Donate to Science & Enterprise

S&E on Mastodon

S&E on LinkedIn

S&E on Flipboard

Please share Science & Enterprise

Vaccine Patch Shown Safe, Produces Measles/Rubella Antibodies

High-density micro-array patch applied to the upper arm

High-density micro-array patch applied to the upper arm (Vaxxas)

27 Nov. 2023. A vaccine delivered with a patch device is shown in a clinical trial to generate neutralizing antibodies against measles and rubella similar to conventional injections. Results of the trial, conducted among healthy adult volunteers in Australia and reported on 17 Nov. 2023 in the journal MDPI Vaccines, also show the patch-delivered vaccine is safe and well tolerated.

Measles is a highly contagious viral disease causing skin rash, coughing, and sneezing, but largely controlled in some parts of the world through widespread childhood vaccination. Where vaccinations are not readily available, often in lower-resource regions, measles is still a threat to children, and according to the the Measles and Rubella Partnership, claimed 128,000 lives in 2021. Rubella, sometimes called German measles, is a milder form of the disease, but can lead to birth defects among pregnant women, including children with congenital rubella syndrome, a disease causing multiple birth defects.

Vaxxas, a biotechnology company in Cambridge, Mass. and Brisbane, Australia, is developing a patch-applicator device as an alternative delivery vehicle for vaccines. The Vaxxas device uses high-density microscale needles on a small patch, with the needles about 0.25 millimeters in length that do not cause pain, delivered in a single-use spring-loaded applicator. The company says the needles are coated with the vaccine and penetrate to only the outer skin layers, enough to alert the immune system that carries the vaccine to lymph nodes for invoking a general immune response. And Vaxxas says vaccines on the patch can be stored at ambient temperatures without refrigeration.

Science & Enterprise reported on clinical trials of the Vaxxas patch with a Covid-19 vaccine, showing the vaccine delivered with the device is well-tolerated and generates an immune response similar to conventional injections. The company is also testing the patch with a commercial influenza vaccine, and developing another device to deliver a typhoid vaccine. Results from a separate trial support the feasibility of individuals self-administering vaccines with a micro-needle patch, without the supervision of a clinician.

Comparable antibody production rates as injections

In the new early-stage trial, Vaxxas enrolled 63 healthy adult volunteers in Australia to test the patch device with a vaccine against measles and rubella. Participants were randomly assigned to received a patch with either a high or low dose of the vaccine, a placebo patch, or an approved measles-rubella vaccine given with an injection under the skin. After 28 days, the authors report that compared to the beginning of the trial, low-dose vaccine patches generated neutralizing antibodies against measles and rubella at about the same rate (38%) as the conventional vaccine (36%), and twice the rate of the high-dose patches, 19 to 25 percent. The authors say previous vaccination or exposure to measles and rubella created a higher baseline for comparison.

Other findings show patch vaccine recipients displayed at most mild to moderate adverse effects. And the vaccines in the devices were still considered usable even after transported for three days at 40 degrees C or 104 degrees F.

“Measles and rubella remain significant health concerns in many parts of the world,” says Vaxxas CEO David Hoey in a company statement released through BusinessWire, “and we look forward to moving this product forward to later stage clinical trials.” Among the later stage trials, says the company, is an early- and mid-stage study in The Gambia in west Africa among children not yet vaccinated for measles or rubella.

Vaxxas is following a similar strategy for its vaccine patch device as Micron Biomedical Inc., developer of a peel-and-stick patch for vaccines. Science & Enterprise reported in May 2023 on that company’s clinical trial in The Gambia showing its patch vaccine for measles and rubella generated comparable immune responses as conventional injections.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Infographic: A.I. Getting Hype, But Fewer Venture Funds

Bar chart: Venture funding in artificial intelligence by quarter, 2019 to 2023

Click on image for full-size view (CB Insights)

25 Nov. 2023. With all the headlines generated by artificial intelligence these days, one would expect investors would show as much enthusiasm for the technology. According to CB Insights, however, venture investments in A.I. are declining each quarter in 2023, with the number of venture deals reaching a low level not seen since 2017.

In its report issued earlier this month (registration required), technology intelligence company CB Insights says venture investments in A.I. worldwide declined to $8.3 billion in the third quarter of 2023, down from $9.4 billion in the second quarter and $$15.2 billion in Q1. In addition, the number of venture investment transactions in A.I. in the third quarter fell to 501, which CB Insights says is the fewest number of deals for a three-month period since 2017.

In an historical context, the CB Insights report looks less discouraging. The $8.3 billion raised by A.I. start-ups in Q3 2023 is comparable to quarterly investment totals worldwide in pre-pandemic 2019, with the average deal size rising in the third quarter to $26.3 million, from $19.6 million in Q2, and down slightly from $29.3 million in Q1. The median deal size — the half-way mark of smallest to largest transactions — so far this year, however, fell to $4 million by the third quarter, from $4.5 million in 2022 and $5.5 million in 2021.

CB Insights also notes that U.S.-based A.I. start-ups raised $5.8 billion, 70 percent of all venture dollars in the third quarter of 2023, in 236 of the 501 deals. Among the top A.I. investment recipients in Q3 was Generate:Biomedicines in Somerville, Mass. that raised $273 million in its third venture round during September. Earlier this month, Science & Enterprise reported on a demonstration of that company’s generative A.I. technology applied to design of therapeutic proteins, published in the journal Nature.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Academic, Industry Labs to Build Brain Cell Models

Neurons illustration

Neurons (Laura Struzyna, University of Pennsylvania, NIH.gov)

24 Nov. 2023. Researchers from university labs in the U.K. are developing models of brain cell interactions using a company’s synthetic human cells derived from stem cells. The initiative brings together neuroscientists and cell biologists from the biotechnology company bit.bio — the name is spelled in all lower-case — in Cambridge, U.K. and the Institute of Psychiatry, Psychology and Neuroscience or IoPPN at Kings College London.

bit.bio is a six year-old business developing synthetic human cells for research and drug discovery, spun-off from labs at University of Cambridge. The company says its technology called opti-ox, short for optimized inducible overexpression, enables the design of human cells with specific properties and characteristics. The opti-ox process, says bit.bio, is similar to software programming, where the code in this case, is the cell’s genetics. The company says it alters the genome of induced pluripotent stem cells, so-called adult stem cells, with transcription factor proteins that regulate instructions delivered to cells with messenger RNA.

According to bit.bio, this process can be applied to a wide range of human cells, with its main product line called ioCells. One of the company’s applications is a line of synthetic cells for research derived from healthy human donors called ioWild Type Cells. Among the synthetic cells bit.bio offers in this line are neurons or signaling cells in the brain with genes expressing glutamate proteins regulating memory, cognition, and mood, and neurons with genes expressing gamma aminobutyric acid or GABA proteins that limit brain signals, associated with anxiety, stress, and fear. A third ioWild Type Cell are microglia cells that perform repair and maintenance functions in the brain.

Multi-cell models to reveal complex brain processes

Two neuroscientists at IoPPN plan to generate models of interactions among brain cells with ioCells. Deepak Srivastava is a molecular biologist and Anthony Vernon is a pharmacologist, both studying functions of neurons and microglia, including those derived from human pluripotent stem cells. The team expects to build models of brain cell interactions for revealing complex processes in the brain that cannot be demonstrated with single-cell models. For example, says bit.bio, impairment of one cell type may affect the functioning of other cells in the brain.

The company says Srivastava and Vernon already worked with its synthetic cells and are familiar with their properties. “It’s the unique properties of bit.bio’s ioCells,” notes Srivastava in a bit.bio statement, “that will enable us to create a consistent and scalable multi-cell model.” Srivastava adds, “These properties significantly reduce potential concerns that variability in experimental data could be due to variation in the cells in our models.”

Vernon cites schizophrenia as an example where complex brain cell models can better understand how treatments for the disease work. “Whilst antipsychotic medications can be effective,” says Vernon, “they do not address all symptoms of schizophrenia and a significant proportion of individuals show no therapeutic response to these agents. Moreover, they are associated with significant side effects.”

bit.bio says it expects the collaboration with King’s College to run for three years, with the resulting models released to the larger academic community.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Lab-Grown Tissue Company Gains $38M in Seed Funds

Andrei Georgescu and Dan Huh in the lab

Andrei Georgescu, left, and Dan Huh in the lab at University of Pennsylvania in 2019. (Kevin Monko, Penn Today)

22 Nov. 2023. A company producing tissue samples in the lab, for drug discovery and preclinical research with robotics and artificial intelligence, raised $38 million in seed funding. Vivodyne, a three year-old biotechnology enterprise in Philadelphia, is based on research at University of Pennsylvania and Harvard University’s Wyss Institute.

Vivodyne aims to accelerate drug discovery and preclinical testing by creating life-like human tissues for assessing new treatments before clinical trials. Results of this testing, says the company, can also simulate and help design subsequent clinical trials. Vivodyne says its process creates human tissue, including blood vessels, as three-dimensional working samples called organoids on microfluidic chips that simulate organ functions. Organoids are cultured and produced from stem cells, then tested under varying conditions. The company says its organoid models now include bone marrow, small and large airways, liver, solid tumors, pancreas, intestine, placental barrier, uterus for placental implantation, skeletal muscle, and blood-brain barrier.

By using robotics, says Vivodyne, it can simultaneously test an experimental drug with human tissue organoids under various doses and multiple conditions on large numbers of samples. Data from responses of cells and tissue are captured in real time, including images. The company says it uses predictive machine learning models to generate likely responses of single cells and tissue to drug interventions, as well as effects on gene expression, transcription, and protein synthesis. These predictive models, says Vivodyne, can extend the analysis further to the context of known drug interactions, to simulate safety and efficacy outcomes in clinical trials.

“Improve the success rates of A.I.-generated drugs”

Vivodyne was begun in 2020 by biomedical engineering professor Dan Dongeun Huh at University of Pennsylvania and Andrei Georgescu who received his doctorate in Huh’s lab at UPenn. Georgescu and Huh are now the company’s CEO and chief scientist respectively. Huh joined the UPenn faculty in 2013, following work at Harvard’s Wyss Institute for Biologically Inspired Engineering, where he served in that group’s pioneering work with organs on chips. Science & Enterprise reported on a panel led by Huh discussing organ-chips at a scientific meeting in Feb. 2018.

“By combining the principles of organoids and organs-on-chips, we’ve created a new class of life-like, lab-grown human organs,” says Georgescu in a company statement released through Business Wire. Georgescu adds, “The result is huge amounts of complex human data, larger than you could get from any clinical trial, and we train multimodal models on this data to predict and improve the safety and efficacy of new drugs. This breakthrough not only enhances the predictive accuracy of A.I. in drug development, but also promises to significantly improve the success rates of A.I.-generated drugs, setting a new standard in the field.”

Vivodyne is raising $38 million in seed funds, led by technology start-up investor Khosla Ventures in Menlo Park, California. Taking part in the seed round are Kairos Ventures, CS Ventures, MBX Capital, and Bison Ventures. According to Crunchbase, Vivodyne raised $2 million in pre-seed financing in Mar. 2021 from Kairos Ventures. “Vivodyne’s technology,” says Khosla Ventures partner Alex Morgan, “bridges the gap between preclinical R&D and human clinical trials, while automating every step of the testing pipeline, from growing tissues, dosing, sampling and imaging, to analyzing data.”

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Challenge Seeks Precise Addiction Strategies, Biomarkers, Treatments

Heroin abuse illustration

(RenoBarenger, Pixabay. https://pixabay.com/photos/drugs-addict-addiction-problem-2793133/)

21 Nov. 2023. A challenge competition with a $50 million purse seeks new strategies to attack the global substance abuse epidemic, including personalized diagnostics and treatments. Wellcome Leap, an organization in Los Angeles that conducts crowdsourced competitions to rapidly advance the science of health care worldwide is sponsoring the challenge, with an initial deadline for abstracts of 21 Dec. 2023.

The Untangling Addiction challenge, says Wellcome Leap, aims to break a continuing cycle of addiction to alcohol and drugs, leading to early deaths and despair, and affecting every part of the world. The organization cites data showing the number of people worldwide with substance abuse rose by 45 percent between 2009 and 2019. In the U.S., 29.5 million people age 12 and over met the criteria for alcohol addiction, while 24 million are abusing drugs. But all regions, says the group, are struggling with high numbers of people with alcohol and drug addictions.

Compounding the problem, says Wellcome Leap, few current strategies for preventing and treating addictions seem to be working. Only a fraction of the population needing help is receiving treatment, and most addiction treatments follow the same basic approach for each recipient, without considering individual biological or neurological factors. And few effective programs prevent relapses that occur within 90 days among more than half of those treated. In addition, says the organization, new sources of addiction have emerged from abuse of prescription opioid pain killers, serving as gateway drugs for heroin and dangerous synthetic opioids like fentanyl.

Seeking new personalized treatments for addiction

The Wellcome Leap challenge calls for better methods to measure and quantify an individual’s susceptibility for addiction to different substances, particularly opioids, as well as risks of relapse. And the competition seeks new personalized treatments for addiction that allow for quantitative assessments, to reduce relapse and boost abstinence rates.  The organization divides the program into five major topics:

  1. Quantitative addiction measures and models based on biomarkers and neurological indicators
  2. Demonstration and validation of neurological biomarkers for alcohol and drug abuse, particularly those accessible by simple and non-invasive means
  3. Long-term studies of opioid addiction risk, abuse, and prevention strategies
  4. Retrospective studies of biological and health datasets to reveal biomarkers associated with alcohol and drug abuse
  5. New treatments for alcohol and drug abuse, including medications and devices, as well as therapies targeting relapse, with the goal of doubling current efficacy rates

Wellcome Leap is seeking proposals that address one or more of the five topics from individuals, small teams, or coalitions worldwide. The challenge is open to researchers affiliated with universities, research institutes, companies, not-for-profit organizations, and government labs. Initial seven-page abstracts are due by 21 Dec. 2023, with feedback as well as invitation to submit a full proposal returned by 5 Jan. 2024. If invited, full proposals are due by 5 Feb. 2024, with selections for funding made by 6 Mar. 2024.

The Untangling Addiction challenge has a total prize purse of $50 million. However, Wellcome Leap says there are no pre-set award numbers or amounts, with funding determined by the specific proposals. Individuals or organizations not yet registered with Wellcome Leap will need to complete the group’s master funding agreement to receive an award.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

A.I. Analytics Show Blood Test Detects Heart Disease

Heart and major blood vessels

(NIH.gov)

20 Nov. 2023. Data from three health repositories show a simple blood test reveals inherited and acquired genetic indicators, analyzed with artificial intelligence, to detect coronary heart disease. A team from the biotechnology company Cardio Diagnostics Holdings Inc. in Chicago describe their findings from population health data sets and technology in today’s issue of the Journal of the American Heart Association.

Cardio Diagnostics is a six year-old company that seeks to provide simpler and more accessible diagnostics for coronary heart disease, the most common form of heart disease, responsible for more than 375,000 deaths in the U.S. in 2021. Coronary heart disease results from a build up of cholesterol plaques in the large arteries supplying blood to the heart, which can narrow and then block blood flow to the heart. The disorder, also called coronary artery disease, is a major risk factor for heart attacks and heart failure.

The authors note, however, that most of today’s diagnostic tools for coronary heart disease are invasive, expensive, or not sensitive. Exercise stress tests with electrocardiograms or ECGs are non-invasive, but can cost more than $1,100, say the authors, yet return a true-positive sensitivity rate of only 58 percent. An angiogram has a sensitivity rate of 97 percent, but requires an invasive catheter, with contrast agency chemicals and X-rays that can be harmful to some patients. In addition, say the authors, an angiogram can cost more than $9,200.

Hydrocarbon chemicals influencing gene functions and expression

The Cardio Diagnostics solution is a simple blood draw tested for coronary heart disease and analyzed for biomarkers, molecular indicators from inherited genetics and epigenetics, chemical changes in DNA since birth, usually from lifestyle or environmental exposures. The paper’s authors note that epigenetics influenced by smoking or diets high in saturated fats often contribute more to heart disease than inherited genetics. The company’s test, called PrecisionCHD, analyzes blood samples with algorithms to identify inherited and epigenetic DNA contributing to coronary heart disease, particularly methylation signatures: addition of hydrocarbon chemicals that influence gene functions and expression.

Cardio Diagnostics trained the PrecisionCHD machine learning algorithms with data from the Framingham Heart Study, a pioneering long-term assessment of cardiovascular health among residents of Framingham, Mass. across multiple generations. The authors say the algorithms are based on data from 1,545 subjects in the Framingham study using genetic, methylation, and demographic data that accurately detects coronary heart disease in 78 percent of cases, with true-positive sensitivity of 75 percent, and true-negative specificity of 80 percent.

The new paper seeks to validate the PrecisionCHD algorithms by extending the analysis to two independent population health collections — from the Intermountain Health system in Salt Lake City serving Utah and adjoining states, and University of Iowa Hospitals and Clinics in Iowa City — as well as a separate sample from the Framingham Heart Study. Records and blood samples from the three repositories were randomized between those diagnosed with coronary heart disease, and those without the condition, resulting in 449 cases of people with coronary heart disease and 2,067 as the control group. The results show a PrecisionCHD test accuracy of 82 percent, with 79 percent sensitivity, and 76 percent specificity.

Robert Philibert, lead author and chief medical officer of Cardio Diagnostics, calls the findings “a game changer for personalized cardiovascular care” in a company statement, and adds the approach can “provide a more comprehensive, personalized snapshot of a patient’s CHD drivers, allowing for early intervention and tailored treatment plans.” Philbert founded Cardio Diagnostics with Meesha Dogan, a co-author and company CEO, who notes the technology can particularly help patients “in rural areas where advanced diagnostic tools are scarce and cardiovascular specialists are even more rare.” Philibert and Dogan received their doctorates in medicine and biomedical engineering respectively at University of Iowa.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Infographic – China, India Continue as Top Student Sources

World map showing countries with the most international students on U.S. campuses

Click on image for full-size view (Open Doors report, Institute of International Education)

18 Nov. 2023. China and India provided more than half of all international students at U.S. universities in the last academic year, as total enrollment from overseas approached pre-pandemic levels. Institute of International Education in New York this week issued its annual Open Doors report on international students showing more than 1 million students on U.S. campuses in 2022-23.

Some 1.06 million international students enrolled at U.S. colleges and universities in the last academic year, according to the report, an increase of 11.5 percent over the previous year, and just shy of the all-time total of 1.1 million in 2018-19. Of that total, nearly 290,000 came from China with another 269,000 from India, accounting for 27 and 25 percent respectively. Those numbers far eclipsed the 44,000 students from South Korea, and 22,000 to 28,000 each from Canada, Vietnam, and Taiwan. The total number of students from China declined slightly (by 0.2 percent) from 2021-22, but the number of Indian students jumped by 35 percent, the largest increase for any one country.

Some 467,000 students pursued graduate or professional degrees last year, about 44 percent of the total, an increase of 21 percent from the previous year, and the largest number of graduate/professional students ever recorded in the Open Doors data. Undergraduate enrollments from overseas rose at a slower pace (1 percent), but still the first increase in five years. More than half (55%) of international students pursued degrees in science or technology-related disciplines, with nearly a quarter (23 percent) taking computer science and mathematics, and 19 percent enrolled in engineering degrees.

Twelve universities each enrolled 10,000 or more international students in 2022-23, with New York University accounting for 24,500, Northeastern University in Boston taking in nearly 21,000, and Columbia University enrolling 19,000. California and New York universities enrolled more than 125,000 international students in each state last year.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Trial Okayed to Transplant Donated Islet Cells for Type 1 Diabetes

Microscopic image of islet cells from the pancreas

Islet cells from the pancreas (Masur, Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Pancreaticislet.jpg)

17 Nov. 2023. Health authorities in Sweden authorized the start of a clinical trial testing insulin-producing cells from donors engineered to prevent immune reactions in people with type 1 diabetes. Sana Biotechnology Inc. in Seattle says the Swedish Medical Products Agency authorized the trial, a first-in-human study of donated and immune-safe islet cells, held at Uppsala University Hospital.

The trial plans to test an experimental treatment for type 1 diabetes code-named UP421. Type 1 diabetes is an autoimmune variation of the disease where healthy islet cells in the pancreas are attacked as if they were foreign pathogens preventing production of insulin that processes glucose or sugar in the blood. People with type 1 diabetes need to continually monitor their glucose and take insulin regularly to keep blood glucose at safe levels. Centers for Disease Control and Prevention says some 5.7 percent of adults in the U.S. diagnosed with diabetes have type 1.

UP421 aims to provide functioning islet cells from donors to people with type 1 diabetes, without asking recipients to take drugs that suppress the immune system to prevent dangerous immune reactions. Sana Bio says in this trial islet cells from recently deceased individuals, called allogeneic cells, will be engineered with the company’s hypoimmune technology. That technology, says Sana Bio, disrupts expression of human leukocyte antigens, key proteins in the immune system that distinguish between a cells and tissue native to a person and those from outside. The company says hypoimmune also over-produces proteins called CD47, found on many cell surfaces, that stop macrophage immune cells from attacking.

Remove immunosuppression from allogeneic cell transplant

Uppsala University cell biologist Per-Ola Carlsson who studies clinical solutions to type 1 diabetes is leading the trial. “We have performed approximately 165 allogeneic, primary islet cell transplants,” says Carlsson in a Sana Biotechnology statement, “and have seen the benefits for patients, but the complications of immunosuppression inhibit broader use of this procedure. Combining Sana’s hypoimmune technology with primary islet cell transplantation therapy can generate important first-in-human data that may be a step to removing immunosuppression from allogeneic cell transplant in the type 1 diabetes setting.” The research team hopes to report proof-of-concept results for UP421 later this year or in 2024.

Sana Bio says its preclinical research indicates hypoimmune technology has the potential for donated cells to evade immune-system recognition, enabling islet cells in this case to graft in the pancreas, survive, and begin producing C-peptides that enable production of insulin. “Sana’s hypoimmune platform,” notes company CEO Steve Harr, “has shown the potential to evade both allogeneic and autoimmune rejection in preclinical models, and we look forward to seeing if these insights translate into patients, providing a path to cell transplantation without immunosuppression.”

The company expects findings from the trial will help guide development of SC451, Sana Biotechnology’s engineered cells for type 1 diabetes. SC451 applies the hypoimmune process to islet cells derived from induced pluripotent or adult stem cells rather than donated cells. The five year-old company is developing engineered donated and stem cell treatments for cancer, autoimmune disorders, and neurological diseases. Sana Bio is spun-off from labs at Harvard University. Science & Enterprise reported on the company’s start-up in Mar. 2019 and initial public offering in Feb. 2021.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Generative A.I. Designs Novel Synthetic Proteins

Human machine interface

(Gerd Altmann, Pixabay. https://pixabay.com/illustrations/digitization-particles-smartphone-7261158/)

16 Nov. 2023. A biotechnology company demonstrated its technology for designing entirely new types of therapeutic proteins based on a generative artificial intelligence model. Generate:Biomedicines in Somerville, Massachusetts describes its Chroma generative A.I. model in yesterday’s issue of the journal Nature, and is making the model available as open source through GitHub.

Generate:Bio is a five year-old company that designs and develops therapeutic proteins from scratch to meet specific chemical and medicinal properties. The company says its Chroma platform is based on an A.I. neural network or machine learning model trained on amino acid sequences, three-dimensional structures, and statistical patterns of proteins in nature. The model next applies diffusion principles for generating new protein sequences and structures, starting with simple data that then adds more complexity with each following step to achieve the desired functions. In addition, says Generate:Bio, the Chroma technology is programmable, in that the model can be steered to design novel protein structures and sequences that meet chemical and therapeutic objectives specified by the user.

The company says its process can design protein molecules from short peptides to more intricate enzymes, antibodies, and gene therapies. Generate:Bio is developing several of its own protein therapeutics for immunology, cancer, and infectious diseases, with a drug addressing SARS-CoV-2, the virus responsible for Covid-19 infections, in an early-stage clinical trial. The company is also collaborating with M.D. Anderson and Roswell Park cancer centers on therapeutic protein discovery and drug maker Amgen on a number of undisclosed disease targets.

Programming protein output with natural language prompts

In the Nature paper, a team led Generate:Bio co-founder and chief technology officer Gevorg Grigoryan analyzed 120,000 novel protein designs generated by the Chroma model, both single-chain and more complex proteins, but not programmed for specific therapeutic functions. The analysis shows the novel protein designs match many of the properties of natural proteins in the Protein Data Bank, a training source of the company’s algorithms. The researchers also demonstrated programmable structure, folding, sizing, and shaping features of Chroma, even creating proteins shaped like Roman alphabet and Arabic number characters. In addition, the team displayed the ability of programming Chroma output with natural language prompts.

The researchers validated the Chroma model by generating 310 novel designs and testing the proteins they produced on features such as solubility, melting temperature, and expression in E. coli bacteria, a commonly used model species in biology. And the team also produced proteins meeting specified chain lengths, from 100 to 950 amino acids. The authors say their tests show Chroma can produce very large and complex protein designs with standard A.I. graphic processing chips in a few minutes.

Grigoryan — also a professor of computer science and biology at Dartmouth College — says in a Generate:Biomedicines statement, “we have demonstrated that fundamentally new molecular concepts can now be generated at will and used to create novel proteins with a diverse set of desired properties.” Plus, the company is making the Chroma model code available as open source on the GitHub web site. “By making the code open source,” adds Grigoryan, “we’re proud to share this breakthrough in generative biology with the world to help advance our shared goals of fundamentally changing the way protein therapies are created.”

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *

 

Cannabinoid Shown Safe, Lowers Agitation in Alzheimer’s Patients

Cannabis plant

Cannabis plant (Michael Fischer, Pexels.com)

15 Nov. 2023. A clinical trial in a small group of participants suggests a cannabinoid drug is safe and well-tolerated, and reduces agitation among patients with Alzheimer’s disease. Initial results of the trial are published today in a news release from the biotechnology company SciSparc Ltd., developer of the experimental drug tested in the trial, and are not yet peer-reviewed.

SciSparc, in Tel Aviv, Israel, develops treatments for central nervous system diseases with cannabinoids, derived from the cannabis sativa plant. Cannabinoids are substances that contain varying amounts of tetrahydrocannabinol or THC, the mind-altering compound in cannabis, as well as cannabidiol and some 100 other chemicals. Research with cannabinoids indicates some of these compounds have beneficial effects with few adverse effects for treating mental health disorders, with the Food and Drug Administration approving cannabinoid drugs for some forms of epilepsy, and nausea and vomiting in cancer patients undergoing chemotherapy.

SCI-110 is SciSparc’s lead product, in clinical trials for tourette syndrome, obstructive sleep apnea, and now agitation from Alzheimer’s disease. Some people with Alzheimer’s disease and other dementias experience behavior changes including increased fidgeting, restlessness, and agitation. The symptoms may result from changes in the environment of patients such as new caregivers, or fear and fatigue from the disease itself. But the agitation can be damaging to the well-being of both the patient and caregivers, with few options other than calming the patient, removing possible triggers from the environment, and a few medications.

Older adults with Alzheimer’s disease experiencing agitation

SCI-110 is a combination of the cannabinoid drug dronabinol made with synthetic THC, approved by FDA to treat nausea and vomiting in chemotherapy recipients, and the endocannabinoid compound palmitoylethanolamide, or PEA. Endocannabinoids are lipid or natural oil compounds that maintain and protect the central nervous system, by producing enzymes for synthesizing and degrading endocannabinoids as well as by engaging cannabinoid receptors. SciSparc produces SCI-110 as an oral drug.

The clinical trial is a mid-stage study testing SCI-110 among up to 20 patients in an Alzheimer’s care center in Tel Aviv. Taking part in the trial are older adults, age 60 to 85, experiencing agitation but not responding to their current medications. Participants are given SCI-110 twice a day for 64 days with the dose of dronabinol in the drug increased every three days up to 12.5 milligrams. There is no control or comparison group.

The study team is looking mainly for safety indicators in reports of adverse effects and the number of dropouts from the study. But the researchers are also tracking behavioral indicators including a standard agitation assessment inventory, a sleep disorders index, a feeding and eating evaluation scale for dementia patients, measures of impairment, and use of rescue medications.

SciSparc says results from 18 participants show the trial achieved its primary objectives of safety and tolerability, but does not give quantitative data on adverse effects or study drop outs. The company did report a 23 percent decline in agitation symptoms among participants, according to scores on the standard Cohen Mansfield Agitation Inventory. And the scores on the Edinburgh Feeding Evaluation in Dementia Scale, says SciSparc, show fewer eating difficulties. No other behavioral results are reported.

More from Science & Enterprise:

We designed Science & Enterprise for busy readers including investors, researchers, entrepreneurs, and students. Except for a narrow cookies and privacy strip for first-time visitors, we have no pop-ups blocking the entire page, nor distracting animated GIF graphics. If you want to subscribe for daily email alerts, you can do that here, or find the link in the upper left-hand corner of the desktop page. The site is free, with no paywall. But, of course, donations are gratefully accepted.

*     *     *