Top 10 Biopharma News Stories of 2019
There have been many exciting developments in the biopharma research field this year. Here, we revisit the top 10 most-read biopharma news stories of 2019 at Technology Networks.
Discovery of New Liver Cell Could Mean Liver Transplants Become Redundant
In July of this year, scientists from King's College London published a study outlining their discovery of a novel type of cell: hepatobiliary hybrid progenitor (HHyP) cells. Despite these cells forming during early development in the womb, the study identified that they also persist in smaller quantities in adults, and that they can grow into the main two types of adult liver cells: hepatocytes and cholangiocytes.
The team of researchers analyzed HHyPs and discovered that they resemble stem cells which have been shown to rapidly repair mice liver following injury. Such injury might be cirrhosis, in which scarring of the liver can eventually lead to liver failure.
Liver disease can prove extremely debilitating for a patient and, in the most severe cases, a liver transplant is the only viable treatment option. Of course, a liver transplant in itself is a major life-changing surgery that runs its own risk of complications. The need for donor organs also greatly outweighs the increasing demands.
How might this research make a difference? Dr Tamir Rashid from the Centre for Stem Cells and Regenerative Medicine explains: "For the first time, we have found that cells with true stem cell-like properties may well exist in the human liver. This, in turn, could provide a wide range of regenerative medicine applications for treating liver disease, including the possibility of bypassing the need for liver transplants."
Published in: Nature Communications
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How Viagra Could Transform Bone Marrow Transplants
Each year, over 25,000 hematopoietic stem cell transplantations (HSCTs) are performed as a curative treatment for conditions such as lymphoma, leukemia, hemoglobinopathies, myelodysplastic and myeloproliferative syndromes.
HSCs are characterized by their ability to self-renew and differentiate into all mature blood lineages. Their transplantation to treat the aforementioned syndromes involves replacing abnormal blood-forming stem cells with healthy cells. Currently, multi-day injections of the pharmacological agent granulocyte-colony stimulating factor, or G-CSF, are used to encourage stem cell mobilization from the bone marrow to the blood stream. This approach is limited by adverse effects such as fatigue, bone pain and nausea, and is therefore unsuitable for certain patients.
A study published by Camilla Forsberg's lab explored whether Viagra might be a viable option for HSCT to help overcome the issue of stem cell mobility. A vasodilator, Viagra was first developed to treat patients with high blood pressure, heart disease, and associated vascular disorders.
In a mouse study, the scientists found that three days of oral Viagra, when combined with a single injection of Plerixafor, resulted in an 8.4-fold increase in HSCs compared to control mice.
The stem cells were transplanted into recipient mice, and the scientists found that a combination of Plerixafor and Viagra resulted in the long-term engraftment of functional, self-renewing, multipotent hematopoietic stem cells. The results of the study therefore suggest that this approach may be a suitable option for HSCT in patients.
"Given that both drugs are FDA approved, they could be relatively quickly tested in human volunteers," says Forsberg, a stem cell biologist at the University of California, Santa Cruz. If proven safe and effective in human clinical studies, "Clinicians could consider these findings when selecting treatment strategies for their patients and for volunteer donors of hematopoietic cells used in transplantation therapies."
Published in: Stem Cell Reports
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Vaccine Has "Almost Wiped Out" Cervical Pre-cancer
A vaccine given to schoolgirls in Scotland to protect them from cervical pre-cancer has almost wiped out the disease, according to research involving the University of Strathclyde. The study of the vaccine against human papillomavirus (HPV) has found a reduction of nearly 90% in the cancer-causing virus since the treatment was brought into Scottish schools a decade ago.
The research assessed 140,000 women who received their first cervical screen between 2008 and 2016. It showed a reduction of up to 90% in cervical disease abnormalities – pre-cancerous cells.
The data are consistent with the reduced circulation of high-risk HPV infection in Scotland and confirm that the HPV vaccine should significantly reduce cervical cancer in the next few years; cervical cancer cases in women aged 20-24 have already reduced by 69% since 2012.
Published in: British Medical Journal
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Secrets of Herbal Antidepressant Synthesis Are Uncovered
The historical use of the herb St. John's Wort (known botanically as Hypericum perforatum) as a medicinal compound is well documented, and includes its recommended use as a diuretic, wound-healing herb, treatment for menstrual pain, and as a cure for snakebites by Greek physicians of the first century.
Despite its long-standing use in both traditional and modern medicine, our understanding of how one of the key active metabolites in St. John's Wort, hypericin, is produced, is incomplete. Hypericin is synthesized and stored in the dark glands of St. John's Wort, but the precise mechanisms and processes involved in synthesis remain to be clarified.
The research team in this study, led by Paride Rizzo from the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, adopted a different approach. They focused on the glands of St. John's Wort, stating in the paper that "Understanding which genes are involved in dark gland development and hypericin biosynthesis is important for the development of new Hypericum extracts that are highly demanded for medical applications."
The scientists phenotyped 93 Hypericum-accessions and discovered a polymorphism which resulted in glanded and glandless phenotypes in the placental tissue of the sample. Focusing on the placental tissue, they then identified two transcription factors whose expression was "strictly synchronized" with the differentiation of the dark glands.
Published in: Plant Biotechnology Journal
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Green Tea Acts as a "Remote Control" To Switch on Cell Therapy
Engineered cell therapies, deemed the "next frontier" in modern medicine, contain specific cellular material that triggers a desired effect in vitro or in vivo. Such therapies are in development in laboratories across the globe for an array of different conditions, including acute myocardial infarction (heart attack), brain cancer, breast cancer, diabetes and liver diseases. They offer a novel avenue of therapeutics for patients suffering from diseases for which treatment options are limited.
For their efficacious and safe use in the clinic, scientists need to be able to regulate the activity of these cells in vivo. Essentially, they require a "remote control". This has proven a major barrier for the delivery of cell therapies to patients. Initial work in this field has adopted antibiotics such as doxycycline or tetracycline as remote-control triggers for gene expression in the cells. However, regular use of antibiotics may result in antibiotic resistance and other adverse side effects.
Post green-tea consumption, tea catechins and phenolic acids undergo metabolic processing to form the antioxidant protocatechuic acid (PCA). In this study, researchers utilized this antioxidant as a "remote control" for activating gene switches in cells. "PCA is a major tea catechin compound produced by humans following green tea consumption that has powerful antioxidant activity. Therefore, in this study, we showed the use of protocatechuic acid (we call it PCA), a metabolite after tea drinking, as a trigger molecule," Haifeng Ye, Professor at East China Normal University told Technology Networks.
Published in: Science Advances
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Transplanted Brain Stem Cells Survive in Mice Without Anti-rejection Drugs
A rare yet devastating class of genetic diseases in which myelin, the coating that protects neurons and aids in neurotransmission, does not form properly, affect 1 in every 100,000 children born in the U.S. Being able to transplant healthy cells into the brain successfully without the need for anti-rejection drugs would majorly advance therapeutics in this area.
In September of this year, Johns Hopkins Medicine researchers published a study in which they developed a novel way to successfully transplant certain protective brain cells without the need for lifelong anti-rejection drugs.
To stop the immune system's "go" signal, the researchers used two antibodies: CTLA4-Ig and anti-CD154, which prevent T cells from attacking when encountering a foreign particle. This combination of antibodies had been explored previously in solid organ transplants in animals, but had not been tested for cell transplants to repair myelin in the brain.
The team of scientists, led by Piotr Walczak, injected mouse brains with protective glial cells that produce the myelin sheath. These cells had been genetically engineered to glow so that the researchers could visualize them. The glial cells were transplanted into three types of mice: mice genetically engineered to not form the glial cells that create the myelin sheath, normal mice and mice bred to be unable to mount an immune response. The antibodies were then applied to block the immune response for six days.
Walczak and team found that the transplanted cells were able to thrive and assume their normal physiological function of protecting neurons in the brain, without anti-rejection drugs. The scientists did, however, note that these results are preliminary.
Published in: Brain
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41% of Parents May Seek New Provider Because of Unvaccinated Children at Their Doctor’s Office
Four in 10 parents say they are very or somewhat likely to move their child to a different provider if their doctor sees families who refuse all childhood vaccines, according to a new national poll.
Most American children receive recommended vaccines protecting them from dangerous illnesses like measles and whooping cough. But doctors sometimes care for children whose parents refuse vaccines against providers' recommendations. And that is not news many parents of vaccinated children want to hear, suggests the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.
Three in 10 parents polled say that their child's primary care office should ask parents who refuse all vaccines to find another health provider.
The report is based on responses from 2,032 parents of at least one child 18 or under. The poll also found that many parents are unaware of policies in their child's primary care office regarding unvaccinated children.
Full report available here.
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"MOSAIC" HIV Vaccine to be Tested in Thousands Globally
In August, it was announced that 3,800 individuals from eight countries across the globe would embark on a Phase III clinical trial of an experimental human immunodeficiency virus (HIV) vaccine, Mosaico.
The latest statistics show that in 2018, approximately 1.7 million people were newly infected with HIV, 37.9 million people were living with HIV and 770,000 people died of an AIDS-related illness.
A UNAIDS report published in July detailed that key populations — people who inject drugs, gay men and other men who have sex with men, transgender people, sex workers and prisoners—accounted for around 95% of new HIV infections in Eastern Europe and Central Asia and in the Middle East and North Africa in 2018. Mosaico will target such populations, recruiting cis-gender men and transgender individuals who have sex with cis-gender men and/or transgender individuals to test the vaccine.
The announcement of the trial's commencement could not be more pertinent considering the same report also expressed concerns that the pace of progress in reducing new HIV infections, increasing access to treatment and ending AIDS-related deaths is slowing down.
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Sleeping Beauty Awakens to a Makeover and a Job in Genome Engineering
A transposon is a sequence of DNA that is able to move around and change its position within a genome. They can be used to change a cell's genetic identity by introducing genes and creating or reversing mutations, making them an efficient tool for genome engineering.
The transposon system comprises a transposase protein that binds to the end of the transposon. The transposase can be encoded by the transposon gene or it can be supplied by another source. When the transposase is supplied externally, it is known as "non-autonomous". This type of transposase is the most useful for genetic engineering, as once they are inserted, they cannot work independently and continue to re-insert themselves, providing scientists with control over the genome.
The DNA transposons that have been identified in the human genome are all non-autonomous, as, despite the fact they contain transposase genes, the genes are not functional and cannot encode a transposase that is able to mobilize the transposon.
The Sleeping Beauty transposon system comprises a Sleeping Beauty transposase that was "resurrected" from inactive copies in fish genomes in 1997. It was designed to insert specific sequences of DNA into the genomes of vertebrate animals and has been used for many applications, including gene therapy.
In this study, scientists created a novel variant of the Sleeping Beauty transposase. This variant possesses improved biochemical properties, which the researchers suggest will enable direct use of the protein for genome modification. "The protein we developed can be delivered into mammalian cells and remains fully functional, enabling efficient and stable genome modifications in target cells on demand," explains Orsolya Barabas, group leader at EMBL Heidelberg.
Published in: Nature Biotechnology
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EMBL spins the Sleeping Beauty transposase. Credit: Scienseed.
New CAR T-Cell Therapy for Blood Cancer Relapse Patients Could Be in Clinical Trials Within Six Months
Currently, two chimeric antigen receptor T-cell (CAR T-cell) therapies are approved for use in the United States: Kymriah® (tisagenlecleucel) and Yescarta® (axicabtagene ciloleucel). Both therapies were designed to treat different forms of blood cancer, with Kyrmiah® targeting B-cell acute lymphoblastic leukemia (B-ALL) in people ages >25 years whose malignancies have not responded to other forms of treatment, and Yescarta® for adults with B-cell cancers that have also not responded to conventional treatment.
Whilst some patients show a robust response to CAR T-cell therapy, some patients can experience relapses. Particularly in B-cell malignancies, up to 30% of patients experience relapse. This can occur when a patient's cancer cells stop expressing the CD19 target. In a new study, scientists developed CAR T cells that target an alternative B cell-specific surface marker – B-cell activating factor receptor (BAFF-R).
In this study, the researchers tested BAFF-R directed CAR T cells against human lymphoma and acute lymphocytic leukemia cell lines in vitro and in mouse models. They compared this approach with the CD19-directed CAR T cells, and particularly focused on the effect of BAFF-R-CAR T-cell therapy against CD19 negative targets. The authors found that BAFF-R-directed CAR T cells applied in mice with human lymphoma cells resulted in complete tumor regression and 100% long-term survival in the animals.
Published in: Science Translational Medicine
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Active Component of "Holy Herb" a Neuroprotective Candidate
The medicinal powers of aspirin, digitalis, and the anti-malarial artemisinin all come from plants. The discovery of a potent neuroprotective and anti-inflammatory chemical in a native California shrub has been raised as a potential therapeutic candidate.
To identify natural compounds that might reverse neurological disease symptoms, Pamela Maher and team at Salk’s Cellular Neurobiology Laboratory applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The lab had previously used this approach to identify other chemicals (called flavonoids) from plants that have anti-inflammatory and neuroprotective properties.
Through the screen, the lab identified a molecule called sterubin as Yerba santa’s, also known as the "holy herb" most active component. The researchers tested sterubin and other plant extracts for their impact on energy depletion in mouse nerve cells, as well as other age-associated neurotoxicity and survival pathways directly related to the reduced energy metabolism, accumulation of misfolded, aggregated proteins and inflammation seen in Alzheimer’s. Sterubin had a potent anti-inflammatory impact on brain cells known as microglia. It was also an effective iron remover—potentially beneficial because iron can contribute to nerve cell damage in aging and neurodegenerative diseases. Overall, the compound was effective against multiple inducers of cell death in the nerve cells, according to Maher.
Published in: Redox Biology
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GM Chickens Could Lay Your Medicine
Chickens that are genetically modified to produce human proteins in their eggs can offer a cost-effective method of producing certain types of drugs, research suggests.
The study – which has initially focused on producing high quality proteins for use in scientific research – found the drugs work at least as well as the same proteins produced using existing methods. High quantities of the proteins can be recovered from each egg using a simple purification system and there are no adverse effects on the chickens themselves, which lay eggs as normal.
The team have initially focused on two proteins that are essential to the immune system and have therapeutic potential – a human protein called IFNα2a, which has powerful antiviral and anti-cancer effects, and the human and pig versions of a protein called macrophage-CSF, which is being developed as a therapy that stimulates damaged tissues to repair themselves.
Just three eggs were enough to produce a clinically relevant dose of the drug. As chickens can lay up to 300 eggs per year, researchers say their approach could be more cost-effective than other production methods for some important drugs.
Researchers say they haven’t produced medicines for use in patients yet, but the study offers proof-of-principle that the system is feasible and could easily be adapted to produce other therapeutic proteins.
Published in: BMC Biotechnology
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