Super Agers Cognitive Process


Brain mysteries of SuperAgers by Amina Shakrullah

A new study has identified an elite group of elderly people who are 80 years old or above. These elderly people are having memory as sharp as the people 20 -30 years younger than them. Emily Rogalski, a researcher of the Northwestern University Feinberg School of Medicine, identified the elderly people who are still having a terrific memory. He called these people “SuperAger” because they have a brain that is decades younger than those of their fellow brains. The 3-D MRI scans; of the SuperAger participants revealed that one region of the brain was even bigger than the brain of the middle aged participants. Emily Rogalski was overwhelmed by the energy of the cortex of SuperAgers. The cortex is the outer layer of the brain that is crucial for memory, attention and other thinking processes of a person. The cortex of SuperAgers is much thicker than that of their fellow participants. Rather the size of their cortex resembles to the size of middle aged participants. In this study the middle aged participants were 50-65 years old.

According to Rogalski these findings are surprising as the grey matter or brain cells are lost normally during the aging process. She is the main investigator of the research, senior author of the paper published in the Journal of the International Neuropsychological Society and a professor at the Cognitive Neurology and Alzheimer’s disease Center. According to her SuperAgers are uniquely protected from the deterioration of memory and putrefaction of brain cells that leads to aging. With the identification of these SuperAgers Rogalski is hopeful to discover the secrets of their young brains. Afterwards these discoveries can be applied to the others to protect them from dementia and Alzheimer’s.

By studying the healthy older brains it is possible to infer how SuperAgers have maintained a good memory. The identification of the unique processes in the brain of SuperAgers will ultimately help the patients who are living with Alzheimer’s. By deducing and concluding all the information obtained from the healthy brains, the strategies for the treatment of Alzheimer’s can be improved. By observing the thickness of the cortex the number of neurons can be calculated. But the cortex thickness provides an indirect way of measuring brain’s health, as the thickness of the cortex is directly proportional to the number of neuron cells.

The difference in the SuperAgers’ brain and that of middle aged lies in another region of the brain. In the brain of SuperAgers the interior cingulated region is thicker. Roglaski said thickness of this part of brain is pretty incredible, because this region is crucial for attention. The memory is supported by attention and possibly SuperAgers possess keen attention helpful to support their exceptional memory. Only 10 percent people, who consider that they have an extraordinary memory, were able to fulfill the criteria of the research. To be called as SuperAgers the participants have to score greater in memory screening than the middle aged participants.

According to Rogalski these are special people who are rare. She viewed the MRI scans of 12 SuperAger participants from Chicago and screens their memories along with their cognitive abilities. During the research she also studied 10 normally aging people with an average age of 83.1 years. There were 14 participants from the category of middle aged with an average age of 57.9 years. Now, the SuperAger participants are willing to donate their brains for the research. Rogalski said that by looking into the brains of these SuperAgers the attributes of living persons with the underlying cellular features can be linked.

-Amina

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Court Ruling on Gene Patents


Myriad Genetics can patent human genes by Amina Shakrullah

The U.S. court has asserted again strongly its previous ruling that a biotechnology industry can patent isolated human genes. It’s a 2-1 victory for Myriad Genetic Inc, in a decision on 16th August court support the company to patent two genes BRCA1 and BRCA2. These two genes are associated with breast cancer and ovarian cancer so can signal the risk these cancers in women.  After this decision the company, which is situated in Salt Lake City, will become the exclusive commercial facilitator in the U.S. to provide diagnostic tests for the hereditary diseases. Where the courts’ decision is a success for Myriad Genetics Inc at the same time it’s a blow to the critics who thought and claim that patents are a hurdle for the practice of medicine.

According to the Daniel B. Ravicher human genes are neither genetic tools nor drugs that can be patented because they are synthesized. He also said it is wildly unreasonable that a company claims to own naturally occurring human genes just because they isolated them from the body. Daniel B. Ravicher is an executive director of PPF (Public Patent foundation). In response to the statement Myriad argued that when genetic material is extracted from the body is eligible to be patented as it is when it is removed it does not remain the natural product.

The court agreed with the claim of Myriads Inc that after the removal of DNA from body it becomes a new chemical that have considerable utilities. The company conducts a test known as BRAC analysis or Myriad’s gene test. The women which have a positive test of Myriad’s gene test have 82% greater risk of breast cancer and 44% increased risk for ovarian cancer. According to a trade association the Biotechnology Industry Organization the ruling against the patenting gene can have a ruinous effect on the future innovations. As the ruling against gene patenting will discourage the investors to invest in expensive and long research being carried at the U.S. Biotech companies and universities.

-Amina

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Google Earth for Cell Biologists


Virtual nanoscopy for biologists: a Google Earth by Amina Shakrullah

Google earth has become a big inspiration for cell biologists. Advancement in microscope technology aided researchers for the visualization of biological tissues. Zooming in and out of biological tissue can be done in a similar manner as you are using Google Earth. The advance microscopes with the resolution up to nanometers helped the researchers to reveal a great deal of knowledge about biological tissues. It is a well-known fact that the present microscopic technologies have some limitations. In a single snapshot, a small chunk of the biological specimen (cell or tissue) can only be visualized. So, because of this limitation the biologist cannot relate different parts of a cell and whole organism together.

Virtual nanoscopy, a new visualization technology developed by the researchers from the Leiden University Medical Centre Netherlands.The new approach shall help the researcher by displaying a small view in a single image. So, it enables biologists to draw a relation of a cell part not only to the whole cell and but also with whole organism. For generating full ultra-structure map of zebra fish’s embryo researchers stitched almost 26,000 images together. A large scale microscope is wondrous with a resolution of 16 million pixels per inch having 281 gigapixels.

According to Raimond Ravelli, this extraordinary technique will change the whole scenario. Instead of just getting a snapshot of a chunk of cell we shall be getting the whole cross section. He is among the author of the study that is published JCB. Collecting an entire section will enable us to a better understanding of the biological specimen. He also said that we are hopeful that advancement in the technology will revolutionize the analysis of biological specimen that will help in better disease diagnosis. With the development of faster detectors and automated segmentation strategies will give 3D analysis of cell and tissue with a high resolution.

It is just like Google Earth, where you can explore the whole world, countries and even streets, now with the help of virtual nanoscopy enables cell biologists to navigate biological specimens from complete organism down to the sub cellular structures. JCB DataViewer program provides access to public to explore the images of Zebra fish. It was launched in 2008. According to the JCB executive editor purpose of launching the program is to share original data.

-Amina

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Need for Biotechnology Education


Biotechnology: an Educationist Perspective by Sundus Mehmood

The two F’s of Science – “Fun” and “Fascination”, if taken out of Science, be it Biotechnology, Biology, Physics, Chemistry or any other Science, would be like taking sugar out of juice or serving a plain piece of bread with no butter or jam. If you don’t have anything to go with bread, would you eat it? Probably not! Likewise, if you are not fascinated about the wonders of Science and are not having fun studying it, you won’t study it!

Most students find it hard to develop interest in Science owing to the fact that it is based on factual knowledge and there’s nothing that you could “do” in it. While this is absolutely wrong, it is the responsibility, directly or indirectly, of the Science teacher, to engage students in hands-on practice. Science is best learned by “doing” and studies on learning, meta-cognition, etc have proved this.

Research studies found strong evidence that labwork enhances students’ interest and they analysed interest in labwork as a multidimensional construct (Ben-Zvi, Hofstein, Samuel, & Kempa, 1977; Hofstein, 2004; Hofstein et al., 1976, as cited in Glowinski & Bayrhuber, 2011). Several studies describe the motivating effects of situated learning in authentic contexts (Goldman, Mayfield-Stewart, Bateman, & Pellegrino, 1998, as cited in Glowinski & Bayrhuber, 2011) whereas it is noteworthy that there is no consensus on the definition of authentic science tasks (see review by Buxton (2006)) and there are many ways of implementing them in the science classroom. Some approaches focus on the adoption of scientists’ practices in order to help students learn scientists’ attitudes, and how to work with their tools and techniques (Edelson, Gordin, & Pea, 1999, as cited in Glowinski & Bayrhuber, 2011). Other approaches make use of everyday problems to develop students’ attitudes relevant for lifelong learning (Edelson, 1998; Lee and Songer, 2003, as cited in Glowinski & Bayrhuber, 2011).

No matter what teaching method the teacher employs, be it incorporating technology in the classroom, using 3D models or simulations, taking a trip somewhere, doing labwork, having demonstrations, solving puzzles, doing group activities with the students, etc, the idea is that the students are fascinated by Science, by the advanced technology that is available, by everything that is at the students’ disposal that was not a few years back and especially by what Science allows us to do today that we could not have even dreamt of a few decades back. Speaking of the wonders of Science, it would be a sin to not talk of Biotechnology and all the amazing things that it allows us to do now, be it production of better crops, production of products on a large industrial scale, gene therapy, etc.

But in Pakistan today, Biotechnology is an alien to many, despite the fact that every year an increasing number of students are opting for it for their Undergraduate and Graduate studies. A huge part of even the educated population is unaware of the “wonders of Biotechnology”. So what could be done to change this? Start bottom-up, i.e. if we want our students to take interest in this field and appreciate its wonders, we need to start working from the grassroot level – Secondary Education. Yes! We need to teach or at least introduce Biotechnology as a field of study as part of our Secondary Science curricula, the fun way! When teachers will teach Biotechnology the fun way, when they’ll let students do things in the laboratory (as long as no one gets hurt), when they’ll show students informative videos, when they’ll talk to them about latest and interesting research findings, in short, when they’ll employ a variety of teaching methods to teach Biotechnology to students while they are still in school, students would definitely be inquisitive about it, they would want to know more and explore possible areas of research in Biotechnology, more students would be interested to study it and pursue their careers in this field and who ultimately gets the benefit? We do! We will have products commercialized, we will have a lot of research going on – we will progress!

References

Glowinski, I., & Bayrhuber, H. (2011). Student labs on a university campus as a type of out-of-school learning environment: Assessing the potential to promote students’ interest in science. International Journal of Environmental & Science Education, 6(4), 371-392.

-Sundus

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Gene Therapy Approval by EMA


European Regulators okay first gene therapy drug by Amina Shakrullah

Almost 20 years ago the first experiment to repair the faulty genes was carried out. The experiment was a breakthrough in the field of drug discovery. Since that time scientists and drug companies are working hard for the practical application of gene therapy. Now, the approval has been given by the European regulators, to the first gene therapy drug of the western world. The approval of the gene therapy drug by European Medicines Agency (EMA) is a big achievement for the drug discoverers of uniQure, a Dutch Biotech company. This gene therapy drug is a potential lifeline for the patients suffering from an ultra-rare genetic disorder lipoprotein lipase deficiency LPLD.

However, it is too late for the investors of Amsterdam Molecular Therapeutics (AMT) a previously listed firm. Since the rejection of Glybera medicine by AMT and because AMT cannot support itself financially, AMT was taken private by uniQure in April. Two largest shareholders of uniQure are Forbion Capital Partners and Gilde Healthcare. Both companies are the leading life sciences venture capital companies in the Netherlands.

Patients suffering from LPLD have lost the ability to handle fat particles in their blood plasma. These patients hesitate from taking a regular meal as it results in acute inflammation of the pancreas. The LPLD disorder may lead to acute pancreatitis and even death. It is also estimated that the disorder does not affect more than one or two persons in a million. So, it was quite challenging to win the approval for Glybera the first gene therapy drug against LPLD. Because of the rare occurrence of the disorder company got just 27 patients for clinical trials. Initially, the European agency has been hesitant to approve the drug just because of the thin number of evidences. According to a London based watchdog the drug is accepted for approval because there are sufficient numbers of evidence to give a green signal for the approval of drugs to treat the worst affected patients.

The chief executive of uniQure said in an interview, it is only difficult to get the first approval either from EMA or FDA but we have achieved this goal. This approval will help to unlock the potential of gene therapy. The idea of disease treatment by the replacement of a defective gene with a working copy of that gene got its credibility in 1990. As in 1990 the first successful clinical trial for first gene therapy was carried out against a rare disorder, Severe combined immunodeficiency SCID. The disease is also known as “bubble boy disease” and patients suffering from the disease have a defective immune system so they cannot survive with the infection and most of them die in their childhood.

In 1999 an Arizona teenager died during a gene therapy experiment and in 2002 two French boys suffering from SCID developed leukemia. These two events were the major setback in the field of gene therapy. In 2003 Shenzhen SiBiono Gene Tech a china based company got the approval for a gene therapy drug against head and neck cancer. Until now, no product has been approved in Europe or United States. Recently, some world’s leading pharmaceutical companies are also exploring gene therapy. For example, GlaxoSmithKline has signed a deal with Italian researchers in 2010 for the development of a therapy against SCID.

The acting chairman of the EMA’s committee for medicinal products for human use said, the evaluation of the first gene therapy drug Glybera was not an easy task. He said that experts have decided to recommend the drug only to the patients which have the greatest need for treatment. The uniQure company is also looking forward to get the regulatory approval for Glybera in other markets like the United States and Canada.

-Amina

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RNAi Nanoparticles for Ovarian Tumors


RNAi nano-particles eliminating mice ovarian tumors by Amina Shakrullah

Researchers found RNAi nanoparticles eliminating tumors in mice suffering from ovarian tumors. The sequencing of the cancer cell genome revealed that in a cancer cell several genes are mutated, deleted or copied. For researchers who are looking forward for new drug targets, this treasure trove is a boon. But in a timely fashion to test them all is near to impossible. To speed up the process, of rapid screening of new drug targets in mice, researchers from MIT developed RNA nanoparticles delivering system. The first study conducted in mouse revealed that nanoparticles targeting ID4 protein can eliminate ovarian tumors. This study was carried out at Dana-Farber Cancer Institute and the Board Institute.

According to Sangeeta Bhatia, this nanoparticles system shall relieve a significant impediment in cancer drug development. Sangeeta Bhatia is a Professor of Health Sciences and technology, also a member of the David H. Koch Institute for Integrative Cancer research at MIT. She is among the senior authors of this paper. Bhatia also said that the research is an initiative to pipeline all the targets that are generated by genomics. Subsequently, all these targets will be filtered out by using mouse models and the important ones will be figured out. This shall help to prioritize the targets that are to be focused clinically by using RNA interference.

The cancer genome sequencing project by National Cancer Institute is pouring out a large data about the drug targets. Another project named as Achilles is trying to identify new promising targets for cancer drugs. The leader of Achilles project is William Hahn, director of the Center for Cancer Genome Discover at Dana-Farber. He is an associate professor of medicine at Harvard Medical School. He said among the available potential targets several are considered undruggable. Undruggable targets are those proteins that do not have any binding site for a traditional drug. The discovery of these nanoparticles, that  deliver a short RNA molecule have ability to switch off a particular gene, can be helpful for scientists to figure out undruggable proteins. Hahn also said if somehow we can find out how all this work in humans, it will open up a new class of targets that had not been available previously.

Abundance of targets:

Hahn and his co-workers are trying to figure out many genes whose functions had disrupted in ovarian cancer cells, through Project Achilles.  Furthermore this approach has helped a lot to narrow down the list of potential targets, by pointing genes that are critical for survival of cancer cells. Subsequently, the next step during the identification of a good drug target would be the development of a mouse strain through genetic engineering. The mouse strain would be missing a particular gene and the response of the mouse strain will note down after the development of tumor. Normally this method to study the function of the gene might take 2-4 years, but a much more rapid way is simply to turn off the gene after the appearance of tumors. For turning off the genes RNA interference (RNAi) offers a promising way. RNAi occurs naturally in the body, during this phenomenon short RNA strands bind to mRNA. After binding of short RNA strand the mRNA molecules are degraded and corresponding proteins never formed.

Since the discovery of RNAi, researchers have been pursuing it as a cancer therapy. But with this therapy, scientist encountered a trouble in safe and effective targeting as well as in the penetration of RNA into the tumor. Bhatia’s lab, have been working on RNAi delivery for several years, is now working in collaboration with Hahn’s group for identifying testing new drug targets. They are trying to develop a “mix and dose” technique. In this technique the scientists will mix up RNA delivery particles then inject them into the mice and will observe what happen.

Shrinking of tumors:

At first place, the researchers focused on ID4 protein. The protein is over expressed in ovarian cancer, the most aggressive kind of cancer, but absent in other types of cancers. The gene that encodes a transcription factor, thought to be involved in embryonic development. The particular gene shuts down in early life but somehow reactivates in ovarian cancer. For targeting ID4, a new type of RNA delivering nanoparticle was designed by Bhatia and her students. The newly designed particles do not only have the ability to target but can also easily penetrate the tumors; it is something that had not yet been achieved with RNAi. The particles are coated with a short fragment of surface protein that guides them to enter the tumor cells. These short fragments also led to a protein p32 that is found inside tumor cells. Erkki Ruoslahti, a professor at Sanford Burnham Medical Research Institute discovered this and many related fragments.

The strands of RNA are mixed with a protein inside the nanoparticles; the proteins guide them during their journey. After entering the cell the proteins are encapsulated by membranes called as endosomes. The Protein and RNA mixture, inside the endosomes, have ability to cross the endosomal membrane barrier to get into the inner compartment of cell to start breaking down of mRNA. When they apply these RNAi nanoparticles to mice suffering from ovarian cancer, these help in eliminating tumors.

Now, researchers are testing other potential targets of ovarian cancer as well as for other cancer types such as pancreatic cancer by using these particles. They are trying to develop ID4 targeting particles to treat ovarian cancer.

-Amina

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Investing in Pharmaceuticals


Investing in Pharmaceuticals by Zainab Ali

Global biotech merger volume has reached levels not seen in four years as big pharmaceutical companies pursue deals to get access to new drugs, with bankers saying therapeutic areas such as cancer, inflammation and autoimmune diseases are proving to be especially attractive.

According to the healthcare bankers at Credit Suisse Group, large pharmaceutical firms with their expired patents eying for products to complement their drug development power and also give their prime-care sales power more drugs to sell.

Charles Newton, head of biotechnology investment banking at Credit Suisse, told in an interview, “There appears as there is a lot of interest in selected oncology names, inflammatory as well as autoimmune spaces.” He said, these were the main therapeutic areas where big pharma business expansion teams are likely to spend a lot a time. However, it is difficult generalize all over the industry.”

One of the worst patent overhangs is being faced by big drug making companies. They have an easy they are flushed with case and even have an easy access to debt which allows them to make heavy bids for capable biotech companies and various other targets.

According to Thomas Reuters data of Thursday, so far this year the volume of Biotech and M&A have been compelled to more than $25 billion, compared with the last year’s that was nearly $10 billion in the same time period. The data shows that the volume is highest since 2008, when deal volumes rushed to $54 billion due to Roche‘s (ROG.VX) $46.7 billion takeover of Genentech.

Scott Lindsay, global head of mergers and acquisitions at Credit Suisse said, “Their patents have been expired, due to this they have holes in their revenue line they are trying to fill. Rest is shoring up the pipeline they have. So even if they do not have a patent problem they are still looking for growth.”

The data shows that Credit Suisse’s healthcare team advised on $16 billion of this year’s biotech deals managed taking the top spot in the global rankings of deal advisers in the sector.

Recently the bank counseled Human Genome Sciences (HGSI.O) on its $3 billion sale to GlaxoSmithKline Plc (GSK.L), and Amylin Pharmaceuticals Inc (AMLN.O) on its $5.3 billion sale to Bristol-Myers Squibb Co (BMY.N). Inhibitex was also advised by Credit Suisse on its $2.5 billion takeover by Bristol.

The past numerous months have seen a vigorous takeover desire for hepatitis C drugmakers i.e. Inhibitex, and saw Pharmasset’s near $11 billion sale to Gilead Sciences Inc (GILD.O). Many other bidders’ were towed to the auction process underlining the interest of makers of hepatitis C drugs by both, Pharmasset and Inhibitex.

Often competition for these assets leads to buyers paying heavy payments.

101% premium to the price was paid by Bristol-Myers to Amylin before the interest was first reported. Bristol also paid a heavy amount of 163% premium to Inhibitex. GSK’s $3 billion annexation was a 99 percent premium to Human Genome’s stock before its bid was made public for the first time.

The three highest premiums paid for multibillion-dollar M&A transactions in the history of the biotech industry are Inhibitex, Amylin and Human Genome Sciences, said Newton. He also added that, “it might be thought whether targets are getting too expensive because of these premiums but we do not believe that people entirely through the lens as the premium paid is only one variable in the equation.”

Big pharmaceutical companies prefer commercial stage assets rather than clinical trial stage drugs that go through regulatory approval risks. This clearly shows that companies tend to chase multibillion-dollar transactions rather than going for smaller deals.

Lindsay said, “The scale of large pharmaceutical companies becomes a factor at much higher numbers than it would in other industries.”

-Zainab

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