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Antisense-ing Alzheimer’s

in Reporting from the Lab by

Enhanced life expectancy has led to a rise in aging associated disorders such as Alzheimer’s disease (AD). Two important pathological hallmarks of AD include the appearance of Beta amyloid plaques and neurofibrillary tangles (NFT) in the brain. The abnormal clustering of beta amyloid protein between neurons forms beta amyloid plaques. NFT’s occur as a result of aggregates formed by Tau, a protein molecule critical for microtubule stability and axonal transport. Both these processes lead to the disruption of neuronal communication subsequently leading to neuronal damage and loss.

While the current treatment options correct the cognitive symptoms of the disease, there is a quest to target specific underlying disease mechanisms. In a fascinating study in Science Translational Medicine, researchers DeVos et al suggest the use of an antisense oligonucleotide (ASO) to decrease the accumulation of the misfolded Tau proteins in the brain as well as to reverse the deposition of Tau in older mice.

In this paper, the authors designed an ASO that can specifically target human tau and reduce its expression. ASOs are synthetic single stranded nucleotides that bind to complementary mRNA or precursor pre-mRNA (transcript that undergoes splicing or other modifications) and consequently inhibit or reduce protein expression or modify protein function. For this study, the researchers used a transgenic PS19 mouse that expresses a mutant P301S human Tau protein responsible for the development of AD in these mice. Upon administration of a synthetic ASO targeting human Tau protein in the brains of these mice, the expression of human Tau protein was significantly reduced. Additionally, in order to determine whether treatment with ASO can be used to prevent the toxic accumulation of Tau proteins, they administered the ASO at 6 months of age and examined the levels of Tau protein in the brain at 9 months of age. Interestingly, treated mice showed significantly reduced Tau levels, suggesting the ability of the ASO to prevent Tau-associated pathology, as the mice got older. The researchers further demonstrated that NFT accumulation observed in 9 month old mice can be reversed upon ASO treatment, underscoring the therapeutic ability of these ASOs. AD progression is brought about by the propagation of Tau proteins within the brain. This ability of pathologic Tau to misfold naïve Tau was also reduced upon treatment with ASO. Ultimately, treatment with the ASO increased survival of these mice without causing any decline in their ability to complete a functional task such as building a nest, which is used as a common measure of cognition, social behavior and motor capabilities in mice.

These in vivo preclinical studies were further supported by studies in non-human primates, Cynomolgus monkeys. As Tau proteins are naturally occurring within the nervous system, the researchers showed that ASO treatment reduces the endogenous Tau levels in the brain and spinal cord of these monkeys. Further, the levels of Tau within the cerebrospinal fluid (CSF) can be used as a surrogate marker of treatment efficacy as the levels of Tau in the CSF correlated directly with reduction in protein level within the brain of ASO-treated monkeys.

A major limitation in the treatment of current Tau pathologies is the inability to reverse the damage that has already occurred by these aggregates. In this regard, one of the most remarkable features of this study is the ability of the human Tau ASO to not just prevent but also reverse the Tau pathologies observed in the PS19 mouse. The advancement to clinical trials requires further studies to establish its efficacy in clearing Tau aggregates without affecting general cognitive functions in humans. In the current study, ASO was administered by the surgical placement of an osmotic pump in the brain of mice. However, it is critical to identify feasible and safe mechanisms of delivery of ASOs to the central nervous system of patients. This has been an ongoing area of research for several neurological disorders.

ASOs have been studied extensively as therapeutic molecules for various disorders especially devastating neurodegenerative diseases such as Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS). A recent breakthrough in the ASO therapeutic field came about with the FDA approval of Biogen and Ionis pharmaceuticals’ Nusinersen, an ASO to treat SMA, a debilitating disease affecting children. An ASO (BIIB067) that disrupts the production of misfolded proteins produced by the mutant SOD1 gene in ALS is also in clinical trials. In partnership with Roche, Ionis is also conducting clinical trials with an ASO (ASO-HTT-Rx) which can reduce the levels of Huntingtin protein in Huntington’s disease.

AD is in dire need of a significant drug molecule that targets specific pathogenic activity and not just the symptoms of the disease. Unfortunately, promising candidates that prevent the formation of Beta amyloid plaques, such as Pfizer and Johnson & Jonhsons’ bapineuzumab, Eli Lilly’s solanezumab and Merck’s verubecestat have failed clinical trials. Despite these setbacks, companies continue to investigate novel therapies to fight this disease. Preclinical studies in this paper with an ASO that reduces Tau protein levels can transform Alzheimer’s therapeutic landscape.

Journal article:

DeVos SL et al. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy, Science Translational Medicine. DOI:10.1126/scitranslmed.aag0481

Additional newsfeed:

http://www.thescientist.com/?articles.view/

http://www.sciencemag.org/news

https://www.alz.org/research/science/

https://www.eurekalert.org/pub_releases/

https://www.newscientist.com/article/2119254

Photo source: 

www.alzheimersreadingroom.com

Edited by Isha Verma 

About the author 

Radhika completed her PhD from Cornell University and is currently a Postdoctoral fellow at the Brigham and Women’s Hospital. Her research interests have centered around oncology and neuroimmunology. Among other things, she is striving to effectively communicate scientific discoveries to the community.

 

 

 

 

 

 

The week that it was – 23rd to 30th April, 2017

in ClubSciWri by
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The week in the scientific community has been hugely highlighted with plans and meetings around ensuring that the March for Science momentum doesn’t fizzle out. And communication of unaltered facts has clearly gathered a lot of attention and has been rightly prioritized. Wikipedia co-founder Jimmy Wales launches Wikitribune to provide ‘correct facts’. University of Split, Croatia and Rita Allen Foundation with WGBH could not have been better in timing the announcement of their Summer School in Science Communication and fellowship in science communication, respectively. Plos Pathogens has started a new series – Research Matters – for researchers to write how their fundamental research matters. NASA goes public with its 104,000 pictures, videos and audio files. The European Research Council is actively gathering data from researchers in Europe as well as outside to know how to get the community more engaged in publishing in open access journals. Mozilla has offered paid fellowships for 10 months to train those with ideas in open access science and help them materialize their ideas. Chan Zuckerberg Initiative has joined hands with BioArxiv (the open access repository for life science research from Cold Spring Harbor Laboratory). On a local scale, initiatives like Pint of Science and Pune drunk on Science (details available on Facebook, at the moment) are gaining popularity. After all, open access to science is going to be beneficial to all – lay public to entrepreneurs and industrialists.

Another benefit of having science in open repositories will also help in better peer review. The current way of evaluating research is killing the risk appetite among researchers, limiting scientific progress. It becomes imperative to discuss this now as Springer decided to retract 107 of its papers from Tumor Biology for being published with ‘fake reviews’. On the other hand, the field of oncology is also going through one of its most exciting times – Nanoparticle vaccine for immunotherapy, to target multiple types of cancers, developed by researchers at UT Southwestern, is the talk of the town now. And for novices in this area, you can’t miss the overview of the exciting and inspiring development of this field, from Allison and Sharma‘s eyes, the successful couple of the field.

Potentially entrepreneurial ideas are regularly being churned out of IITs, with IIT Madras this time, developing a hand glove to study the hand kinematics – a promise to help detecting the severity of Parkinson’s disease, and also translate the hand movements into speech. An MIT graduate student- an MIT – Tata fellow – is working in Mumbai towards developing ready to use therapeutic food to fight malnutrition in India. WHO is ready to start clinical trials for its malaria vaccine in three African countries. It might now be possible to think of growing premature human fetuses, of 23 weeks and above, outside wombs. If you are buzzing with an idea that can be translated, it might interest you to know that Millipore Sigma has joined hands with LabCentral, a nonprofit startup incubator in Massachusetts.

Despite these, hardships of traditional academicians haven’t changed much yet, with the indecisiveness of a postdoctoral tenure and the heavily unfavorable ratio of academic positions available with the number of applicants for tenure track. The first draft of Trump’s budget for this fiscal year is out, with sizable cuts in biomedical funding. The proposal claims that better planning will ensure achievements aren’t compromised. It has been a year since Germany announced plans to introduce 1000 tenure track positions in academia. University of Göttingen is trying to set an example by inviting suggestions from the current postdoctoral fellows in penning the proposal.

And finally let’s talk of the jobs available around –

  • Immunologists, take note of scientist positions at Biogen, Antibody Discovery, MA, NIBR Biologics Centre, MA, and multiple positions open at CSIR-IMTECH, Chandigarh in areas of therapeutic R&D and drug discovery
  • Electrophysiology experts might want to check the scientist position, at Synapses and Circuits, Roche, Basel, Switzerland
  • Check the exciting scope of ‘designing your own role’ at Chan Zuckerberg Biohub
  • In this age of CROs, know what are the skills that are sought for in a Clinical investigator, and see if the position of Clinical Trial Manager at Celgene suits you.
  • For those interested in advancing and revamping science education, check this interesting postdoctoral fellowship at Yale-NUS College, Singapore
  • Those interested in exploring industrial collaborations while being in academia, take a look at calls from Boehringer Ingelheim for research proposals around GPR68, and an industrial postdoctoral position at Biogen, MA to study neurodegeneration
  • Interested in working on RNA mediated gene regulation? Check the Research Associate position at Cambridge, UK
  • For the non-biologists wanting to transition into biomedicine, Francis Crick Institute is looking for group leader positions in physical sciences
  • For the psychologists among us, there is a lecturer position open at University of Reading, UK
  • For those imaging lovers with commendable interpersonal skills, see if the Microscopy Specialist position at PicoQuant, Berlin, Germany interests you
  • Those without a PhD and wanting to explore industry might want to consider the Scientific Assistant position at the Biorefinery department, Luxembourg Institute of Health

And if you are confused among what to choose from, do consider the possibilities of having multiple careers at once – there are many now who can vouch for its merits.

Nevertheless know the essentials of effective networking from the uber successful in the industry – Chris Fralic talks of his networking stories in the pre-LinkedIn era. And today with technology helping you in your pursuit, you really don’t have to wait for an opportunity to open up to express your will to work with someone – just cold email, the right way though. But at the same time, it has also become more common to have not-in-person interviews. Know how to ensure you make the best impressions on the telecommunication based interviews.

And when this gets too daunting and overwhelming, make sure you are getting enough of that sun. With the regular CSG meets happening all around, here is an interesting outdoorsy and nerdy enough an idea that you might want to consider. Happy May coming soon – we will ensure that you use the summer cheer to the fullest to grow personally and professionally!

About the author:

Somdatta Karak works with Club SciWri as a project co ordinator and Corporate Liaison. She is a doctorate in neuroscience from Georg August University, Göttingen, Germany and has been a Teach for India fellow (2014-16). She loves putting her analytical skills to build newer and more sustainable solutions, enjoys traveling and communicating and takes every opportunity to expand her horizon.

You can reach her here.

 

 

The Patent Chronicle

in Sci-IP by

Your weekly dose from the world of patents (April 4th, 2017). The Patent Chronicle is led by Syam Anand, who has been at the core of CSG’s development and an entrepreneur himself. This section is your go to destination every week for a capsule dose on the hottest happenings in the patent world. Syam has clinically dissected out every news on the decision, the background and the impact. He is also in the process of building his scicomm team for this section. If you would like to come aboard, mail him at syam.anand@sciwri.club.

EPO to give CRISPR rights to UCB

Decision: European Patent Office (EPO) indicated its intention to give a broad CRISPR patent to UCB.

Reason: EPO is convinced that UCB’s CRISPR application has been enabled for BOTH prokaryotes and eukaryotes.

Impact: UCB gains upper hand in Europe in the CRISPR battle. Broad can still file an opposition to the EPO decision. UCB could end up amending claims affecting the scope of the patent. This is more or less going to end up as in USPTO with UCB getting a broader patent and folks wanting to use CRISPR in Europe and US having to license from both, IF they use it in eukaryotes.

Read more here

 Troll paradise Marshall, Texas could get hit

Decision: Pending

Reason: Opposing precedents as to where a patent owner can initiate proceedings for infringement- one set says place of incorporation, the other says place of operations (however minimal it is). Patent owners and trolls have been flooding to Marshall, Texas (a town with 25,000 population) and case numbers in the town are around 34% of those filed nationwide.

Impact: Supreme court decision will direct which precedent is the law of the land. Trolls could lose on their strategy litigate in “friendly” jurisdictions.

Read more here

NIH funding cuts will impact patents and innovation

Decision: The Trump administration has proposed the following cuts to NIH budget- 1.6 billion USD for 2017 and 6 billion USD for 2018.

Reason: Divert funds to increased defense spending.

Impact: Study led by a Harvard Business School entrepreneurship professor shows that both basic and applied research contribute to commercial innovation. In one author’s own words “neither the progress of life sciences research nor its contribution to the economy is neat or easy to quantify”. “The sausage factory doesn’t look up-close very appetizing,”. “But in the sweep of history, this system delivers things.” 10 % of NIH grants resulted directly in a patent and 30% in articles were subsequently cited by patents. Innovation will take a hit as a result of the funding cut’s impact on both basic and applied research.

Read more in here and here

BMS Dasatinib patent dismissed for no utility

Decision: Federal court finds ability to inhibit an enzyme cannot to be extended to a utility to cure cancer without sufficient proof. It is an overarching promise and lacks utility.

Reason: Apotex wanted to sell Apo-dasatinib in Canada and was opposed by BMS. Apotex alleged inutility, obviousness and double patenting.

Impact: Apotex can sell its drug in Canada. Sets a precedent for questioning a patent’s utility and enablement without direct proof.

Read more here

Small Business Innovation Protection Act

Decision: U.S. Senators Gary Peters (D-MI) and Jim Risch (R-ID) have reintroduced the bill aimed to protect the IP of small businesses by improving education on patents prosecution and beyond.

Reason: Lack of awareness of international patent protection that affects small businesses ability to protect their inventions outside US, especially China and other major international markets.
Impact: More in person and online training and outreach programs from Small Business Administration and USPTO through Small Business Development Centers.

Read more here

 

Biogen wins MS drug Tecfidera dispute

Decision: USPTO’s Patent Trial and Appeal Board ruled that Forward Pharma failed to prove Biogen had infringed on its patent.

Reason: Insufficient scientific description for proving infringement.

Impact: Biogen does not have to pay royalty to Forward Pharma with this ruling. However, an appeal of PTAB decision by Forward Pharma in a court could reverse the fortunes. Biogen had earlier licensed the use of dimethyl fumerate (active ingredient of the drug) from Forward Pharma making this a self-inflicted wound in a court battle.

Read more here

 About the author:

Syam

Authored by Dr Syam Anand, PhD (Indian Institute of Science, IISc; Post-Doctoral research, University of Pittsburgh School of Medicine; Faculty, University of Pittsburgh School of Medicine, Founder and US Patent Agent, Mainline Intellectual Property LLC, Ardmore, Philadelphia USA). Syam has over 20 years experience in diverse areas of Science with domain knowledge in Life Sciences and Intellectual Property. Dr. Anand is also an inventor and budding entrepreneur. A rationalist, Dr. Anand enjoys science at all levels and advocates the use of scientific methods for answering all questions and solving all problems and make common people curious and interested in understanding their worlds.

https://www.linkedin.com/in/syamprasadanand

Featured Image source: Pixabay

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MedNess- March Mania

in Medness by

Hello and welcome to yet another exciting week of MedNess. In this March mania, we bring the news from medicine and healthcare with the greatest impact.

Tom Price justifies NIH’s “indirect” budget cuts

Secretary of Health and Human Services (HHS) defended Trump’s administration proposed National Institute of Health’s budget cuts. The Trump administration proposed $5.8 billion, about 18% cut for the fiscal year 2018. In addition to that, an addendum proposed an additional $1.2 billion cut for the current fiscal year. When questioned by both democrats and republicans about the nature of budget cuts, Price explained to reduce the “overhead” costs to streamline the system. According to the Secretary of HHS, the “indirect” cost takes up about 30% of the grant money, which could otherwise be available for research.
This came in as a second blow to the medical research community. Earlier this year, Trump administration pushed deregulation of FDA to accelerate the drug approval process. The research community did not welcome this proposal. Also, both pharmaceutical companies and insurance companies did not approve of the proposition (STAT and Science).

 

March for Science, a scientist’s view:  For our readers, “overhead” or “indirect” costs constitute of anything required for carrying out research safely, smoothly and efficiently! Some of the “indirect” costs include lab equipment, electricity, custodial services and other utilities. The list is not inclusive but clearly, emphasizes the importance of overhead charges. The budget cuts will not only affect the advancement of research but will also impact jobs and outreach of science. For non-science professionals, say, politicians, the overhead cost will include, electricity, custodial services, security, dinner, travel, etc. Again, the list is not inclusive! Of course, these expenses are required for the smooth functioning of the government. Before I wrap up the section, just a thought: yes, we need the stronger military to defend the country, but we need to ask this question, who are we protecting; the people and the Mother Nature. Therefore, we need an effective EPA and NIH. We need the healthy and clean environment and disease-free children and adults.

Amgen’s LDL-lowering drug Repatha: effective drug with good data for a bad price?
Amgen presented Phase III FOURIER results on Repatha (Evolocumab) at the 2017 American College of Cardiology conference. Repatha is an LDL-lowering PCSK9 inhibitor. Repatha targets PCSK9 proteins in the blood stream thus preventing it from binding to and breaking down LDL cholesterol receptors in the liver. The trial results were impressive. This wonder drug is believed to break down the most stubborn cholesterol. The FDA approved drug marketing in 2015 after the drug’s addition to statins reduced the LDL levels by about 63%. At the ACC, Amgen reported the outcome of long-term FOURIER trial and the results showed that Repatha reduced the risk of heart attack and stroke by 15% or more. Repatha met both its primary and secondary composite endpoint in the secondary prevention trial demonstrating superiority to statin therapy. However, analysts are not too impressed with the data and question the high price of the drug. Earlier, analysts with BioPharmInsight suggested that the high price of Repatha could be justified if the cardiovascular event risk reduction is at least 35%. Repatha has been price tagged for $14,000 annually. The trial findings and analyst’s reports will also affect insurance coverage of the drug (MedPage Today).

MedNess: PCSK9 is the hottest target in the field of cardiovascular research. While Amgen’s drug can crush the most stubborn cholesterol molecules, the investors were not impressed, or at least the stock market trend did not concede with it. After the results had been announced, Amgen’s stock price went down by 10%. However, a lot of analysts are still keeping their faith in Amgen’s stocks and considering this temporary dip as an opportunity for investment. On the contrary, the competition from other biosimilars is getting fiercer, and the dip in stock price might not be temporary after all. Other contenders in this area with Amgen, are the drugs from Sanofi and Regeneron. Both the companies are locked in a patent battle with Amgen. Another drug in the race is The Medicine’s Company’s inclisiran. Unlike Amgen’s, Sanofi’s and Regeneron’s drug, inclisiran interrupts PCSK9 synthesis. The analysts look at this drug as efficacious as Repatha but with fewer annual doses. If this assumption is correct, Amgen will have a hard time convincing insurance companies for their drug price. The best bet might be therefore to either wait or invest wisely (The Motley Fool and Seeking alpha).

FDA approves Roche MS drug Ocrevus after 3-month delay

The FDA approved Roche MS drug Ocrevus after initial delay caused by regulator’s concerns over manufacturing issues.
Ocrelizumab, becomes the first U.S.-approved medicine for the primary progressive multiple sclerosis. It has also been approved for relapsing-remitting multiple sclerosis (RRMS). Biogen’s MS drug has been used to treat RRMS. Biogen will receive up to 24% royalty on U.S. sales of Ocrevus. According to the pharmaceutical giant; Ocrevus is expected to be available for use to people within two weeks.

 

MedNess: Analysts forecast annual sales exceeding $3 billion by 2021 as reported by Reuters. After the approval news, Biogen stock fell by 2%, and Roche stock rose by a fraction. Novartis’s drug for MS treatment, BAF312, for secondary progressive MS is expected to receive regulatory approval in the first half of 2017. Until then, Roche can bask in glory  (Reuters, Investor’s Business Daily, FiercePharma).

FDA approves Tesaro Inc’s Niraparib for the treatment of Ovarian Cancer

Tesaro’s Niraprib (Zejula) gained an early approval by FDA for the treatment of recurrent ovarian cancer. Zejula is a PARP inhibitor causing DNA damage. It is a first drug in the class that can be used to treat all women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer without requiring BRCA mutation or biomarker evaluation. This is unlike the rival drug Lynparza by AstraZeneca. In addition, Zejula acquired orphan drug designation for its use in the treatment of recurrent epithelial ovarian cancer.

MedNess: According to EvaluatePharma, Zejula is one of the top drug launches of 2017 with 2022 sales expectations of $1.9 billion. Tesaro Inc’s shares were up 7.78 percent after the drug gained FDA approval (FiercePharma and BusinessInsider).

Illustration: Ipsa Jain

About the Author

Imit Kaur is a freelance medical writer, editor and an active science blogger. She pursued her PhD in Pharmaceutics and Pharmaceutical Chemistry from University of Utah. She is experienced in the field of oncology, hematology, pharmacology, nanotechnology and drug development.

The week that it was – 20th to 26th March, 2017

in ClubSciWri by
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CSG is now a platform with 6000+ members and CSG-Europe has started to bloom. Among the wide variety of information shared on the platform daily, I decided to bring you the opportunities to shape your future (of course, I know how you love to see them), help to deal with them and some refreshing foods for thought.

Time is ripe to attack the predatory science journals under the pretext of open access publishing, as researchers from Sussex carry out sting operation to expose 48 of them.

While Harvard Medical school scientists propose revising guidelines around genetic engineering, Nobel laureate Harold Varmus, Cornell Weill Medicine voices concerns around NIH budget cuts proposal.

Director of IISER Thiruvananthapuram, Prof. V. Ramakrishnan faces scrutiny for plagiarism; many academicians had objections to his appointment in the first place.

While CSIR lost enough of tax-payers money in filing non-revenue generating patents, researchers from IIT-Madras suggest possible solutions.

The market always loves and grooms the ones with exciting ideas –

  • Startup India brings free online extensive 4 weeks program for entrepreneurs to learn from the leading names in the country
  • Falling Walls lab, an initiative by German Centre for Research and Innovation, New York is looking forward to hear your research/ entrepreneurial idea to sponsor your meeting with other bright minds in Berlin, Germany
  • JoVE offers exciting prizes for filming equally exciting research work
  • And do not miss the opportunity to get connected with the pioneers in biotechnology in New York via the GRO BioPharma conference on 5th April

Illumina takes Next Generation Sequencing (NGS) techniques to fisheries; promises its help in increasing fishing yield.

Grab the openings-

With this mighty a list of openings, chances are high one of them interests you. Get started with the application then. Here are some tips on excelling your postdoc application, writing the perfect resume and cover letter. We don’t want to take chances here!

About the author:

Somdatta Karak works with Club SciWri as a project co ordinator and Corporate Liaison. She is a doctorate in neuroscience from Georg August University, Göttingen, Germany and has been a Teach for India fellow (2014-16). She loves putting her analytical skills to build newer and more sustainable solutions, enjoys traveling and communicating and takes every opportunity to expand her horizon.

You can reach her here.

 

 

MedNess-Pill for Alzheimer’s?

in ClubSciWri/SciBiz/Uncategorized by

Hello and welcome to yet another exciting week of MedNess. We bring the news from medicine and healthcare with greatest impact. It seems like; year 2017 will be the year of neurology! It is just the second month of the year and treatment strategies for various neurological disorders are making headlines.

Merck halts Phase 3 study on Alzheimer’s drug- another setback for amyloid theory

Clinical trials on Verubecestat- a small molecule BACE 1 and BACE2 inhibitor were called off after an interim analysis on Phase 2/3 studies did not show promising results. The analysis team concluded that there was “virtually no chance of finding a positive clinical effect”. However, another trial on patients with early symptoms of Alzheimer’s will continue. It has been speculated that the drug was too weak, or was dosed inadequately or the disease had progressed too far in patients for the drug to show concrete effect. The failure of this trial is another blow to the famous “amyloid theory”. According to this theory, the amyloid plaques are believed to be cause of the disease. Verubecestat is a beta secretase inhibitor. This disappointing cessation of clinical trial came months after Eli Lilly’s Alzheimer’s drug; Solanezumab failed in Phase 3 clinical trials in November last year. Unlike Verubecestat, Solanezumab targets plaque rather than beta secretase enzyme. This brings in disappointment not only for the patients but also for the researchers. The evidence suggests that once the disease has advanced and patients have established dementia, the removal of amyloid plaque might not yield effective outcome.

                              Do we have a pill to cure Alzheimer’s? Some quick facts:

  • Alzheimer’s is an irreversible brain disorder causing cognitive impairment
  • More than 5 million Americans are expected to suffer from Alzheimer’s
  • Sixth leading cause of death in the USA
  • No new drug has been introduced to provide symptomatic relief or to halt its progression since last decade

Picture source: https://unsplash.com/search/brain?photo=rmWtVQN5RzU

There are couple of drugs at various stages of trial that are being tested under the amyloid plaque hypothesis. These drugs either act on the plaque or beta secretase enzyme (BACE inhibitor) or available as amyloid immunotherapy. These candidate drugs are from Biogen, AstraZeneca, Eli Lilly, Amgen and Novartis. Apart from BACE inhibitors, hopes are also high for Axovant’s intepirdine. Intepirdine is believed to improve cognitive symptoms by targeting receptor 5-HT6 that stimulates the release of a neurotransmitter. Interestingly, intepirdine was abandoned by GSK in 2010. The drug failed when compared to placebo. However, one study showed tangible effect on cognitive symptom when intepirdine was paired with the approved Alzheimer’s drug Aricept.

MedNess: Merck’s stock suffered severe blow after the announcement of cessation of clinical trial. On the contrary, shares of Eli Lilly, AstraZeneca, Biogen and Roche, the fellow Alzheimer’s drug makers, increased. (Fierce Biotech, Business Insider, STAT news, The Boston Globe)

Axovant’s nelotanserin passes phase 2 study for Lewy body dementia

Axovant Sciences declared successful completion of phase 2 study of nelotanserin. The company is now setting its foot forward for phase 3 study that is expected to initiate later this year. Axovant Sciences reported preliminary results from the first small group of 11 patients.

Lewy body dementia or LBD is the second most common form of dementia. The hallmark characteristic of this form of dementia is the build up of abnormal proteins i.e. Lewy bodies thus affecting cognition, movement, behavior and alertness.

The study included patients with either LBD or Parkinson’s disease dementia. These patients experienced frequent hallucinations as assessed by mini mental state examination (Pharmaceutical Business Review)

CRISPR battle of patents: The Broad institute and MIT wins!

The scientists who first demonstrated the use of most powerful gene editing technology in biotech suffered a major blow on Wednesday, February 15, 2017, in their fight to gain exclusive rights on their invention. CRISPR gene editing system has revolutionized the field of biotechnology enabling scientists to make changes in DNA. Jennifer Doudna, a UC Berkely biochemist and her European collaborator Emmanuelle Charpentier first published this gene editing technology in prokaryotic system (type of bacterial system) in 2012 in Science. UC Berkely and University of Vienna filed for U.S. patent in March 2013. There were 155 broad claims to the CRISPR-Cas9 technology. Feng Zhang, a biologist at the Broad Institute, demonstrated the use of this technology in eukaryotic cells (type of plant cells, animal cells and human cells). The Broad Institute filed their patent in 2013; months after Berkeley group filed their patent. Since the patent claims by Broad Institute were fewer than Berkeley’s, the Broad Institute’s patent was issued on April 15 2014 through accelerated approval while Berkeley group is still awaiting their approval. After the Broad Institute was granted their patent, UC Berkeley filed an interference claiming that the Broad Institute should not have been granted the patent since Doudna’s and Charpentier’s CRISPR research outlined in 2012 paved the way for Zhang’s research in eukaryotic system. The Broad Institute argued that the research was not obvious and the patent claims from both the institutes were different. The federal Patent Trial and Appeal Board ruled out UC Berkeley’s claims and sided with the Broad Institute. With this decision, UC Berkeley plans to move forward with their patent application, which if approved, will provide them right on the use of CRISPR on all cells. This would also mean that if the technology will be employed commercially, the companies would have to get licenses from both the Broad and the Berkeley group.

MedNess: The patent decision in the favor of the Broad institute increased the stocks of Editas Medicine by 30%. Editas Medicine licenses Broad’s patents for human genetic disorders. (Fierce Biotech, STAT News, The LA Times, NPR, Wired)

Are pharmaceutical industries in favor of Trump’s FDA pick? The story so far….

Donald Trump is pushing deregulation of FDA in order to accelerate the drug approval process. His ideology: drug costs are higher, drug approval process through FDA takes forever, drug companies are involved in “unfair foreign trade”, drugs should be manufactured in the USA and finally, drug companies should add the innovation factor for the better cure of the diseases. This recipe will work in favor of patients to bring the overall drug costs down and patients can have quicker access to the newer agents. Not to forget, drug manufacturing in the USA brings back jobs and the “fair trade” promotes revenue generation. This all sounds good, except, the pharmaceutical industries have opposing views. The most common complaint of every patient and every healthcare researcher is the never-ending drug approval process by the FDA. So suddenly, when we might be able to overcome this hurdle, why is everyone (read the researchers, pharmaceutical companies and informed patients) so anxious? The truth is bitter sweet. Even though we rant over the FDA, we still knew, the FDA has best interests at heart and such a tight screen is probably important for the safety of the patients. In addition, a 2011, study found that the FDA usually approves cancer drugs before Europe does. Moreover, the researchers at Yale found the FDA’s drug review is at least a month faster than Europe’s or Canada’s.

The pharmaceutical industries on the other hand are concerned about the high drug costs. In addition to the limited patient safety, deregulation in the FDA might not provide enough time for pharmaceutical companies to justify high costs of the drugs to patients and to insurance companies. The pharmaceutical companies will not be able to account for high costs of the drugs owing the limited safety and efficacy analysis that ultimately affects both the patients and the companies. President Trump said last month he has a “fantastic person” lined up for the role of the FDA commissioner. A survey conducted by Mizuho Securities of drug company executives indicated that 72 percent agreed Scot Gottlieb should be Trump’s pick to head the FDA. Until then, we all wait! (Reuters, The New York Times, Forbes)

 

              

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