The UK approval of the novel therapy is informed by two previous global clinical trials that indicated the treatment's efficacy. 97 percent of patients using Casgevy were relieved of severe pain associated with the blood disorders for at least 12 months after treatment during the trials. The results suggest that the gene editing treatment could replace the current standard for care. Stem cell therapy and bone marrow transplants are currently the only pathways to cure sickle cell disease and beta thalassemia, however, they involve a lot of risks.

Both sickle cell disease and beta thalassemia are blood disorders characterized by defective red blood cells that can’t carry oxygen, and require patients to get monthly blood transfusions that can be costly and time-consuming. Casgevy works by specifically targeting the genes in the bone marrow stem cells that produce faulty blood cells. For the treatment to work, a patient’s stem cells need to be extracted from their bone marrow, edited in a lab and then re-infused into the patient.

#Breaking: The UK Medicines and Healthcare products Regulatory Agency (MHRA) approves our CRISPR/Cas9 gene-edited treatment for #SickleCellDisease and #BetaThalassemia in Great Britain—a historic scientific milestone. Learn more:

— Vertex Pharmaceuticals (@VertexPharma) November 16, 2023

Despite its promising outlook, CRISPR-based therapies may not be easily available to the general public. Gene editing is an expensive endeavor. The Innovative Genomics Institute (IGI) estimates that the average CRISPR-based therapy will cost between $500,000 and $2 million per patient. The IGI has built out an ‘Affordability Task Force’ to tackle the issue of expanding access to these novel therapies.

Aside from costliness, gene editing therapies offer huge promise to innovate treatment pathways for rare conditions including neurodegenerative diseases, cancer and muscular atrophy. More importantly, this landmark approval for Casgevy “opens the door for further applications of CRISPR therapies in the future,” Prof Dame Kay Davies, a scientist from the University of Oxford, said. And new iterations of gene editing technologies may even surpass CRISPR in the future.

Casgevy is still being reviewed by regulatory agencies for safety standards in other countries, including the United States and Saudi Arabia. A marketing application, the first step towards approval for the therapy, was recently validated by the European Medicines Agency.

This article originally appeared on Engadget at

An experimental rice-sized implant monitors how drugs affect tumors

Researchers at Brigham and Women’s Hospital in Boston have developed an implant, notably as small as a grain of rice, that can test the effects of drugs on a patient’s brain tumor in real-time during surgery. Currently, monitoring the effects of drugs on a brain cancer patient during surgery is limited to intraoperative brain imaging and tissue sampling after a drug has been administered. The technique known as microdialysis currently stands as one of the more minimally invasive sampling options for testing the impact of drugs on brain tumors, but even that requires an entire catheter to be inserted into the patient’s skull cavity.

During development, researchers from Brigham and Women’s Hospital designed the device specifically to help test treatments in patients with brain cancers or gliomas, a type of tumor that originates in the brain or spinal cord. The device is designed to only remain implanted in a patient for about two to three hours while it delivers microdoses of the respective drug that is under observation. It can observe the impact of up to 20 drugs on the market for cancerous tumors, according to the researchers. Once the device is removed (sometime before the surgery ends), the surrounding tissue is returned to the lab for analysis.

In a statement published Wednesday, Pierpaolo Peruzzi, co-principal investigator and assistant professor in the Department of Neurosurgery at Brigham and Women’s Hospital said that knowing the impact of cancer drugs on these tumors is critical. “We need to be able to understand, early on, which drug works best for any given patient,” he said.

Brigham and Women’s Hospital

During the development process, researchers at the Brigham and Women’s Hospital ran a clinical trial to observe the actual impact of the implant on real patients. The study found that none of the patients in the trial experienced any adverse effects. The researchers were able to collect biological data from the devices, such as what molecular changes happened when each drug was administered. While the study demonstrated that the implant could be easily incorporated into surgical practice, the researchers are still determining how the data it can gather should be used to optimize tumor therapy.

The researchers are now conducting another study that focuses on implanting the device through a minimally invasive procedure 72 hours before their main surgery. Advancements in the cancer treatment space continue to expand, with new iterations of drug cocktails and viruses that can fight cancer cells emerging in the biotech space. Implants like the one developed by the Brigham and Women’s Hospital bring scientists one step closer to better being able to use tools and data to provide more personalized care treatment plans for cancer patients.

This article originally appeared on Engadget at

Biometric implant monitors transplant patients for organ rejection

Researchers at Northwestern University developed a bioelectric implant that can detect temperature fluctuations that typically happen right before a body rejects an organ transplant. The sensor is smaller than a fingernail, and a mere 220 micrometers thick.

This new sensor technology is thin enough to sit directly on a kidney's fibrous layer — called the renal capsule — which surrounds and protects the organ. The device works by continuously monitoring changes to blood flow and temperature. The built-in thermometer can sense increases as minuscule as 0.004 degrees Celsius. Once an irregularity is detected, the sensor, which contains a micro coin cell battery for power, uses Bluetooth to alert a patient or physician via a smartphone or tablet. Any increase typically signals inflammation which is a potential sign of transplant rejection.

After any surgery that involves an organ transplant, the risk of rejection is high. The sensor was developed specifically for kidney transplants but it could also work for other organs, including the liver and lungs. Kidney transplants in the US are on the rise and are usually recommended for people who will not be able to live without dialysis. The American Kidney Fund cites that an acute rejection of a kidney transplant one month after surgery happens in about five to twenty percent of patients that go under.

That’s why it is critical to detect transplant rejection, which occurs when your body's immune system treats the new organ like a foreign object and attacks it. If a healthcare provider detects signs of rejection early enough, medical intervention can preserve the new organ in the new host. Northwestern researchers said that the device detected warning signs of organ rejection three weeks earlier than current monitoring methods. The current “gold standard” for detecting rejection is a biopsy, where a tissue sample is extracted from the transplanted organ and then analyzed in a lab. However, biopsies are invasive and can cause bleeding and increase the risk for infection.

Northwestern University

Despite developing an innovative first-of-its-kind product, researchers at Northwestern University still have a long way to go. It still needs to be tested on humans in a clinical setting before it can make any impact in the surgical market. Northwestern’s John A. Rogers, a bioelectronics expert who led the device development, said in a statement that his team is now evaluating ways to recharge the coin cell battery so that it can last a lifetime.

This article originally appeared on Engadget at

Synchron's BCI implants may help paralyzed patients reconnect with the world

Dr. Tom Oxley visibly stiffens at the prospect of using brain-computer interface technology for something as gauche as augmenting able-bodied humans. “We're not building a BCI to control Spotify or to watch Netflix,” the CEO of medical device startup Synchron tersely told Engadget via videocall last week.

“There's all this hype and excitement about BCI, about where it might go,” Oxley continued. “But the reality is, what's it gonna do for patients? We describe this problem for patients, not around wanting to super-augment their brain or body, but wanting to restore the fundamental agency and autonomy that [able-bodied people] take for granted.”

Around 31,000 Americans currently live with Amyotrophic lateral sclerosis (ALS) with another 5,000 diagnosed every year. Nearly 300,000 Americans suffer from spinal cord paralysis, and another approximately 18,000 people join those ranks annually. Thousands more are paralyzed by stroke and accident, losing their ability to see, hear or feel the world around them. And with the lack of motor control in their extremities, these Americans can also lose access to a critical component of modern life: their smartphone.

“[A smartphone] creates our independence and our autonomy,” Oxley said. “It's communicating to each other, text messaging, emailing. It's controlling the lights in your house, doing your banking, doing your shopping, all those things.”

“If you can control your phone again,” he said. “you can restore those elements of your lifestyle.”

So while Elon Musk promises an fantastical cyberpunk future where everybody knows Kung Fu and can upload their consciousness to the cloud on a whim, startups like Synchron, as well as Medtronic, Blackrock Neurotech, BrainGate and Precision Neuroscience and countless academic research teams, are working to put this transformative medical technology into clinical practice, reliably and ethically.

The Best Way to a Man’s Mind Is Through His Jugular Vein

Brooklyn-based Synchron made history in 2022 when it became the first company to successfully implant a BCI into a human patient as part of its pioneering SWITCH study performed in partnership with Mount Sinai Hospital. To date, the medical community has generally had just two options in capturing the myriad electrical signals that our brains produce: low-fidelity but non-invasive EEG wave caps, or high-fidelity Utah Array neural probes that require open-brain surgery to install.

Synchron’s Stentrode device provides a third: it is surgically guided up through a patient’s jugular vein to rest within a large blood vessel near their motor cortex where its integrated array of sensors yield better-fidelity signal than an EEG cap without the messy implantation or eventual performance drop off of probe arrays.

“We're not putting penetrative electronics into the brain and so the surgical procedure itself is minimally invasive,” Dr. David Putrino, Director of Rehabilitation Innovation for the Mount Sinai Health System, explained to Engadget. “The second piece of it is, you're not asking a neurologist to learn anything new ... They know how to place stents, and you're really asking to place a stent in a big vessel — it's not a hard task.”

“These types of vascular surgeries in the brain are commonly performed,” said Dr. Zoran Nenadić, William J. Link Chair and Professor of Biomedical Engineering at the University of California, Irvine. “I think they're clever using this route to deliver these implants into the human brain, which otherwise is an invasive surgery.”

Though the Stentrode’s signal quality is not quite on par with a probe array, it doesn’t suffer the signal degradation that arrays do. Quite the opposite, in fact. “When you use penetrative electrodes and you put them in the brain,” Putrino said, “gliosis forms around the electrodes and impedances change, signal quality goes down, you lose certain electrodes. In this case, as the electrode vascularizes into the blood vessel, it actually stabilizes and improves the recording over time.”

A Device for Those Silent Moments of Terror

“We're finally, actually, paying attention to a subset of individuals with disabilities who previously have not had technology available that gives them digital autonomy,” Putrino said. He points out that for many severely paralyzed people, folks who can perhaps wiggle a finger or toe, or who can use eye tracking technology, the communication devices at their disposal are situational at best. Alert buttons can shift out of reach, eye tracking systems are largely stationary tools and unusable in cars.

“We communicate with these folks on a regular basis and the fears that are brought up that this technology can help with,” Putrino recalls. “It is exactly in these silent moments, where it's like, the eye tracking has been put away for the night and then you start to choke, how do you call someone in? Your call button or your communication device is pushed to the side and you see the nurse starting to prepare the wrong medication for you. How do you alert them? These moments happen often in a disabled person's life and we don't have an answer for these things.”

With a BCI, he continued, locked-in patients are no longer isolated. They can simply wake their digital device from sleep mode and use it to alert caregivers. ”This thing works outside, it works in different light settings, it works regardless of whether you're laying flat on your back or sitting up in your chair,” Putrino said. “Versatile, continuous digital control is the goal.”

Reaching that goal is still at least half a decade away. “Our goal over the next five years is to get market approval and then we’ll be ready to scale up that point,” Oxley said. The rate of that scaling will depend on the company’s access to cath labs. These are facilities found in both primary and secondary level hospitals so there are thousands of them around the country, Oxley said. Far more than the handful of primary level hospitals that are equipped to handle open-brain BCI implantation surgeries.

A Show of Hands for Another Hole in Your Head

In 2021, Synchron conducted its SWITCH safety study for the Stentrode device itself, implanting it in four ALS patients and monitoring their health over the course of the next year. The study found the device to be “safe, with no serious adverse events that led to disability or death,” according to a 2022 press release. The Stentrod “stayed in place for all four patients and the blood vessel in which the device was implanted remained open.”

Buoyed by that success, Synchon launched its headline-grabbing COMMAND study last year, which uses the company’s entire system in six patients to help them communicate digitally. “We’re really trying to show that this thing improves quality of life and improves agency of the individual,” Putrino said. The team had initially expected the recruitment process through which candidate patients are screened, to take five full years to complete.

Dr. Putrino was not prepared for the outpouring of interest, especially given the permanent nature of these tests and quality of life that patients might expect to have once they're in. “Many of our patients have end-stage ALS, so being part of a trial is a non-trivial decision,” Putrino said. “That's like, do you want to spend what maybe some of the last years of your life with researchers as opposed to with family members?”

“Is that a choice you want to make for folks who are considering the trial who have a spinal cord injury?” asked Putrino, as those folks are also eligible for implantation. “We have very candid conversations with them around, look, this is a gen one device,” he warns. “Do you want to wait for gen five because you don't have a short life expectancy, you could live another 30 years. This is a permanent implant.”

Still, the public interest in Synchron’s BCI work has led to such a glut of interested patients, that the team was able to perform its implantation surgery on the sixth and final patient of the study in early August — nearly 18 months ahead of schedule. The team will need to continue the study for at least another year (to meet minimum safety standards like in the previous SWITCH study) but has already gotten permission from the NIH to extend its observation portion to the full original five years. This will give Synchron significantly more data to work with in the future, Putrino explained.

How We Can Avoid Another Argus II SNAFU

Our Geordi LaForge visor future seemed a veritable lock in 2013, when Second Sight Medical Products received an FDA Humanitarian Use Device designation for its Argus II retinal prosthesis, two years after it received commercial clearance in Europe. The medical device, designed to restore at least rudimentary functional vision to people suffering profound vision loss from retinitis pigmentosa, was implanted in the patient’s retina and converted digital video signals it received from an external, glasses-mounted camera into the analog electrical impulses that the brain can comprehend — effectively bypassing the diseased portions of the patient’s ocular system.

With the technical blessing of the FDA in hand (Humanitarian Use cases are not subject to nearly the same scrutiny as full FDA approval), Second Sight filed for IPO in 2013 and was listed in NASDAQ the following year. Seven years after that, the company went belly up in 2020, declared itself out of business and wished the best of luck to the suckers who spent $150k to get its hardware hardwired into their skulls.

“Once you're in that [Humanitarian Use] category, it's kind of hard to go back and do all of the studies that are necessary to get the traditional FDA approvals to move forward,” Dr. An Do, Assistant Professor in the Department of Neurology at University of California, Irvine, told Engadget. “I think the other issue is that these are orphan diseases. There's a very small group of people that they're catering to.”

As IEEE Spectrum rightfully points out, one loose wire, one degraded connection or faulty lead, and these patients can potentially re-lose what little sight they had regained. There’s also the chance that the implant, without regular upkeep, eventually causes an infection or interferes with other medical procedures, requiring a costly, invasive surgery to remove.

“I am constantly concerned about this,” Putrino admitted. “This is a question that keeps me up at night. I think that, obviously, we need to make sure that companies can in good faith proceed to the next stage of their work as a company before they begin any clinical trials.”

He also calls on the FDA to expand its evaluations of BCI companies to potentially include examining the applicant’s ongoing financial stability. “I think that this is definitely a consideration that we need to think about because we don't want to implant patients and then have them just lose this technology.”

“We always talk to our patients as we're recruiting them about the fact that this is a permanent implant,” Putrino continued. “We make a commitment to them that they can always come to us for device related questions, even outside the scope of the clinical trial.”

But Putrino admits that even with the best intentions, companies simply cannot guarantee their customers of continued commercial success. “I don't really know how we safeguard against the complete failure of a company,” he said. “This is just one of the risks that people are going to take coming in. It's a complex issue and it's one I worry about because we're right here on the bleeding edge and it's unclear if we have good answers to this once the technology goes beyond clinical trials.”

Luckily, the FDA does. As one agency official explained to Engadget, “the FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority.” Should a company go under, file bankruptcy or otherwise be unable to provide the services it previously sold, in addition to potentially being ordered by the court to continue care for its existing patients, “the FDA may also take steps to protect patients in these circumstances. For example, the FDA may communicate to the public, recommendations for actions that health care providers and patients should take.”

The FDA official also notes that the evaluation process itself involves establishing whether an applicant “demonstrates reasonable assurance of safety and effectiveness of the device when used as intended in its environment of use for its expected life … FDA requirements apply to devices regardless of a firm’s decision to stop selling and distributing the device.”

The Synchron Switch BCI, for its part, is made from biologically inert materials that will eventually be reabsorbed into the body, “so even if Synchron disappeared tomorrow, the Switch BCI is designed to safely remain in the patient’s body indefinitely,” Oxley said. “The BCI runs on a software platform that is designed for stability and independent use, so patients can use the platform without our direct involvement.”

However, this approach “is not sufficient and that, given BCIs’ potential influence on individuals and society, the nature of what is safe and effective and the balance between risk and benefit require special consideration,” argued a 2021 op-ed in the AMA Journal of Ethics. “The line between therapy and enhancement for BCIs is difficult to draw precisely. Therapeutic devices function to correct or compensate for some disease state, thereby restoring one to ‘normality’ or the standard species-typical form.” But what, and more importantly who, gets to define normality? How far below the mean IQ can you get before forcibly raising your score through BCI implantation is deemed worthwhile to society?

The op-ed’s authors concede that “While BCIs raise multiple ethical concerns, such as how to define personhood, respect for autonomy, and adequacy of informed consent, not all ethical issues justifiably form the basis of government regulation.” The FDA’s job is to test devices for safety and efficacy, not equality, after all. As such the authors instead argue that, “a new committee or regulatory body with humanistic aims, including the concerns of both individuals and society, ought to be legislated at the federal level in order to assist in regulating the nature, scope, and use of these devices.”

This article originally appeared on Engadget at

Johnson & Johnson gets FDA approval for heart treatments that don't require X-rays

Johnson & Johnson's Medical technology arm received FDA approval for a new workflow that will make it safer for medical professionals to treat atrial fibrillation, a condition that makes your heartbeat irregular and can cause stroke or heart failure. Several products developed by Biosense Webster, which is part of J&J MedTech, got the OK for a "zero fluoroscopy workflow" from the FDA, meaning live X-ray imaging will no longer be needed during catheter insertion procedures. Instead of using X-rays to insert Biosense catheters, medical professionals can now use ultrasound to guide treatments.

Using fewer X-rays, or fluoroscopy, lowers radiation exposure for both patients and medical professionals. Currently, doctors and medical staff who work in treatment rooms that specialize in treating relevant heart procedures often get too much exposure to radiation over time, which can lead to problems like eye issues, cancer, and bone injuries. This FDA approval helps address the recurring occupational hazard. Providers working in cath labs also won't have to wear heavy protective gear like lead aprons anymore when applying the newly approved workflow, reducing the risk of long-term muscle and bone pain.

This move by the FDA marks the first and only approval of its kind. The thumbs up was based on data from clinical trials and research from the REAL AF Registry, or the real-world evidence registry in the electrophysiology field. The data backed how well the treatment works in real-life situations. The new method will only apply for Biosense products like the THERMOCOOL SMARTTOUCH SF catheter, the most commonly used ablation catheter, among others.

This article originally appeared on Engadget at

Researchers develop blood test that can reliably detect Alzheimer’s disease

When doctors need to confirm an Alzheimer's diagnosis, they often turn to a combination of brain imaging and cell analysis. Both have their downsides. The latter involves a lumbar puncture, an invasive and painful procedure that’s more commonly known as a spinal tap. A doctor will insert a needle into the lower back to extract a sample of the patient’s cerebrospinal fluid. A lab technician then tests the sample for signs of progressive nerve cell loss and excessive amyloid and tau protein accumulation. MRI scans are less invasive but they’re often expensive and accessibility is an issue; not every community has access to the technology.

The next best tool for diagnosing Alzheimer’s disease is a blood test. While some can detect abnormal tau protein counts, they’re less effective at spotting the telltale signs of neurodegeneration. But that could soon change. This week, in the journal Brain, a multinational team made up of researchers from Sweden, Italy, the UK and US detailed a new antibody-based blood test they recently developed. The new test can detect brain-derived tau proteins, which are specific to Alzheimer’s disease. Following a study of 600 patients, the team found their test could reliably distinguish the illness from other neurodegenerative diseases.

Dr. Thomas Karikari, a professor of psychiatry at the University of Pittsburgh and one of the co-authors of the study, told The Guardian he hopes the breakthrough could help other researchers design better clinical trials for Alzheimer’s treatments. “A blood test is cheaper, safer and easier to administer, and it can improve clinical confidence in diagnosing Alzheimer’s and selecting participants for clinical trial and disease monitoring,” he said. There’s more work to be done before the test makes its way to your local hospital. To start, the team needs to validate that it works for a wide variety of patients, including those who come from different ethnic backgrounds.

The cutting-edge cellular therapies aiming to ease America's organ shortage

Despite being the wealthiest nation on the face of the planet, the United States chronically runs short of transplantable organs. Kidneys are far and away the most sought-after organ for transplantation, followed by livers. While the liver is the only human organ known capable of regenerating itself, if you damage yours badly enough for long enough — as some 30 million Americans have — then the only treatment is a transplant. Assuming you can even acquire one for doctors to stick in you. Every year demand for replacement livers outstrips supply by a scope of tens of thousands.

“Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23 percent in the next 20 years,” a multidisciplinary team of researchers observed in 2016’s Liver-Regenerative Transplantation: Regrow and Reset. “Exacerbating the organ shortage problem, the donor pool is expected to shrink further because of the obesity epidemic. Liver steatosis [aka fatty liver disease] is increasingly common in donors and is a significant risk factor in liver transplantation.”

To address this critical shortage, the study authors note that doctors have explored a variety of cutting-edge regimens, from cell repopulation and tissue engineering, nanoparticles to genomics, mechanical aids to porcine-derived xenotransplantation, all with varying degrees of success. Cellular repopulation has been used for years, a process that injects healthy liver cells into the patient’s damaged organ through a portal vein where they adhere themselves to the existing cellular scaffolding and grow into new, functional liver tissue.

Fabian Bimmer / reuters

“Creating an immediately available and inexhaustible supply of functioning liver cells from autologous tissue would allow early intervention in patients with hepatic failure and would allow liver cells to be infused over a longer period of time,” the 2016 study’s authors note. “Combined with recent advances in genome-editing technology, such liver cells could be used widely to treat devastating liver-based inborn errors of metabolism and to eliminate the need for a life-long regimen of immunosuppressive drugs and their complications.” The downside to this technique is the pace at which the donor cells proliferate, making it a poor tool against acute liver failure.

Extracellular Vesicle-based therapies, on the other hand, leverage the body’s intracellular communications pathways to deliver drugs with, “high bioavailability, exceptional biocompatibility, and low immunogenicity,” according to 2020’s Extracellular Vesicle-Based Therapeutics: Preclinical and Clinical Investigations. “They provide a means for intercellular communication and the transmission of bioactive compounds to targeted tissues, cells, and organs” including “fibroblasts, neuronal cells, macrophages, and even cancer cells.”

EVs are the postal letters that cells send one another. They come in a variety of sizes from 30 to 1000 nm and have exterior membranes studded with multiple adhesive proteins that grant them entry into any number of different types of cells. Exploiting the biological equivalent to a janitor’s key ring, researchers have begun tucking therapeutic nanoparticles into EVs and using them to discreetly inject treatments into the targeted cells. However, these treatments are still in the experimental stages and are most effective against acute liver failure and inborn metabolic diseases rather than end-stage liver failure.

Mayo Clinic

Mechanical aids, the hepatocytic equivalent to a dialysis machine, like the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL, above) are ideal for treating cases of acute liver failure, able to take over the entirety of the patient’s liver function externally and immediately. However, such procedures are both expensive and temporary. The SRBAL can only support a patient for up to two weeks, making it more suitable for keeping someone alive until a donor can be located rather than as a permanent, pacemaker-like solution.

The bioprinting and implantation of replacement livers has also shown promise, though they too are still in early development and largely not near ready for widespread adoption. Interspecies transplantation using genetically-engineered pig organs are a bit closer to clinical use, with surgeons successfully transplanting a porcine heart into a human patient for the first time this past January (though he died of complications two months later). Pig kidneys and livers have similarly been transplanted into human recipients, often with less drastic side effects than death.

No matter where the transplanted organ comes from, getting it into the patient is invariably going to involve a significant surgical procedure. However, the Lygenesis company recently unveiled its non-invasive solution: tricking the patient’s body into growing a series of miniature, ectopic liver “organoids” in its own lymphatic system like a crop of blood-scrubbing potatoes.

For those of you who dozed through high school bio, a quick recap of terms. The lymphatic system is a part of the immune system that serves to circulate some 20 liters of lymph throughout your body, absorb excess interstitial fluids back into the bloodstream, and incubate critical lymphocytes like T-cells. Organoids, on the other hand, are biological masses artificially grown from stem cells that perform the same functions as natural organs, but do so ectopically, in that they function in a different part of the body as a regular liver. Blood-scrubbing potatoes are self-explanatory.

“Fundamentally, Lygenesis uses the lymph node, your body's natural bio reactors typically used for T-cells,” company CEO and co-founder Michael Hufford, told Engadget. “We hijacked that same biology, we engraft our therapies into the lymph nodes to grow functioning ectopic organs.”

“We use an outpatient endoscopic ultrasound procedure where we're going down through the mouth of the patient using standard endoscopic equipment,” Hufford continued. “We engraft ourselves there in minutes under light sedation, so it's very low medical risk and also is really quite inexpensive.” He notes that the average cost for a proper, in-hospital liver transplant will set you back around a million dollars. Lygenesis’ outpatient procedure “is billed at a couple of thousand or so,” he said.

More importantly, the Lygenesis technique doesn’t require a full donated liver, or even a large fraction of one. In fact, each donated organ can be split among several dozen recipients. “Using our technology a single donated liver can reach 75 or more patients,” Hofford said. The process of converting a single donated liver into all those engraftable samples takes a team of three technicians more than six hours and 70 steps to complete. The process does not involve any gene manipulation, such as CRISPR editing.

This process is quite necessary as patients cannot donate culturable liver cells to themselves. “Once you have end-stage liver disease, you typically have a very fibrotic liver,” Hofford noted. “It will bleed at the slightest sort of intervention.” Even the simple act of collecting cellular samples can quickly turn deadly if the wrong bit of organ is bisected.

And it’s not only the transplant recipients themselves who are unable to donate. Hofford estimates between 30 and 40 percent of donated livers are too worn to be successfully transplanted. “One of the benefits of our technology is we're using organs that have been donated but will otherwise be discarded,” he said.

Once engrafted into a lymph node, the liver organoid will grow and vascularize over the course of two to three months, until it is large enough to begin supporting the existing liver. Hufford points out that even with end-stage disease, a liver can retain up to 30 percent of its original functionality, so these organoids are designed to augment and support the existing organ rather than replace it outright.

Lygenesis is currently in Phase 2A of the FDA approval process, meaning that a small group of four patients have each received a single engraftment in a lymph node located in their central body cavity near the liver itself (the body has more than 500 lymph nodes and apparently this treatment can technically target any of them). Should this initial test prove successful subsequent study groups will receive increasing numbers of engraftment, up to a half dozen, to help the company and federal regulators figure out the optimal number of organoids to treat the disease.

While the liver’s inherent regenerative capabilities make it an ideal candidate for this procedure, the company is also developing similar treatments for the kidneys, pancreas and thymus gland as well as inborn metabolic liver ailments like maple syrup urine disease. These efforts are all at much earlier points in development than the company’s end stage liver work. “Within the next five years, we would love to see our liver program submitted to the FDA as a new biologic therapy and be commercially available,” Hufford said. “I think that'd be a realistic timeframe.”

Study finds surgery patients wearing VR headsets needed less anesthetic

More evidence is mounting that virtual reality might relieve pain during surgery. MIT Newsreports that Beth Israel Deaconess Medical Center researchers in Boston have published a study indicating that patients wearing VR headsets required less anesthetic during hand surgery. While the average conventional patient needed 750.6 milligrams per hour of the sedative propofol, people looking at relaxing VR content (such as meditation, nature scenes and videos) only required 125.3 milligrams. They also recovered earlier, leaving the post-anesthesia unit after 63 minutes on average versus 75 minutes.

The scientists claim VR distracted the patients from pain that would otherwise command their full attention. However, the researchers also admitted that the headset wearers may have gone into the operating room expecting VR to help, potentially skewing the results.

Beth Israel Deaconess' team is planning trials that could rule out this placebo effect, though. One follow-up trial will also gauge the effect of VR on patients receiving hip and knee surgery. Past experiments, such as at St. Jospeph's Hospital in France, have indicated that the technology can help assuage patients.

The allure for healthcare providers is clear. Patients might suffer less and return home sooner. Hospitals, meanwhile, could make the most of their anesthetic supplies, free recovery beds and reduce wait times. What a provider spends on VR headsets could pay for itself if it allows for more patients and higher-quality treatment.

MIT engineers built a robot for emergency stroke surgeries

Remote robotic-assisted surgery is far from new, with various educational and research institutions developing machines doctors can control from other locations over the years. There hasn't been a lot of movement on that front when it comes to endovascular treatments for stroke patients, which is why a team of MIT engineers has been developing a telerobotic system surgeons can use over the past few years. The team, which has published its paper in Science Robotics, has now presented a robotic arm that doctors can control remotely using a modified joystick to treat stroke patients.

That arm has a magnet attached to its wrist, and surgeons can adjust its orientation to guide a magnetic wire through the patient's arteries and vessels in order to remove blood clots in their brain. Similar to in-person procedures, surgeons will have to rely on live imaging to get to the blood clot, except the machine will allow them to treat patients not physically in the room with them. 

There's a critical window of time after a stroke's onset during which endovascular treatment should be administered to save a patient's life or to preserve their brain function. Problem is, the procedure is quite complex and takes years to master. It involves guiding a thin wire through vessels and arteries without damaging any of them, after all. Neurosurgeons trained in the procedure are usually found in major hospitals, and patients in remote locations that have to be transported to these larger centers might miss that critical time window. With this machine, surgeons can be anywhere and still perform the procedure. Another upside? It minimizes the doctos' exposure to radiation from X-ray imaging.

During their tests, the MIT engineers only had to train a group of neurosurgeons for an hour to use the machine. By the end of that hour, the surgeons were able to successfully use the machine to remove the fake blood clots in a transparent model with life-size vessels replicating the complex arteries of the brain.

MIT professor and team member Xuanhe Zhao said:

"We imagine, instead of transporting a patient from a rural area to a large city, they could go to a local hospital where nurses could set up this system. A neurosurgeon at a major medical center could watch live imaging of the patient and use the robot to operate in that golden hour. That’s our future dream."

You can watch a demo of the machine below: