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Brain surgeons’ research prompts new approach to cancer treatment

 

Reporter: Alex Crystal

 

UPDATED on 5/22/2019

For treating high-grade gliomas, an aggressive brain cancer, the combination therapy of experimental agents Toca 511 [immunotherapy] and Toca FC [chemotherapy] failed against chemotherapy or Avastin to show extended survival

  • Tocagen said Tuesday its brain cancer trial has not been able to show so far that a combination therapy of experimental agents Toca 511 and Toca FC extended survival when compared with chemotherapy or Avastin. The announcement was based on an interim analysis and the study will proceed to a final readout later this year.
  • Investors took the announcement as a sign that the trial is likely to fail, as shares fell 35% Wednesday to a record low. SVB Leerink analyst Daina Graybosch raised questions about the biological effect of the combination therapy as well as earlier-stage trial designs that Tocagen used to justify moving swiftly into a pivotal trial.
  • Toca 511, an immunotherapy, and Toca FC, a chemotherapy, aim to treat high-grade gliomas, an aggressive brain cancer. In the recurrent patients Tocagen hopes to treat, average survival is no more than about a year.

SOURCE

https://www.biopharmadive.com/news/tocagen-brain-cancer-trial-continues-stock-drop/555360/

 

Brain surgeons turn to basic science to fight childhood brain cancer @Stanford Medical School

By Krista Conger

 

Residents Teresa and Jamie Purzner stepped away from Neurosurgery to focus on research of medulloblastoma. The pair spent six years researching the cause of brain tumors before publishing their findings. They discovered a phosphate-adding protein called CK2 linked to the growth of this type of cancer. Afterword, they applied this finding by putting a CK2 inhibitor in mice implanted with medulloblastoma cells. After successful trials on animals, the duo combined efforts with the Stanford SPARK program to begin the development of drugs. Their efforts were rewarded and the pair went ahead with phase 1-2 clinical trials of the only known CK2 inhibitor, CX-4945. It is yet to be seen how successful their efforts will be in treating children with hedgehog-dependent medulloblastoma, but this approach opens up an entirely new and promising field of research.

SOURCE

http://med.stanford.edu/news/all-news/2019/05/brain-surgeons-turn-to-basic-science-to-fight-childhood-brain-cancer.html

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Lab on a chip Enters a New Field

Reporter: Irina Robu, PhD

The basis of the lab-on-a-chip is to integrate thousands of biochemical operations onto a single chip that could be done by splitting a single drop of blood collected from the patient in order to get a precise diagnosis of potential diseases. Research on lab-on-a-chip primarily focuses on human diagnostics and DNA analysis. Miniaturization of biochemical operations normally handled in a laboratory has numerous advantages, such as cost efficiency, diagnostic speed and sensitivity. The emergence of the lab-on-a-chip field mainly relies on two core technologies: microfluidics and molecular biology.

The team led by Govind Kaigala at IBM Research-Zurich and the group of Moran Bercovici at Technion-Israel Institute of Technology designed a new device that can effectively control liquids and materials on the micro-scale and have demonstrated that the key to dynamic control of fluid mechanics may be electric. Their research is published on Proceedings of the National Academy of Sciences.

The research team turned to electric field to control the control the motion of fluid in a way that is adjustable. When liquid contacts a surface, it develops a layer of charge; applying an electric field to this layer moves the charges, dragging the liquid with them and creating a net flow.

Using this knowledge, the team calculated a device that uses disk-shaped electrodes implanted in the bottom of a fluidic chamber to produce dipole-like flow patterns in the liquid when an electric field is applied. Placing multiple electrodes together in an array generates “virtual channels” that guide the fluid stream. By altering the voltages on the electrodes, they could then reverse the pattern to create an inner region of flow bounded by an outer region of stagnation, which is useful for selective on-demand mixing. While more applications of these flow patterns have yet to be explored, the control and flexibility the team’s device offers recommend that the lab-on-a-chip dream may finally be within grasp.

SOURCE

https://physicsworld.com/a/microfluidics-enters-a-new-field/


The Journey of Antibiotic Discovery

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

The term ‘antibiotic’ was introduced by Selman Waksman as any small molecule, produced by a microbe, with antagonistic properties on the growth of other microbes. An antibiotic interferes with bacterial survival via a specific mode of action but more importantly, at therapeutic concentrations, it is sufficiently potent to be effective against infection and simultaneously presents minimal toxicity. Infectious diseases have been a challenge throughout the ages. From 1347 to 1350, approximately one-third of Europe’s population perished to Bubonic plague. Advances in sanitary and hygienic conditions sufficed to control further plague outbreaks. However, these persisted as a recurrent public health issue. Likewise, infectious diseases in general remained the leading cause of death up to the early 1900s. The mortality rate shrunk after the commercialization of antibiotics, which given their impact on the fate of mankind, were regarded as a ‘medical miracle’. Moreover, the non-therapeutic application of antibiotics has also greatly affected humanity, for instance those used as livestock growth promoters to increase food production after World War II.

 

Currently, more than 2 million North Americans acquire infections associated with antibiotic resistance every year, resulting in 23,000 deaths. In Europe, nearly 700 thousand cases of antibiotic-resistant infections directly develop into over 33,000 deaths yearly, with an estimated cost over €1.5 billion. Despite a 36% increase in human use of antibiotics from 2000 to 2010, approximately 20% of deaths worldwide are related to infectious diseases today. Future perspectives are no brighter, for instance, a government commissioned study in the United Kingdom estimated 10 million deaths per year from antibiotic resistant infections by 2050.

 

The increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures – platforms – that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines.

 

The increase in drug-resistant pathogens is a consequence of multiple factors, including but not limited to high rates of antimicrobial prescriptions, antibiotic mismanagement in the form of self-medication or interruption of therapy, and large-scale antibiotic use as growth promotors in livestock farming. For example, 60% of the antibiotics sold to the USA food industry are also used as therapeutics in humans. To further complicate matters, it is estimated that $200 million is required for a molecule to reach commercialization, with the risk of antimicrobial resistance rapidly developing, crippling its clinical application, or on the opposing end, a new antibiotic might be so effective it is only used as a last resort therapeutic, thus not widely commercialized.

 

Besides a more efficient management of antibiotic use, there is a pressing need for new platforms capable of consistently and efficiently delivering new lead substances, which should attend their precursors impressively low rates of success, in today’s increasing drug resistance scenario. Antibiotic Discovery Platforms are aiming to screen large libraries, for instance the reservoir of untapped natural products, which is likely the next antibiotic ‘gold mine’. There is a void between phenotanypic screening (high-throughput) and omics-centered assays (high-information), where some mechanistic and molecular information complements antimicrobial activity, without the laborious and extensive application of various omics assays. The increasing need for antibiotics drives the relentless and continuous research on the foreground of antibiotic discovery. This is likely to expand our knowledge on the biological events underlying infectious diseases and, hopefully, result in better therapeutics that can swing the war on infectious diseases back in our favor.

 

During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.

 

References:

 

https://www.mdpi.com/2079-6382/8/2/45/htm

 

https://www.ncbi.nlm.nih.gov/pubmed/19515346

 

https://www.ajicjournal.org/article/S0196-6553(11)00184-2/fulltext

 

https://www.ncbi.nlm.nih.gov/pubmed/21700626

 

http://www.med.or.jp/english/journal/pdf/2009_02/103_108.pdf

 


World’s first artificial pancreas

Reporter: Irina Robu, PhD

Diabetes is a life-long condition where your body does not produce enough insulin (Type 1) or your body cannot use the insulin it has effectively. Since there is no cure for diabetes, the artificial pancreas system comes as a relief for patients that are suffering with this disease.

The artificial pancreas, MiniMed 670G hybrid closed loop system designed by Medtronic is the first FDA-approved device that measures glucose levels and delivers the appropriate dose of basal insulin. The system comprises Medtronic’s MiniMed 670G insulin pump that is strapped to the body, an infusion patch that delivers insulin via catheter from the pump and a sensor which measures glucose levels under the skin and can be worn for 7 days at a time. While the device regulates basal, or background, insulin, patients must still manually request bolus insulin at mealtimes.

The device is intended for people age 14 or older with Type 1 diabetes and is intended to regulate insulin levels with “little to no input” from the patient. The artificial pancreas measures blood sugar levels using a constant glucose monitor (CGM) and communicates the information to an insulin pump which calculates and releases the required amount of insulin into the body, just as the pancreas does in people without diabetes.

The 2016 FDA approval was done in just three months which is a record for any medical device. The agency evaluated data from a clinical trial in which 123 patients with Type 1 diabetes used the system’s hybrid closed-loop feature as repeatedly during a three-month period. The trial presented the device to be safe for use in those 14 and older, showing no serious adverse events. The system is on sale since spring 2017.

While further clinical research is needed to ensure that the strength of the device in different settings is consistent, several researchers support the view that “artificial pancreas systems are a safe and effective treatment approach for people with type 1 diabetes. Medtronic counts this device as a step toward a fully automated, closed-loop system.

SOURCE

https://www.fiercebiotech.com/medical-devices/fda-approves-medtronic-s-artificial-pancreas-world-s-first


Alter the Code of Life – Technologies for Gene Editing from MammothBiosciences, San Francisco, CA

 

Reporter: Aviva Lev-Ari, PhD, RN

 

 

https://mammoth.bio/

Mission

Mammoth’s vision is to provide a CRISPR-based platform on which an infinite number of tests can be built by both ourselves and our partners – democratizing access to an endless variety of tests for bio sensing in healthcare, as well as across industries such as agriculture, manufacturing, forensics, and more.

CRISPR Is Programmable

Both Cas12 and Cas13 are programmed by a molecule called a guide RNA. This RNA molecule matches up with the sequence we want to detect and the protein senses that a match has been found.
Reprogramming these complexes is as simple as changing the sequence of the guide RNA.

Building the CRISPR platform foundation – The Team

With expertise spanning the intersection of data analytics and molecular biology, Mammoth is building on the pioneering research conducted in Jennifer Doudna’s lab at UC Berkeley to build the CRISPR platform for the world’s best detection products.

  • Jennifer Doudna
    Co-founder, Chair of Scientific
    Advisory Board
  • Trevor Martin
    Co-founder, CEO
  • Lucas Harrington
    Co-founder, Chief Discovery Officer

SOURCE

https://mammoth.bio/

 

Other 150 related articles on CRISPR published in this Open Access Online Scientific Journal include the following:

 

UPDATED – Gene Editing Consortium of Biotech Companies: CRISPR Therapeutics $CRSP, Intellia Therapeutics $NTLA, Caribou Biosciences, ERS Genomics, UC, Berkeley (Doudna’s IP) and University of Vienna (Charpentier’s IP), is appealing the decision ruled that there was no interference between the two sides, to the U.S. Court of Appeals for the Federal Circuit, targeting patents from The Broad Institute.

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/04/13/gene-editing-consortium-of-biotech-companies-crispr-therapeutics-crsp-intellia-therapeutics-ntla-caribou-biosciences-and-ers-genomics-uc-berkeley-doudnas-ip-and-university-of-vienna-charpe/

 

Top 10 CRISPR Podcasts Every Scientist (& Non-Scientist) by Synthego.com

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/03/09/top-10-crispr-podcasts-every-scientist-non-scientist-by-synthego-com/

 


A. Richard Newton Distinguished Innovator Lecture Series – Dr. Jennifer Doudna, April 23, 2019, UC, Berkeley

 

FEATURED SPEAKERS

Last month, Dr. Jennifer Doudna spoke with the Sutardja Center at the A. Richard Newton Distinguished Innovator Lecture Series. Dr. Doudna is a UC Berkeley Professor,  co-inventor of CRISPR and co-author of A Crack in Creation and cofounder of Mammoth Biosciences; Caribou Biosciences; Intellia Therapeutics and Editas Medicine. Whether or not your passion is bio-tech, this lecture will be relevant to all of us, since the innovations in gene editing technology will change our lives.

Dr. Doudna recently wrote in an article for Time’s most influential people… “Since 2012, when CRISPR-Cas9 transformed research, scientists have purposely taken a cautious and deliberate approach, focusing on how to safely apply genome editing to cure genetic diseases, fight cancer, accelerate drug development, create transplant organs and develop more nutritious crops. Its potential to improve our lives is enormous. But its potential to harm, with unintended side effects, is still unknown.”

Click here or the picture above to watch the full video!

WATCH VIDEO

A. Richard Newton Distinguished Innovator Lecture Series – Dr. Jennifer Doudna, April 23, 2019, UC, Berkeley

https://www.youtube.com/watch?v=-vuoNML-u6I&feature=youtu.be&utm_source=Sutardja+Center+Contacts&utm_campaign=b28e42ec1a-EMAIL_CAMPAIGN_2019_04_18_06_13_COPY_01&utm_medium=email&utm_term=0_8ae9d85a8f-b28e42ec1a-164676973

 

 

SOURCE

From: Sutardja Center for Entrepreneurship & Technology <sidhu@berkeley.edu>

Reply-To: Sutardja Center for Entrepreneurship & Technology <sidhu@berkeley.edu>

Date: Thursday, May 16, 2019 at 12:00 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Dr. Jennifer Doudna, co-inventor of CRISPR and UC Berkeley professor, speaks at the Sutardja Center


One or More Clinical Trials to get FDA Approve a Drug?

 

Reporter: Aviva Lev-Ari, PhD, RN

Almost half of all new drug approvals in 2018 relied on one clinical trial

SOURCE

https://endpts.com/almost-half-of-all-new-drug-approvals-in-2018-relied-on-one-clinical-trial/?utm_medium=email&utm_campaign=726%20JJ%20has%20a%20new%20list%20of%20blockbusters-to-be%20it%20wants%20you%20to%20know%20about%20Top%20Biogen%20exec%20jumps%20ship&utm_content=726%20JJ%20has%20a%20new%20list%20of%20blockbusters-to-be%20it%20wants%20you%20to%20know%20about%20Top%20Biogen%20exec%20jumps%20ship+CID_15fe600050d8a9e0e22fba39d1651c9a&utm_source=ENDPOINTS%20emails&utm_term=Almost%20half%20of%20all%20new%20drug%20approvals%20in%202018%20relied%20on%20one%20clinical%20trial