Category: New Compounds and Treatments

Categories : Cancer New Compounds and TreatmentsTags :

Novel Glioblastoma Drug Can Cross The Blood-brain Barrier

On By ModernMedia

An experimental spherical nucleic acid (SNA) drug was able to penetrate the blood-brain barrier and trigger glioblastoma tumour cell death in an early clinical trial.

Glioblastoma is the most common and aggressive brain tumour, accounting for 16% of cases. It affects 3.2 per 100 000 people, at an average age of 64 years although it can appear at any time.

The new drug, NU-0129, is the first SNA drug developed for systemic use. The SNA groups RNA or DNA around a nanoparticle. A revolutionary new class of drugs, it can be adapted to a number of neurological diseases such as Parkinson’s.

“We showed the drug, NU-0129, even at very small doses, causes tumour cells to undergo what’s called apoptosis or programmed cell death,” said lead investigator Dr Priya Kumthekar, associate professor of neurology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “It’s a remarkable finding in humans that confirms what we had previously seen in our animal studies.”

The study participants received the drug intravenously prior to surgery to remove the tumour. The researchers team studied the tumours to determine how well the drug crossed the blood-brain barrier and its effect on their cells.

“This unique 3D design has the ability to infiltrate tumor cells to correct the genes inside and make them susceptible for therapy-induced killing,” said senior author Alexander Stegh, an associate professor of neurology at Northwestern.

Unusually, the drug was developed entirely within the university without involving pharmaceutical licensing.
“We want to move the technology forward as quickly as possible because there are patients with a disease with no current cure,” Kumthekar said.

Dr Leon Platanias, director of the Lurie Cancer Center, said, “These exciting findings for the first time support the potential of spherical nucleic acids for drug delivery to brain tumors. They may prove to have important long-term translational implications for the treatment of these tumours.”

Source: Medical Xpress

Journal information: P. Kumthekar el al., “A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma,” Science Translational Medicine (2021). stm.sciencemag.org/lookup/doi/ … scitranslmed.abb3945

Categories : Immune System New Compounds and TreatmentsTags :

New Compound Can Reduce Inflammation Without Dampening Immune Response

On By ModernMedia

Researchers from Nanyang Technological University (NTU), Singapore, have discovered a compound that is capable of dampening immune overactivity without the cost of reducing the immune response.

The new compound, ASO-1, targets tyrosine kinase 2 (TYK2), a member from the Janus kinase (JAK) family of enzymes involved in immune response regulation. These enzymes have received attention in recent years as targets for drugs to treat immune system overactivity, and TYK2 is a possible therapeutic target for cancer treatment. A recent study found that high levels of TYK2 have been associated with severe COVID.

“Human genetic studies have suggested that deactivating TYK2 could provide protection against a broad range of autoimmune conditions such as rheumatoid arthritis, psoriasis, lupus, and type 1 diabetes,” said Phan Anh, Professor and Interim Director, Institute of Structural Biology, NTU.

Co-lead author Dr Lim Kah Wai, NTU senior researcher, added: “With the UK-led study of critically ill COVID patients published in Nature linking high TYK2 expression to severe COVID, ASO-1 could be a therapeutic agent worth investigating further. We are planning to conduct further pre-clinical work to validate its therapeutic potential.”

The ASO-1 compound designed by the researchers is an antisense oligonucleotide (ASO), which targets messenger RNA (mRNA).  ASO-1 was identified from over 200 potentially effective ASOs designed by the team.  ASO-1 is designed to bind to TYK2 mRNA and prevent the cells from making the TYK2 protein. ASO-1 has to be highly selective for TYK in order to prevent side effects involving other JAK enzymes.

Through in vitro testing, the NTU scientists found that ASO-1 greatly reduced TYK2 levels over a sustained period and inhibited immune signalling pathways associated with autoimmune disorders. This points to the potential of the ASO-1 compound forming the basis for treatment of autoimmune conditions, There was also no effect against the other JAK proteins. Dr Lim noted that this high potency of ASO-1 rivals that of recent ASO drug candidates under development.

The team plans academic collaboration for further development of ASO-1 and animal model testing.

Source: News-Medical.Net

Categories : Mental Health New Compounds and TreatmentsTags :

Neurocrine’s Anticipated Schizophrenia Drug Flops in Clinical Trial

On By ModernMedia

Pharmaeceutical company Neurocrine’s anticipated schizophrenia drug, luvadaxistat, failed to have an impact on negative symptoms in a key clinical trial, but still showed promising cognitive benefits.

Neurocrine Biosciences had licensed seven of Takeda’s psychiatry drugs last year for over $2 billion. Luvadaxistat was the furthest along, having entered Phase 2 testing in 2017.

The experimental drug is supposed to help schizophrenia patients cope with “negative symptoms”—a range of difficult-to-treat conditions such as lack of motivation, trouble communicating and limited emotion. The drug is designed to block an enzyme that degrades a certain kind of amino acid important for brain function.

However, according to results from a mid-stage study, in comparison to placebo, patients treated with the drug didn’t perform significantly better, as measured by a scale that assesses the severity of negative symptoms.

While there was excitement around the science behind luvadaxistat, Wall Street analysts lost much of their optimism in the programme last month, after Concert Pharmaceuticals halted development of CTP-692, an experimental drug based on the same mechanism, after trials also saw disappointing results. 

Nevertheless, there remains a path ahead for luvadaxistat as Neurocrine is setting up to analyse the drug’s efficacy for cognitive benefits, as it appears that these results at least were in line with scientific predictions.

Source: BioPharma Dive

Categories : New Compounds and TreatmentsTags :

A Natural Compound for Male Contraception

On By ModernMedia

Researchers have isolated a natural compound found in a Chinese Herb that can reversibly induce male sterility.

The compound, triptonide, can be either purified from a Chinese herb called Tripterygium Wilfordii Hook F, or produced through chemical synthesis. It is being investigated for application in various cancers.

Single daily oral doses of triptonide induce altered sperm having minimal or no forward motility with close to 100% penetrance and consequently male infertility in 3-4 and 5-6 weeks. Fertility is restored within 4-6 weeks, and no toxic effects were observed even over the long term. 

Analysis suggested that triptonide targets one of the last steps during sperm assembly, leading to the production of altered sperm with limited motility.

“Thanks to decades of basic research, which inspired us to develop the idea that a compound that targets a protein critical for the last several steps of sperm assembly would lead to the production of nonfunctional sperm without causing severe depletion of testicular cells,” said Dr Yan. “We are very excited that the new idea worked and that this compound appears to be an ideal male contraceptive. Our results using non-injurious studies on lower primates suggest triptonide will be an effective treatment for human males as well. Hopefully, we will be able to start human clinical trials soon to make the non-hormonal male contraceptive a reality.”

“Dr Yan’s discovery represents a major leap forward in the field,” said Drs Christina Wang and Ronald Swerdloff, who are TLI co-Principal Investigators helping lead NIH-supported advanced clinical trials on hormone-based birth control approaches. “The more contraceptive methods available, the better, as we will want a family of pharmaceutical products to safely and effectively meet the family planning needs of men and couples at different stages of their reproductive lives, with differing ethnic, cultural and religious backgrounds and economic means,” they concluded.

Source: Medical Xpress

Categories : Medical Research & Technology New Compounds and TreatmentsTags :

Combination Nanoparticle Therapy Shows Promise as Antiviral

On By ModernMedia

Researchers have developed a new nanoparticle combination as a broad-spectrum anti-RNA virus treatment. 

The results of their study have been published on the bioRxiv preprint server. Note that as a preprint, this paper has not yet been peer reviewed.
Non-specific antivirals offer a number of attractive advantages. Their broad spectrum activity suppresses mutations, and would they also readily be at hand for future outbreaks. Nanoparticles are one possibility, with reduced toxicity.

Silver nanoparticles (AgNPs) are well-established as antibacterial and antiviral agents, and are the subject of many exotic biomedical applications. The mechanism of AgNPs is thought to be through physiochemical destruction of the microbial surface, with internal disruption from free Ag+ ions and reactive oxide species. Graphene oxide (GO) also has anti microbial properties. With its high surface area, GO also acts as a drug carrier.

The researchers produced seven different material combinations using three different methods: reduction with silver salt, direct addition of Ag nanospheres, and direct addition of Ag nanospheres to thiolised graphene.
To test the materials against seasonal-type infections as well as the kind of virus that could be expected from a future pandemic, the researchers tested the nanoparticles with influenza A virus (IAV) and human coronavirus (HCoV) OC43. IAV is an enveloped virus of the orthomyxovirus family with a segmented single-stranded RNA genome; it causes flu pandemics. HCoV-OC43 is an enveloped betacoronavirus with a single-stranded RNA genome associated with the common cold in humans.

Two of the GO-AgNP materials showed rapid, potent antiviral activity in solution against the viruses. The remaining five materials possessed a range of modest to no antiviral effects against IAV, the researchers reported. They observed a synergistic effect between the AgNPs and GO, with mechanism of action possibly being rapid disruption of the viral envelope. With high levels of antiviral agents, the combination of AgNPs with GO was found to show greater antiviral performance and lower toxicity.

“Our finding that graphene oxide/silver nanoparticle ink can rapidly prevent in vitro infection with two different viruses is exciting, and suggests that the ink has the potential to be used in a variety of applications to help reduce the spread of viruses in the environment,” said co-author Dr Meredith J Crane.

Source: News-Medical.Net

Journal information: Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection in vitro, Meredith J. Crane, Stephen Devine, Amanda M. Jamieson, bioRxiv 2021.02.25.43

Categories : Genetics New Compounds and TreatmentsTags :

Embracing Ethnic Genetic Diversity in Drug Design

On By ModernMedia

Although human beings have a great deal of genetic similarity, small genetic differences can nonetheless lead to very different results in drug effects.

Pharmacologist Namandje Bumpus, PhD—who recently became the first African American woman to head a Johns Hopkins University School of Medicine department, and is the only African American woman leading a pharmacology department in the country—explains why certain drugs can have different effects between distinct populations. Warfarin, for example, is known to be less effective in people of African descent.  

As new vaccines and treatments are developed to fight the COVID pandemic, which have disproportionately affected certain ethnic groups. According to APM Research Lab, in the US as of 2 Feb, Pacific Islanders are 2.7 times as likely to die from COVID as whites (adjusted for age), compared to 0.9 times for Asian Americans.

In light of these differences, Bumpus laid out a four-part plan to improve the equity of drug development.

Merely increasing the representation of races in drug trials is insufficient. Her plan includes: laboratory research to study genetic variability; diversifying the scientific workforce; diversity requirements for funding agencies; and diversity reporting requirements on clinical trial demographics in published articles.

Bumpus said that with genetic technology, animals can be engineered to “bolster predictability of drug outcomes and provide a mechanistic foundation for understanding disparities.”

Genetic variations linked to drug response are often associated with a family of enzymes, cytochromes P450. In humans this enzyme family processes about 75% of clinically available drugs. Subtle genetic differences can however lead to altered enzymes in humans, and these are more common in certain ethnic groups. 

This framework, Bumpus said, could compel the drug development field to move toward a future where “treatments are most likely to work for all people” and “existing health disparities are not further exacerbated.”

Source: Medical Xpress

Journal information: Namandjé N. Bumpus, “For better drugs, diversify clinical trials,” Science  05 Feb 2021: Vol. 371, Issue 6529, pp. 570-571. DOI: 10.1126/science.abe2565

Categories : New Compounds and TreatmentsTags :

Paralysed Mice Walk Again with ‘Designer’ Cytokines

On By ModernMedia

Scientists have sought a means to regenerate spinal cord injuries which leaves patients paraplegic or quadriplegic – and now a breakthrough by researchers at Ruhr-University Bochum, Germany, may see that dream realised.

By the time humans reach adulthood, after an injury they can no longer regenerate the axons which transfer nerve impulses from brain to muscles. In 2013, the researchers discovered that a cytokine called interleukin-6 (IL-6) promoted the regeneration of optic axon fibres in vitro. IL-6 was known to be involved in nerve regeneration as well as in neuropathic pain from peripheral nerve injuries. As promising as this experiment was, delivery of the cytokine to the injury location deep in the body was an obstacles, as was the fact that it had a fairly weak effect on stimulating nerve tissue regrowth.

The team subsequently developed hyper-IL-6, an artificial variant of IL-6 that was far more potent than its natural counterpart. However, the “designer” cytokine still could not be delivered to the injured tissue where it was needed. To get around this, the researchers turned to a somewhat novel delivery method: gene therapy. A few motor neurons in the brain’s sensorimotor cortex are altered via engineered viruses to produce hyper-IL-6, which is then distributed along the axon’s length to the injury site.

“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” explained senior author Dr Dietmar Fischer.

After a single injection of the engineered virus and its hyper-IL-6 payload, mice with severed spinal cords were able to walk again after two to three weeks.

“This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia,” said Dr. Fischer.
Following the success of these experiments, Dr. Fischer’s team is looking at combining the engineered cytokine treatment to other promising applications, such as tissue grafts. Additionally, they are investigating whether the hyper-IL-6 treatment can regenerate spinal cord damage that occurred weeks beforehand.

“This aspect would be particularly relevant for application in humans. We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”

However, adapting this designer cytokine treatment to be one that is safe for humans will take several years.

Source: Medical News Today

Categories : New Compounds and TreatmentsTags :

Antifungal Compound Discovered in Ant Farms

On By ModernMedia

Researchers in Brazil have discovered an antifungal compound by bacteria living in ant farms, which may have medical applications.

In the fungal farms where attine ants tend as their food source, Pseudonocardia and Streptomyces bacteria produce metabolites which shield the crop against pathogens. Curiously, these metabolites vary across geographic locations.

Attine ants are a type of ant which grow and harvest fungus for food, and are only found in the Western Hemisphere. They first evolved from a common Amazonian ancestor some 50 million years ago, giving rise to some 200 species of ants spread across South and Central America, which share common farming practices. The bacteria at these farms have a symbiotic relationship where they defend against fungi such as Escovopsis in exchange for food.

These metabolites vary considerably, suggesting a fragmented history. Searching a number of ant nests spread across a large geographical area, the researchers discovered that two thirds of the Pseudonocardia strains were producing the same metabolite. They named this newly discovered metabolite attinimicin.The study was the first one where a common, specialised metabolite produced by ant-associated bacteria was found across geographic locations.

Attinimicin inhibited fungal parasites while not harming the fungal crop, but only in the presence of iron. It proved as effective in treating Candida albicans infections in mice as a clinically used azole-containing antifungal. This means that the metabolite could have clinical applications. Attinimicin was shown to have a similar structure to two other metabolites produced by Streptomyces, suggesting the responsible genes have a common evolutionary origin.

Source: News-Medical.Net

Journal information: Fukuda, T.T.H., et al. (2021) Specialized Metabolites Reveal Evolutionary History and Geographic Dispersion of a Multilateral Symbiosis. ACS Central Science. doi.org/10.1021/acscentsci.0c00978.

Categories : New Compounds and Treatments Skeletal SystemTags :

Osteoporosis Drug Enhances Natural Bone Formation

On By ModernMedia

A new osteoporosis drug, NaQuinate, that treats osteoporosis by enhancing its response to weight bearing, has completed its first human clinical trial. 

NaQuinate is a naphthoquinone carboxylic acid, and is found naturally as a Vitamin K metabolite. It has been shown in mouse models that NaQuinate responds synergistically to mechanical loading, building bone density. In a separate trial, the efficacy of NaQuinate is being evaluated against that of bisphosphonates without loading and anabolics with loading.

Haoma Medica’s Chief Medical Officer, Dr Cenk Oguz, said: ”We are delighted that the first-in-human study has completed its last dosing. There were no significant safety or tolerability concerns up to the highest doses tested which underlines our expectation that NaQuinate is safe and well tolerated.”
Haoma Medica’s CEO,  Dr Steve Deacon, said:”Our pre-clinical research has revealed an exciting feature of NaQuinate where it appears to have the capacity to work in harmony with the body’s natural response to weight bearing exercise to synergistically enhance bone formation when and where required – now that would be a ‘smart’ drug. Together with the safety data from this first-in-human study, this supports the potential that NaQuinate treatment could provide a safe, novel and smart therapeutic approach to bone disorders like osteoporosis and better maintain healthy skeletal aging.”

Source: PR NewsWire