#Drug Development

[cbirt]

A team of researchers from the University of Chinese Academy of Sciences, China, and collaborators developed GeneCompass, one of the first foundation models of its kind that encompasses a vast expanse of knowledge across a diverse array of species, owing to the fact that it has been trained on over 120 million single-cell transcriptomes derived from the genomes of mice and humans. It is a self-supervised model. During the process of pre-training the model, it retrieves information from four types of biological datasets in the form of ‘prior knowledge’ and integrates it. It has excelled and outperformed several state-of-the-art models when studying a single species. It can also open new avenues for carrying out studies across different combinations of species other than humans and mice. This model can potentially contribute to discovering key regulators that determine cell fate and to identifying promising target candidates in the drug discovery and development field.

It is essential to decode universal regulatory mechanisms that dictate the expression of genes across a diverse set of organisms for accelerating clinical research and expanding our existing knowledge of basic and crucial life processes. Traditional research methodologies and existing deep-learning models have only considered using individual models of organisms separately. This has resulted in a dearth of integrated knowledge of features observed across different cell types over a variety of species. The development of this model was made possible by combining the outcomes of recent advancements in the fields of deep-learning (DL) methods and single-cell sequencing methods.

Continue Reading

#bioinformatics #transcriptomics #gene regulation #artificial intelligence #drug development

[jcmarchi]

Unlocking mRNA’s cancer-fighting potential

New Post has been published on https://thedigitalinsider.com/unlocking-mrnas-cancer-fighting-potential/

Unlocking mRNA’s cancer-fighting potential

What if training your immune system to attack cancer cells was as easy as training it to fight Covid-19? Many people believe the technology behind some Covid-19 vaccines, messenger RNA, holds great promise for stimulating immune responses to cancer.

But using messenger RNA, or mRNA, to get the immune system to mount a prolonged and aggressive attack on cancer cells — while leaving healthy cells alone — has been a major challenge.

The MIT spinout Strand Therapeutics is attempting to solve that problem with an advanced class of mRNA molecules that are designed to sense what type of cells they encounter in the body and to express therapeutic proteins only once they have entered diseased cells.

“It’s about finding ways to deal with the signal-to-noise ratio, the signal being expression in the target tissue and the noise being expression in the nontarget tissue,” Strand CEO Jacob Becraft PhD ’19 explains. “Our technology amplifies the signal to express more proteins for longer while at the same time effectively eliminating the mRNA’s off-target expression.”

Strand is set to begin its first clinical trial in April, which is testing a proprietary, self-replicating mRNA molecule’s ability to express immune signals directly from a tumor, eliciting the immune system to attack and kill the tumor cells directly. It’s also being tested as a possible improvement for existing treatments to a number of solid tumors.

As they work to commercialize its early innovations, Strand’s team is continuing to add capabilities to what it calls its “programmable medicines,” improving mRNA molecules’ ability to sense their environment and generate potent, targeted responses where they’re needed most.

“Self-replicating mRNA was the first thing that we pioneered when we were at MIT and in the first couple years at Strand,” Becraft says. “Now we’ve also moved into approaches like circular mRNAs, which allow each molecule of mRNA to express more of a protein for longer, potentially for weeks at a time. And the bigger our cell-type specific datasets become, the better we are at differentiating cell types, which makes these molecules so targeted we can have a higher level of safety at higher doses and create stronger treatments.”

Making mRNA smarter

Becraft got his first taste of MIT as an undergraduate at the University of Illinois when he secured a summer internship in the lab of MIT Institute Professor Bob Langer.

“That’s where I learned how lab research could be translated into spinout companies,” Becraft recalls.

The experience left enough of an impression on Becraft that he returned to MIT the next fall to earn his PhD, where he worked in the Synthetic Biology Center under professor of bioengineering and electrical engineering and computer science Ron Weiss. During that time, he collaborated with postdoc Tasuku Kitada to create genetic “switches” that could control protein expression in cells.

Becraft and Kitada realized their research could be the foundation of a company around 2017 and started spending time in the Martin Trust Center for MIT Entrepreneurship. They also received support from MIT Sandbox and eventually worked with the Technology Licensing Office to establish Strand’s early intellectual property.

“We started by asking, where is the highest unmet need that also allows us to prove out the thesis of this technology? And where will this approach have therapeutic relevance that is a quantum leap forward from what anyone else is doing?” Becraft says. “The first place we looked was oncology.”

People have been working on cancer immunotherapy, which turns a patient’s immune system against cancer cells, for decades. Scientists in the field have developed drugs that produce some remarkable results in patients with aggressive, late-stage cancers. But most next-generation cancer immunotherapies are based on recombinant (lab-made) proteins that are difficult to deliver to specific targets in the body and don’t remain active for long enough to consistently create a durable response.

More recently, companies like Moderna, whose founders also include MIT alumni, have pioneered the use of mRNAs to create proteins in cells. But to date, those mRNA molecules have not been able to change behavior based on the type of cells they enter, and don’t last for very long in the body.

“If you’re trying to engage the immune system with a tumor cell, the mRNA needs to be expressing from the tumor cell itself, and it needs to be expressing over a long period of time,” Becraft says. “Those challenges are hard to overcome with the first generation of mRNA technologies.”

Strand has developed what it calls the world’s first mRNA programming language that allows the company to specify the tissues its mRNAs express proteins in.

“We built a database that says, ‘Here are all of the different cells that the mRNA could be delivered to, and here are all of their microRNA signatures,’ and then we use computational tools and machine learning to differentiate the cells,” Becraft explains. “For instance, I need to make sure that the messenger RNA turns off when it’s in the liver cell, and I need to make sure that it turns on when it’s in a tumor cell or a T-cell.”

Strand also uses techniques like mRNA self-replication to create more durable protein expression and immune responses.

“The first versions of mRNA therapeutics, like the Covid-19 vaccines, just recapitulate how our body’s natural mRNAs work,” Becraft explains. “Natural mRNAs last for a few days, maybe less, and they express a single protein. They have no context-dependent actions. That means wherever the mRNA is delivered, it’s only going to express a molecule for a short period of time. That’s perfect for a vaccine, but it’s much more limiting when you want to create a protein that’s actually engaging in a biological process, like activating an immune response against a tumor that could take many days or weeks.”

Technology with broad potential

Strand’s first clinical trial is targeting solid tumors like melanoma and triple-negative breast cancer. The company is also actively developing mRNA therapies that could be used to treat blood cancers.

“We’ll be expanding into new areas as we continue to de-risk the translation of the science and create new technologies,” Becraft says.

Strand plans to partner with large pharmaceutical companies as well as investors to continue developing drugs. Further down the line, the founders believe future versions of its mRNA therapies could be used to treat a broad range of diseases.

“Our thesis is: amplified expression in specific, programmed target cells for long periods of time,” Becraft says. “That approach can be utilized for [immunotherapies like] CAR T-cell therapy, both in oncology and autoimmune conditions. There are also many diseases that require cell-type specific delivery and expression of proteins in treatment, everything from kidney disease to types of liver disease. We can envision our technology being used for all of that.”

#Alumni/ae #approach #Behavior #bioengineering #Bioengineering and biotechnology #Biological engineering #Biology #blood #breast cancer #Cancer #cancer cells #cell #cell therapy #cell types #Cells #CEO #challenge #change #Companies #computer #Computer Science #covid #Database #datasets #deal #Disease #Diseases #drug development #drugs #easy

[bpod-bpod]

Cancer-crushing Corals

From fluorescent jellyfish proteins to drug-inspiring cone snail toxins, marine animals are a biomedical treasure trove. Soft corals and their relatives, collectively known as octocorals, possess a vast library of particularly promising compounds, diterpenes, currently under investigation as potential drugs. Yet, with little understanding of how they are produced, synthesising them in the laboratory has proved difficult, hindering progress. In a recent breakthrough, researchers identified a cluster of genes involved in the synthesis of eleutherobin, a coral diterpene with potent anti-cancer activity, in the genome of the soft coral Erythropodium caribaeorum (pictured). Unlike in many marine animals, eleutherobin is not produced by a bacterial symbiont, a microbial partner living within the coral, but by the coral itself, and similar genes exist in other octocoral genomes, suggesting that diterpene production is an ancient adaptation. Elucidating this genetic pathway provides key tools for making coral diterpenes, boosting their potential for drug development.

Written by Emmanuelle Briolet

Image by Naturalis Biodiversity Center

Research by Paul D. Scesa, Zhenjian Lin & Eric W. Schmidt, Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA

Image originally published with a Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0) license

Research published in Nature Chemical Biology, May 2022

You can also follow BPoD on Instagram, Twitter and Facebook

#science #biomedicine #cancer #cancer drugs #oncology #tumours #drug development #coral #diterpenes #soft coral #marine life #anti-cancer drugs

[sanguinifex]

This is huge. As of 8/30/2023, the Federal Department of Health and Human Services wants the DEA to reclassify from schedule 1 (no medical use, completely verboten) to schedule 3 (widely accepted medical use, some abuse potential, similar to Tylenol 3).

It won’t just allow doctors to prescribe it and reduce the penalties for having it if you’re not “supposed to”; it’ll also make it much easier for researchers to do studies with it, giving us health data that is currently lacking. For example, we don’t know much about how THC and CBD affect the liver or liver enzyme levels except in end stage liver disease patients, and what data we do have is decades old and of poor to middling quality.

The expansion of research a Schedule 3 reclassification would allow could pave the way for a safe, non-addictive pain medication based on cannabinoids that works primarily on the CB2 receptors and either doesn’t pass the blood-brain barrier or does cross it but doesn’t cause euphoria or sedation in most patients. In other words, the holy grail of pain medicine. Currently, the only painkiller that utilizes the endocannabinoid system is acetaminophen (Tylenol), which is a weak reuptake inhibitor of anandamide but primarily works via the prostaglandin system, and which is also highly hepatotoxic and somewhat nephrotoxic, and which probably wouldn’t be approved except as prescription fever and pain management, the latter primarily as an adjuvant to opiates, if it were a new drug being reviewed by the FDA today.

This is a really big example of how both parties are not the same. A Republican administration DHHS wouldn’t do this. If the No Fun Allowed Agency follows instructions, this opens up a lot of possibilities for a lot of people. It also completely bypasses the partisan legislatures and courts. Technically it’s easier for a future administration to overturn, but historically the DEA rarely reschedules medications without strong external pressure. (And in this case, it’s already functionally legal for those 21+ in most of the country anyway.)

#cannablr #cannabis legalization #drug development #drug research #us politics

[intrinsequehealth]

Intrinseque Health - Clinical Supply Chain We Build and Execute Complex Clinical Supply Plans

Intrinseque Health is an EN ISO 13485 Certified Global clinical trial support services provider committed to the utmost in service delivery to drug development organizations (Pharmaceutical, Biotechnology, Medical Device & Contract Research Organizations (CROs)). Our team of industry professionals has over 300 years of combined experience supporting global clinical trials across a wide array of therapeutic areas. This vast experience enables us to empathize with our Customers while providing best-in-class solutions to overcome the hurdles and pain-points of conducting a clinical trial.

Regions & countries throughout the world will often present a unique set of regulatory and logistical challenges. It is our responsibility to understand and overcome these while ensuring that your products, supplies, equipment and services are available where needed to ensure study timelines are met. Intrinseque Health utilizes an operational methodology that is based on proven, cost-effective clinical supply chain strategy for each clinical trial. Our practice is to engage with our customers, early and often to ensure implementation of a robust clinical supply plan, resulting in the most successful study start-up and initiation.

#clinical supply #clinical trials #health #healthcare #supplychainmanagement #clinical supply chain #clinical supply chain management #drug development

[chariotdagawd]

The Relevance of Vitamins and also Minerals for a Healthy And Balanced Body

Nutrients are essential nutrients that the body needs to function appropriately. They are accountable for a variety of procedures, including structure solid bones, supporting the body immune system, and also converting food into power. While a healthy diet plan should give most of the necessary minerals and vitamins, many individuals do not consume enough of these nutrients. This can cause shortages and illness.

To make certain that you are getting sufficient vitamins and also minerals, it is necessary to eat a variety of foods from all food groups. Fruits, veggies, entire grains, lean proteins, as well as dairy products are all great resources of vitamins and minerals. If you are unable to get enough nutrients from your diet alone, supplements may be needed. Nonetheless, it is very important to chat to your physician before taking any supplements, as some can connect with drugs or cause harm if absorbed unwanted. By making sure you are getting enough nutrients, you can assist maintain a healthy body and also protect against deficiencies that can cause severe health and wellness issues.

Read more here over-the-counter medicines

#drug development

[sbgridconsortium]

Ligand and G-protein selectivity in the κ-opioid receptor

The dark history of opioids use in pain management is a testament to the complexity that comes with discovering potential drug targets in the brain. The therapeutic target of opioids is usually the μ-opioid receptor (MOR). This interaction between the MOR and opioids creates the sensation of pain relief by the downstream signaling of the MOR through the Gi/o-family proteins. Sadly, MOR has downstream effects that can cause outcomes other than diminishing pain, like addiction and abuse. 

For this reason, other viable targets for pain management are important in trying to lessen dependence on opioids. One way to lessen the unintended consequences of opioids while still effectively managing pain is to target pathways relevant to pain relief downstream of the MOR while avoiding pathways that cause other effects. One possible target could be the κ-opioid receptor (KOR). This receptor targets similar downstream effects responsible for the pain reducing effects of the MOR, while not causing the similar levels of addiction. The KOR does however, tend to cause hallucinogenic symptoms when targeted. 

Above: Published structure of KOR bound to Gg protein. PDB: 8DZR. CC BY SBGRID

To provide insight on this effect, SBGrid member Tao Che and collaborators studied how ligand binding to KOR affects its signaling machinery, the Gi/o-family proteins. Using cryo-EM, they studied the specificity of the KOR to ligands and the selectivity of four types of Gi/o-family proteins to the KOR/ligand complexes. From these structures the authors are able to determine a high level of selectivity of KOR to specific ligands and high levels of selectivity of G proteins to KOR/ligand complexes. The specificity of certain Gi/o-family proteins to certain KOR/ligand complexes could suggest that therapeutics can be designed to not only target the KOR, but also select desired downstream pathways by signaling through specific Gi/o-family proteins.

Read more about this work in Nature.

-Vida Storm Robertson, Fisk University

#structural biology #cryo em #neuroscience #drug development #ligands #sbgrid member research

[abybweisse]

hiya! loooove ur acc, I find myself regularly going on several hours long reading sessions into all ur old posts XD

I just wanted to ask about when you said this:

do you think this could have anything to do with why the r!ciel and the other dolls need to "drink" blood? and why they seem saner/actually conscious compared to the ones on the campania?

like maybe there's trace amounts of a humans soul in their blood? and so since the campania dolls didn't get blood transfusions (I'm assuming) from UT, they went out trying to gain what they don't have.

but if there are parts of souls in human blood, then that mindless need to find a soul can be subsided bc the more advanced dolls actually HAVE bits of souls in them? but it runs out eventually which is why they need to keep having more transfusions from living people. (maybe the blood isn't going bad or anything, there's just no soul left in it)

my personal idea/hc for the kuro universe is that a soul is like a kind of energy source for consciousness, and the cinematic record is powered by it. UT can edit the record, but he can't get it up and running again, and making new memories without something to power it.

so a human is like a computer, a soul is like the electricity in it, the brain is the hardware (UT can't bring someone back if the brain is destroyed), and the cinematic record is the software if that makes sense?

love to hear your thoughts! 💖💖

Oooh, thank you, but I hope you are getting enough sleep!

How bizarre dolls work

You make some good points, but there's one thing missing up there: the bizarre dolls that are the link between the mindless ones on the Campania and these highly advanced ones he calls "lords of the stars". Agares, Derrick, and his pals are the first bizarre dolls we meet who are capable of speech. The students weren't particularly good vessels for this technique, since they didn't seem to have many "episodes", but Agares was better. Before he resorts back to the mindless, speechless, biting variety, he knows something is wrong and that he isn't going to hold onto his mind much longer.

They were not receiving blood transfusions, so no injection of "trace amounts" of soul, as you say. And yet they were talking, and Agares could actually think for himself a little bit; Agares might have even been creating new memories to store on his cinematic records. Don't know that I can say the same for Derrick or the others, though.

Anyway, somewhat advanced bizarre dolls (like Agares) can go just fine on "episodes" alone, and Undertaker says real Ciel is "chock full" of such episodes. What's weird is how the most advanced bizarre dolls wear out (and can even collapse) when their blood levels go down or run out of nutrients. The less advanced bizarre dolls moved around without fresh blood... and sometimes big chunks missing. So, what makes these most advanced ones so reliant on the blood? Is it like an addiction?! Layla biting people because her cravings are so strong kind of suggests so.

Truth is, we don't know much about all the different techniques Undertaker is using now, on top of altering cinematic records and transfusing blood. There could be meds/drugs involved, since there was previous talk about a group doing drug development. Didn't Stoker say that's what the Osiris group was, a drug development organization?

So, the soul or "trace amounts" of soul aren't needed to keep the cinematic records going. It isn't even needed to make bizarre dolls talk and create new memories.

I'm not entirely sure blood has "trace amounts of soul" in it, despite what I said in the screenshot you captured. More like: what if the demon sucked up the blood seeping through and that drew the soul out, turned the blood into a conduit for the soul? Does that make any sense?

Idk. Perhaps the blood "naturally" has something in it that makes bizarre dolls feel like they are getting something soul-like out of it. Even Sebastian has been seen licking his own blood (circus arc), and s2's Claude reacts rather oddly to tasting the blood that splashes onto his face. 🤷🏻‍♀️ Whatever that something is, it definitely doesn't last. Perhaps if Undertaker could get their kidneys working again.... Maybe blood and soul interact within the body, and blood collected for transfusion doesn't take away from the donor's soul in any way, so not even trace amounts being removed, but that blood has some residue of another kind or some special quality, simply from having recently been in contact with a living soul. Again 🤷🏻‍♀️. There sure is the phrase, though: "heart and soul".

But the soul definitely has the essence of someone's true personality. They can be conscious without it, but they have no real conscience. Without that essence, their driving force (provided by episodes) is two-dimensional or superficial. They need souls for their full depth of character.

#black butler #kuroshitsuji #bizarre dolls #bizarre doll ciel #agares #derrick arden #campania #weston #blue sect #rian stoker #aurora society #osiris #drug development #soulless #blood #heart and soul #undertaker #advanced bizarre dolls #blood transfusion #peggy-uwu #asks #i answer #answered asks #may 23 2022

[happy-smile-flowers]

Inventory of the three major in vitro pharmacokinetic research methods

The metabolic properties of a compound are an essential factor in whether or not it can be used as a drug in the clinical setting, so pharmacokinetic studies of newly synthesized compounds are required in drug development.

In vitro incubation with liver microsomes, recombinant CYP450 enzyme lines, and in vitro incubation with hepatocytes are some of the more common in vitro drug metabolism methods.

1. In vitro incubation method with liver microsomes

The metabolic stability and metabolic phenotypes of candidate compounds in different species of liver microsomes are good predictors of the metabolic properties of compounds in vivo. They are practical tools for evaluating candidate compounds in the pre-development phase of drug development. Liver microsomes include rat liver microsomes, human liver microsomes, canine liver microsomes, monkey liver microsomes, and mouse liver microsomes.

In in vitro incubation of the liver, microsomes are the "gold standard" for in vitro drug metabolism in drug discovery, drug metabolic characterization, and drug interaction studies of new chemical entities, and is currently the most widely used method for clinical and preclinical pharmacokinetic studies.

Medicilon has rich experience in vitro research on pharmacokinetics, including metabolic stability, P450 induction and inhibition, metabolic pathway, and metabolite identification, with animals involved, including rats, mice, rabbits, dogs, and monkeys.

Microsomes are vesicles formed by endoplasmic reticulum fragments obtained by homogenization through ultracentrifugation, containing all components of CYPs. They are widely used for their simple preparation technique, fast metabolic process, good reproducibility of results, easy operation in large quantities, and long-term stability at -80°C.

According to online reports, researchers at other companies investigated the in vitro metabolism of Chrysanthemum bicolor in human liver microsomes, and the in vitro co-incubation of liver microsomes blank control, ethanolic solution of Chrysanthemum bicolor alcoholic extract, inactivated liver microsomes plus Chrysanthemum bicolor alcoholic extract and liver microsomes plus Chrysanthemum bicolor alcoholic extract was performed by high-performance liquid chromatography[1]. The results showed that the content of each component of the alcoholic extract of Chrysanthemum bicolor was reduced under the action of human liver microsomal drug-metabolizing enzymes, and four substances were metabolized but not detected. The alcoholic extract of Chrysanthemum bicolor could be metabolized and eliminated more rapidly under the action of human liver microsomal drug-metabolizing enzymes.

Two 、Gene recombination CYP450 enzyme system technology

The cytochrome P450 (CYP450) enzyme family has enzyme proteins encoded by gene superfamilies involved in the biotransformation of many endogenous and exogenous substances. The effect of drugs on cytochrome P450 enzyme activity is one of the leading causes of drug interactions. Recombinant enzymes are a reliable method for studying the metabolic characterization of CYPs due to their single composition and explicit drug metabolic characterization, and genetically recombinant P450 enzyme lines are increasingly used in in vitro hepatic metabolism studies of drugs.

Genetically recombinant P450 enzyme lines, i.e., using genetic engineering and cell engineering, the genes regulating the expression of P450 enzyme lines are integrated into E. coli or insect cells are cultured to express high levels of P450 enzyme lines and purified to obtain a purer single P450 isoenzyme. Genetically recombinant P450 enzyme lines for in vitro hepatic metabolism studies of drugs have unique advantages in identifying the enzyme isoforms that induce drug metabolism and studying drug-drug interactions and thus have further penetrated various fields of drug metabolism studies.

3. In vitro incubation method with liver microsomes

In vitro incubation of hepatocytes is similar to the liver microsome method, i.e., a system in which prepared hepatocytes are supplemented with redox coenzymes to carry out metabolic reactions under simulated physiological and environmental conditions. The hepatocytes in the incubation system can reasonably simulate the physiological environment of the liver in vivo and have many advantages in studying the biological activity, toxicity, toxicological mechanism, metabolic fate, and carcinogenicity detection of exogenous compounds and are considered a reliable model for preclinical toxicity testing of drugs. For example, some researchers have established an in vitro warm incubation model of rat primary hepatocytes: After warm incubation of serpentine with rat primary hepatocytes, the serpentine content in the warm incubation solution was determined by applying HPLC method to study its metabolic characteristics in vitro.

 The liver is an essential organ of drug metabolism and is the leading site of biotransformation in the body. It is rich in an extensive system of cytochrome P450-dependent mixed-function oxidative enzymes involved in drug metabolism. Most of phase I and phase II reactions of drugs depend on the hepatic enzyme system for their occurrence. The elucidation of critical enzymes of drug metabolism and their metabolic pathway realization provides a significant reference value for the rationale and safety of clinical drug use.

[1] In vitro metabolism study of Chrysanthemum bicolor in human liver microsomes [J].

#liver microsomes #medicine #health #drug development #chrysanthemum

[kp777]

Andrew Hopkins of Exscientia: the man using AI to cure disease

#artificial intelligence #ai #andrew hopkins #medical research #medical science #drug development

[worldipday]

Africaʼs First Integrated Drug Discovery and Development Platform.

Africaʼs first integrated drug discovery and development center. H3D was founded at UCT in April 2010 and focuses on translational medicine, which involves early-stage medicine discovery in the lab through to the treatment of patients in clinical settings. WIPO Magazine recently sat down with Chibale to learn more about H3D, and the role intellectual property plays in its groundbreaking work.

WM: What is the potential of drug discovery in Africa? KC: Africa is arguably the most genetically diverse continent.

Everybody came from Africa and went somewhere else. That means diseases are not African problems or African diseases, they are human diseases, human problems. So, drug discovery in Africa has huge potential to contribute to humanity and to create local jobs.

And how is H3D affecting health innovation in Africa?

H3D is having an impact at various levels, particularly by creating drug discovery infrastructure and platforms capable of contributing to the global pipeline of innovative products that could be further developed. In other words, we have strengthened our capacity to translate basic science knowledge into potential life-saving medicines. And we are bridging the gap between the lab and the patient.

You focused initially on malaria. Why?

Malaria was an opportunity for us to build the infrastructure required for translational medicine. At the end of the day, beyond understanding the biology of the human malaria parasite, the drug discovery principles are the same for malaria or cancer. For example, regardless of the disease, among other things, the common goal is to understand how the human body will handle the drug candidate. The malaria project was an opportunity to work with the Medicines for Malaria Venture (MMV) and to subsequently engage with new partners, such as Merck and the Bill and Melinda Gates Foundation. Once we developed the infrastructure we needed for that project, we began adding other diseases, including tuberculosis (TB), and antimicrobial resistance. In 2022, we had an opportunity to work with Johnson & Johnson as one of the companyʼs three satellite centers for global health discovery. In sum, malaria was an anchor program that enabled us to acquire the skills and experience we wanted to develop, and which we then transferred to other diseases.

How important are such partnerships to H3Dʼs work, and to developing a robust health innovation ecosystem in Africa?

Partnerships are extremely important, even for innovative pharmaceutical companies with financial muscle. Indeed, some of the product portfolios they offer include drug candidates licensed in from third parties. This enables them to de-risk the early stages of drug development. For H3D, partnerships were important from the start, for three reasons. First, to tackle infrastructure challenges; second, to build the technology platforms we needed; and third, to access skilled people. Partnerships are also important to secure funding. When you have a project with global support, you attract partners who share the same goals, funding grows, and you gain access to a network of centers of excellence. Partnerships can bring to the table what you donʼt have, because everyone is interested in the projectʼs success. When there is mutual interest, you can make a huge difference.

What about the importance of building a local procurement support system? One of the main barriers to scientific innovation in Africa has been a lack of infrastructure in the broad sense. This includes a local procurement support system with functioning laboratories, access to the spare parts you need when something breaks down, the ability to access reagents and chemicals readily and rapidly, and so on. Of course, from a business perspective, we need scale that justifies the business. At present, there are too few players, so business opportunities are limited. Thatʼs why weʼre working to expand the community to create the demand that will foster the businesses we need to supply the chemicals and reagents required for research and development, for example.

What is the role of intellectual property in all this? When thereʼs an unmet medical need, you have to innovate, and IP incentivizes innovation. IP is an enabler and underpins robust innovation ecosystems. Cash-strapped universities can use IP to generate new sources of income from their research, through university spinouts, for example. IP is also a magnet for investment. People want to invest in a country where there is respect for rules and laws, including IP.

Do you still need IP in Africa for infectious diseases, where commercial returns are low? Absolutely. Because IP is also a responsibility, even for infectious diseases where commercial returns are perceived to be low. Without IP you would have a free-for-all. When it comes to health equity, itʼs important to remember that the person who owns the IP can decide whether to share it voluntarily or not.When you hold IP rights in a medicine, you can control its use to some extent. Thatʼs why, in Africa, we need to be owning IP. When we do, and we find an appropriate partner to take the IP forward, we get a return. I would rather own 1% of one billion than 99.99% of zero.

IP is also a responsibility, even for infectious diseases where commercial returns are perceived to be low.

What is the current focus of H3Dʼs work? In terms of drug discovery, weʼre focusing on action studies to identify biological targets and to better understand the mechanism of resistance of these targeted organisms to drugs. These organisms are very clever. Our job is to outsmart them.

Do you still see the need for new approaches? Yes. At a scientific level, Iʼm an advocate for Afro-centric drug discovery. You need to find a target to hit – an enzyme or a protein – which may respond differently in different populations for genetic reasons.

Genetic differences in the expression and activity of drug-metabolizing enzymes can lead to variable responses to therapeutics. For example, in people of African descent, due to genetic mutations, enzymes responsible for metabolizing the antiretroviral drug Efavirenz work more slowly than in other populations and this can result in toxicity, even death, due to drug overdose if dosages arenʼt adjusted appropriately. So, drug development needs to move from a one-size-fits-all focus toward a population-centric approach. We really need to invest in understanding the genetics of the African population with respect to biological drug targets we go after and the enzymes responsible for metabolizing specific drugs. Also, we need to address the funding gap in translational medicine, which many investors find too risky. This will require policy changes to encourage investors to see drug development as a continuum that requires investment at each stage of the value chain. This would create opportunities to share both risks and benefits, and ultimately will benefit everyone.

Read the full interview online and learn more about Chibaleʼs recommendations for developing a robust health innovation system in Africa.

#medicine discovery #intellectual property #health sector #drug discovery #health innovation #26 april #worldipday #pharmaceutical #drug development #sdg3 #ip and the sdgs

[cbirt]

A team of researchers at the University of California, San Diego, came together to develop a chatbot specifically catered to drug discovery called DrugChat. It is similar to ChatGPT on the basis that users can give question prompts to the model on any drug compound under study after uploading the drug’s molecular graph and can get answers to their queries in an interactive and iterative manner. It is composed of a graph neural network (GNN), a large language model (LLM), and an adaptor.

Traditional methods of drug discovery, which have been carried out experimentally, have been expensive and time-consuming. Approval for even a single drug to go up in pharmaceutical stores for sale takes several years and a lot of money. Experimental methods also require a lot of labor and step-by-step testing, often ending up in failure at the last few stages of drug development. Taking advantage of artificial intelligence (AI) to mitigate these issues is crucial in today’s fast-paced and demanding world, where novel drugs are needed to treat an ever-increasing list of diseases.

Continue Reading

#bioinformatics #drug discovery #ai #drugchat #chatgpt #llm #drug development

[scientificinquirer-blog]

Butantan Institute’s dengue vaccine protects 79.6% of those vaccinated, study shows

A single-dose dengue vaccine produced by Butantan Institute in São Paulo state (Brazil) prevents development of the disease in 79.6% of those vaccinated, according to an article published today (February 1) in The New England Journal of Medicine. Called Butantan-DV, the vaccine contains attenuated versions of all four dengue virus serotypes. The results of the ongoing Phase 3 trial show that it…

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#dengue #drug development #South America #vaccines

[aragenlifesciences]

Maximize efficiency with top-tier Small Molecule API solutions

Discover top-tier CDMO pharma companies specializing in small molecule API synthesis and manufacturing. Elevate your drug development journey with Aragen's comprehensive solutions tailored to meet your small molecule needs.

#small molecule api #small molecules #drug development #life science

[sanguinifex]

Naked mole rats don’t just survive via using fructose to bypass oxygen. They also got rid of the kind of pain that doesn’t mean “immediate danger.”

Imagine getting a viral vector gene therapy that turns off fibromyalgia. I, for one, am looking forward to that future.

#naked mole rat #science #biology #genetics #drug development #biologics

[lifeisblootiful]

The Necessary Guide to Vitamins and also Minerals: Unlocking the Power of Nourishment for Optimum Health

Paragraph 1: Minerals and vitamins play a critical duty in maintaining our general wellness as well as health. From improving our immune system to supporting proper mind function, these vital nutrients are the foundation that our bodies need to work at their finest. In this thorough guide, we will certainly dive deep right into the world of nutrients, untangling their benefits, resources, and the significance of preserving a well balanced intake for ideal health.Paragraph 2: Minerals and vitamins are not only essential for our bodily features, however they additionally work as effective antioxidants, shielding our cells from damage brought on by damaging complimentary radicals. While a healthy diet needs to ideally offer us with all the essential nutrients, particular aspects such as inadequate nutritional options, tension, contamination, and also medications can lead to shortages. That's where supplements enters into play. We will discover the different kinds of minerals and vitamins, their particular features, and just how to determine if you require to supplement your diet plan to guarantee you're getting the ideal amount of these crucial nutrients. Whether you're wanting to enhance your power degrees, support your body immune system, or improve your skin health and wellness, understanding the globe of minerals and vitamins is the very first action in the direction of achieving ideal health.

Read more here find your passion

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