Science & Enterprise subscription

Please share Science & Enterprise

RSS
Follow by Email
Facebook
Facebook
Google+
Twitter
Visit Us
LinkedIn

Affiliations

Science Blogs
ACI Profile for Alan Kotok
Featured in Alltop

Start-Up to Offer Neuro Disorder Speech Analytics App

Nerve cells illustration

(commonfund.nih.gov)

27 June 2017. A start-up enterprise in Germany is commercializing a software app to detect early signs of cognitive decline, found in dementia and other neurodegenerative disorders. The company ki elements — the name is spelled in all lower case — in Saarbrücken, Germany is a spin-off business from EIT Digital, a technology and entrepreneurship education organization in Brussels, Belgium.

Earlier this year, EIT Digital began work on its Element program to develop an app that analyzes speech patterns to assess neurological and psychological factors in individuals linked to cognitive decline. The program seeks to make diagnosing neurodegenerative disorders, such as dementia, easier, faster and less intimidating for individuals. Detecting these signs earlier can open more treatment options to individuals and maintain their quality of life. The system’s developers estimate only about half of dementia cases in Europe are diagnosed, which has significant implications for health care systems and care delivery networks.

Alzheimer’s Association International says some 47 million people are living with dementia, and that number is expected to rise to more than 131 million by 2050. In its 2016 annual report, the group says Alzheimer’s care is over-specialized, meaning too many neurologists, psychiatrists, and gerontologists are providing routine care. With the expected sharp rise in dementia cases, the number of these highly-trained specialists cannot keep pace, which will likely require different skills and solutions for tasks such as diagnostics.

The Element program is harnessing computation linguistics for an app that can screen individuals in their homes or care facilities for signs of cognitive decline by analyzing their speech patterns. DFKI GmbH, the German Research Center for Artificial Intelligence, is developing the initial app algorithms and software. Inria, the French National Institute for computer science and applied mathematics, is collecting the language texts for analysis, as well as conducting video analyses and arranging clinical trials.

The Element app is expected to be introduced first in French and German-speaking regions. However, University of Edinburgh in Scotland is adapting the program to British English speakers. While the software is designed for use by clinicians, it is expected to be used widely in home care and institutional settings by medical professionals, but also by non-medical professionals, such as speech therapists. An alpha version of the software is completed, which ki elements is expected to take into clinical trials, regulatory reviews, and the marketplace.

Jan Alexandersson, CEO of ki elements, says in an EIT Digital statement, “The company is set up and fully operational. The next steps for us is that we are now working on a fully functional prototype so we can start engaging with our first customers by end of 2017 or beginning of 2018.”

He adds that, “We are also working on CE certification [regulatory approval in Europe] of our product and looking to extending our portfolio towards the German market by the end of 2018. For 2017, our focus is on the French market.”

More from Science & Enterprise:

*     *     *

Understanding What Works: Why It’s Beneficial To Get Inside The Mind Of The Consumer

– Contributed content –

27 June 2017. When you’re trying to establish a successful business, there are few things that will benefit you more than understanding what consumers want and how they think. If you can get inside the mind of your customers, you can increase your chances of being able to give them what they want, and ultimately, generate more profit. If you run a business, and you’re keen to maximize your income and ensure your customers enjoy a positive experience, here are some hacks to help you understand what works.

Consumer's mind

(Christopher Dombres, Flickr)

Market research

It’s incredibly important to understand your market when it comes to setting up a new business or trying to keep an existing company afloat. If you go into something all guns blazing without doing your homework first, there’s a high risk of failure. Before you develop new products, change the way you operate or set new pricing guidelines, get some reaction and feedback from potential customers first. The information they provide you with can be so valuable. You should have in-depth knowledge of who your customer is, what they want, how they shop and how much they want to pay for your products or services.

There are many different ways you can conduct market research from traditional techniques such as paper questionnaires to email surveys, comment boxes, and interactive chat features. You may find that if you’ve used a live chat feature, you’ve been asked to rate the service and share any ideas afterwards, for example. This could be an option worth considering if you don’t already use this method. If users tell you that they’d rather use live chat than make a phone call to a helpline or they’d spend more if you offered free delivery, for example, comments like this can help you improve your business, and ensure that your company is more customer-focused.

(Merhad77, Wikimedia Commons)

Connecting with your customer

As a business owner, you should always show an interest in connecting with your customer, whether this means engaging in face to face contact or providing them with options that enable them to get in touch with you via telephone or through your website. If you have a basic website, which doesn’t offer interactive features, it’s worth looking into improvements you can make. If you’re keen to be more clued up about site design or you’re eager for your employees to develop additional skills, it’s worth investigating courses like javascript classes by Training Connection. By pursuing advanced training, you’ll gain an understanding of the benefits of additions like slideshows and video clips, as well as learning how to include these features on your site. It’s always beneficial to offer your customers more. If you run an online clothes store, for example, giving clients the option to watch a slideshow, such as a catwalk featuring items they may buy, and ask questions and get an instant response, will work in your favor.

Once you’ve made contact with customers, don’t assume that they’ll come back. It’s important to maintain relationships and to encourage that client to choose your business again. Send out offers in the post, connect via social media, or offer promotions via email for subscribers.

Email on phone

(Gerd Altmann, Pixabay)

Analyzing trends and habits

There are lots of patterns and trends when it comes to how people shop and what they buy. It’s also incredibly useful to see how effective different types of marketing and advertising are, as this can help you streamline your strategy and tap into methods, which have proven successful for competitors. If you notice that a lot of people are engaging with you via sites like Facebook, for example, and this is increasing traffic to your website, it may be worth investing more money in advertising on Facebook and cutting back on other platforms, which aren’t generating much interest. On a wider scale, you can also use analytics to determine what consumers are searching for online, and what appeals to them most in terms of marketing offers. Is a flash sale more appealing than a voucher that is valid for a month? Is a 3 for 2 deal more alluring than 20% off a single purchase? It’s worth investigating what people do to adapt your business to suit the modern-day consumer. As patterns and trends constantly change, being on the ball can help you keep hold of existing customers and attract new ones.

Analytics illustration

(Tumisu, Pixabay)

Business is not just about developing the best products or offering services that people need. It’s also about understanding what your customers want. It’s important to consider your market at every stage and to take steps to get inside the mind of the consumer and tailor your approach to suit the client.

*     *     *

Nanoparticles Built to Detect, Measure Peanut Allergy

Peanuts

(National Institute of Food and Agriculture, USDA)

27 June 2017. A chemical engineering team developed a system with nanoscale particles to better detect and diagnose the severity of peanut allergies. Researchers from University of Notre Dame in South Bend, Indiana describe their technology in the 21 June issue of the journal Scientific Reports.

Allergies to peanuts and other foods are a result of the body’s immune system misinterpreting certain foods as pathogens, and responding by the release of histamines, chemicals in the body causing the allergy symptoms. In most cases, the symptoms are mild, such as runny nose and itching, but people with peanut allergies face a real and elevated risk of anaphylaxis, a life-threatening condition constricting airways, swelling the throat, and causing a sharp drop in blood pressure. Food Allergy Research and Education says some 15 million people in the U.S. and 17 million people in Europe have a food allergy, with growing numbers of people reporting an allergy.

Researchers from the chemical engineering lab of Basar Bilgicer at Notre Dame are seeking better tools to diagnose peanut allergies, particularly the severity of the condition. Current diagnostics like the skin-prick test use allergens to stimulate a controlled immune response, while other tests like oral food challenges ask individuals to eat increasing amounts of the suspected allergens until reactions occur. Both types of tests run risks of discomfort, and in the case of the oral food challenge, severe responses leading to anaphylactic shock. While the tests may detect allergies, they provide little data on the severity of the allergies, and many parents are uncomfortable about exposing their children to their associated risks.

Bilgicer and colleagues designed techniques to detect peanut allergies, but also determine their severity, from blood samples. The researchers use nanoscale particles — 1 nanometer equals 1 billionth of a meter — called nanoallergens that resemble the 8 key epitopes, or binding regions of a leading allergen affecting some 90 percent of individuals with life-threatening peanut allergies. These binding regions are the targets of antibodies in the immune system that cause the allergic reactions. The nanoparticles are made from lipids, or natural oils, configured into round sacs called liposomes, with peptides representing the different epitopes on their surface.

The team tested the nanoallergens with serum, the component in blood containing immune systems cells, from an individual with a peanut allergy. An immunology test called Elisa, short for enzyme-linked immunosorbent assay, identified the specific epitope on the immune system cells, which were verified with nanoallergens expressing the same epitope.

The researchers then used the nanoallergens to measure the severity of the allergy, again with serum samples from a person with a peanut allergy. The team measured enzymes released during allergic reactions when immune system cells respond to allergens, then associated the specific enzymes to the individual epitopes on the nanoallergens. The results show the nanoallergen system can measure the severity of immune system reactions by the quantity of enzymes released, as well as highlight the individual epitopes in the allergic reaction, giving a more detailed profile of the allergy.

Bilgicer takes part in Advanced Diagnostics and Therapeutics, a university initiative investigating a range of health-related technologies, leading to a number of spin-off enterprises. He plans to advance the nanoallergen technology further with larger samples of allergy patients and extend it to related allergies. “We are currently working with allergy specialist clinicians for further testing and verification of the diagnostic tool using a larger patient population,” says  Bilgicer in a university statement. “Ultimately, our vision is to take this technology and make it available to all people who suffer from food allergies.”

More from Science & Enterprise:

*     *     *

Noninvasive Prenatal Testing is a Safe Way to Screen for Genetic Abnormalities

– Contributed content –

Pregnant woman

(Greyerbaby, Pixabay)

26 June 2017. Noninvasive prenatal testing is a way for parents to screen their unborn child for a variety of chromosomal anomalies. In the past screening an unborn child for genetic abnormalities was a much more dangerous process since it required the extraction of amniotic fluid from the protective sac that the unborn child is in. Anytime you use an invasive procedure such as Amniocentesis there are going to be risks involved. Still many parents would choose to have this test done if they were considered to be high risk for having a child with genetic abnormalities. Some people may question the ethics involved in screening for genetic abnormalities which may lead parents to choose to terminate the pregnancy. However, when you consider the quality of life that a child with severe genetic abnormalities may have, then the prospect should seem much more reasonable to most people.

How noninvasive prenatal testing is done

Unlike the more risky Amniocentesis noninvasive prenatal testing doesn’t involve disrupting the delicate sac surrounding the baby. Instead a small blood sample is taken that contains both the mother’s blood and the unborn child’s blood. Once the sample is taken it is sent to a lab where they use a cell free DNA extraction kit to recover genetic material from the blood, which can then be screened for various genetic anomalies. If a woman is interested in having this type of noninvasive prenatal testing done then she should discuss it with her doctor and set up the screening once they are at least 10 weeks pregnant.

Once the blood sample is taken results are usually available about 2 weeks later, at which point the parents will be informed if there were any problems detected.

The biggest advantage of this type of prenatal testing is of course the safety of both mother and child. In the more invasive amniocentesis there are many risks involved that could prove to be very problematic. These risks include inducing early labor, damaging the fetus with the needle that is used to extract the amniotic fluid, causing respiratory issues for the unborn child, and also the risk of Rehsus disease for the mother. On top of those risks there is also the issue of having to use a local anesthetic since inserting a needle deep into the body of the mother and be quite painful.

What genetic abnormalities does noninvasive prenatal testing screen for?

  1. Down Syndrome
  2. Trisomy 18
  3. Trisomy 13
  4. Trisomy 16
  5. Trisomy 22
  6. Triploidy

While noninvasive prenatal testing is not as thorough as amniocentesis, it is also a much safer option. There is literally no risk to the mother or unborn child making this type of testing something that every set of parents should consider. If a woman is interested in having this type of testing done then she should speak to her doctor and have the test scheduled once she has reached a minimum of 10 weeks into her pregnancy.

What are some of the reasons that someone would opt to have noninvasive prenatal testing?

While anyone can elect to have noninvasive prenatal screening done it is especially important for parents that are at a higher risk of having a child with genetic abnormalities. For example if a couple has already had a child with Down Syndrome or any other type of genetic abnormalities then the parents should definitely have this screening done. Another risk factor involves having a mother that is older than normal child bearing years since the chances of a problem will be quite a bit higher than they would be for a younger mother. Another major risk factor is if the mother has Rh negative blood and her child has Rh positive blood this could result in antibodies being produced that could prove to be problematic.

Is noninvasive prenatal testing the right choice for me?

In the past invasive procedures such as amniocentesis made screening for genetic abnormalities a much more risky procedure than it is today. Because of that only high risk cases were recommended to be screened. The good news is that today noninvasive prenatal testing poses no risk whatsoever to either the mother or the child so there really isn’t a valid reason to not have it done. So whether or not you are considered high risk it really does make sense to have your child screened. If anything else screening your child will give you the peace of mind of knowing that your child will likely be a happy and healthy one.

*     *     *

Preclinical Data Show Promise for Diabetic Eye Drug

Diabetic macular edema progression

Progression of vision loss from diabetic macular edema — Left: normal vision, Middle: blurred vision from diabetic macular edema, Right: floating spots from hemorrhages in the eye. (National Eye Institute, Verseon Corp.)

26 June 2017. Early evidence shows a drug designed as eye drops to treat diabetic macular edema, an eye disease in people with diabetes, permeates the entire eye, including the retina. Verseon Corp., a biotechnology enterprise in Fremont, California developing the drug, presented its results on 22 June at the annual meeting of the Biotechnology Innovation Organization, or BIO, in San Diego.

Diabetic macular edema can cause blurred vision and severe vision loss leading to blindness. It occurs when diabetes damages blood vessels in the eye, a condition known as diabetic retinopathy, resulting in leakage of blood and fluid, as well as swelling. Centers for Disease Control and Prevention says diabetes is the leading cause of new cases of blindness among adults aged 20 to 74. In 2011 the agency reported that from 2005 to 2008, some 4.2 million individuals — 28.5 percent of people with diabetes aged 40 years or older  — had diabetic retinopathy.

Most treatments today for diabetic macular edema require individuals to receive laser treatments or injections into the eye that reduce leakage from damaged blood vessels and the swelling that goes with it. Verseon’s treatment, as yet unnamed, addresses the plasma kallikrein-kinin system, a pathway producing peptides that encourage inflammation and dilation of blood vessels, activated when blood vessels are injured. The company says its formulation is designed to be administered as eye drops, instead of invasive lasers or injections, to block plasma kallikrein-kinin peptides in the eyes.

Verseon’s platform is based on computational modeling of molecular interactions. The company says it writes algorithms that integrate and optimize synthetic and natural chemical compounds, resulting in the design of new synthetic drug treatments. Its current products in development include an anti-coagulation drug — its lead product — and treatments blocking the rapid proliferation of new blood vessels in solid tumors, as well as the diabetic macular edema drug.

At the BIO meeting, Verseon presented results of its first tests of the diabetic macular edema drug on lab animals. The company says its drug, given with systematic doses, successfully infused into and throughout the eye, including to the back of the eye, where the retina is located, the part of the eye damaged by the disease. In addition, tests with other formulations of the drug show through activity in the body it could be given as an oral drug, as well as eye drops.

David Kita,  a founder of Verseon in 2002 and the company’s vice president for R&D, gave the BIO presentation. Verseon’s executives and staff combine offer expertise in physics, mathematics, medicinal and synthetic chemistry, biology, computer science, and early-stage drug discovery.

More from Science & Enterprise:

*     *     *

Immune Disease Start-Up Raises $28M in Early Funds

Vaccine syringe

(FirstResponder.govv)

26 June 2107. A new company founded to develop treatments for diseases caused by problems with the immune system is raising $28.4 million in its first round of financing. Provention Bio Inc. in Lebanon, New Jersey plans to address autoimmune disorders, where the immune system is tricked into attacking healthy cells and tissue, either by preventing the diseases or with early-stage treatments before serious symptoms emerge.

Provention Bio began last year, started by Francisco Leon, an immunologist and founder of several biotechnology and drug discovery companies, and Ashleigh Palmer, a venture investor and also a founder of multiple life sciences enterprises. The company obtains the rights to promising drug candidates designed to prevent the onset of autoimmune diseases — such as type 1 diabetes, Crohn’s disease, and ulcerative colitis — or treat the disorders early in their progression before symptoms become more serious, or prevent their relapse in cases where the disease is already taking hold.

Provention says its first discoveries are licensed from Janssen Research & Development, a division of drug maker Johnson & Johnson, and Vactech Oy, a biotechnology company in Tampere, Finland. Vactech is developing a vaccine to prevent type 1 diabetes, an inherited disorder where the immune system attacks insulin-producing beta cells in the pancreas, and is diagnosed primarily in children or young adults. The vaccine is designed to prevent infections from enteroviruses, a type of virus responsible for a wide range of diseases, but also suspected of being a triggering mechanism in type 1 diabetes. Vactech says preclinical tests suggest its vaccine could prevent as many as half of all type 1 diabetes cases.

Leon and Palmer are also founders of the CelImmune, a biopharmaceutical company developing treatments for celiac disease, also an inherited disorder. As reported in Science & Enterprise, CelImmune is conducting a clinical trial of a therapy for advanced cases of celiac disease that do not respond to a gluten-free diet.

MDB Capital Group in Dallas is a co-founder of Provention Bio as well as leading the funding round. Taking part in the financing are Johnson & Johnson Innovation and the investment arm of JDRF, a foundation raising money and awareness to support research on type 1 diabetes. JDRF is collaborating with Janssen Research & Development on developing early stage treatments for type 1 diabetes. Janssen R&D has a division called its Disease Interception Accelerator addressing conditions in their early stages, including type 1 diabetes.

MDB Capital completed the $28.4 million fund-raising in April 2017, through sales of preferred shares of Provention stock that have a higher claim on assets and earnings than common stock. An initial public offering of Provention common stock is expected next year.

More from Science & Enterprise:

Disclosure: The author owns shares in Johnson & Johnson.

*     *     *

Algorithm Quickly Customizes Walking Exoskeleton

Foot-ankle exoskeleton

Foot-ankle exoskeleton used in the study (Carnegie Mellon University)

23 June 2017. Researchers at Carnegie Mellon University in Pittsburgh wrote and tested an algorithm for exoskeletons that customize the devices to a person’s walking pattern in about an hour. A team from the lab of engineering professor Steven Collins describes its work in today’s issue of the journal Science (paid subscription required).

Exoskeletons are lightweight frames with sensors and motors worn like braces over the legs that provide at least some walking ability to people who are paralyzed, fit over prosthetic devices to help amputees walk, or provide more mobility to individuals with limited ability to walk, such as people recovering from a stroke. The devices work by supporting a person’s weight and assisting the muscles to move the legs in a walking motion.

The technology in exoskeletons improved over the years, becoming smaller, lighter, and more finely attuned to different muscles needing support, but they remain basically a one-size-fits-all device. Collins and colleagues sought a way of personalizing the devices to a person’s unique walking motion. The solution, however, would need to work quickly and make the necessary adjustments to the exoskeleton in near real time.

The Carnegie Mellon team focused its solution on the actions of ankles and feet, using an exoskeleton developed to help with rehabilitation for individuals learning to walk with a prosthetic device on the lower leg, or in recovery after a stroke. The device has sensors implanted that measure the energy expended and torque, or rotational force, patterns when walking.

The researchers use data from the sensors to note subtle differences in the walking patterns between the two ankles and feet, measuring peak torque and the timing of that rotational force on each ankle, as well as the rise and fall times of each foot. Their system collects data for about an hour from an individual testing the exoskeleton, then an algorithm adjusts the torque support provided on the exoskeleton to minimize the amount of energy expended by the user.

The team tested the system with 11 healthy volunteers wearing the exoskeleton and walking on a treadmill. The system found wide variations in walking style, which required different adjustments in support provided by the exoskeleton, as well as underscoring the need for customization of these devices. With an optimized exoskeleton worn on one foot and ankle when walking, the researchers found the users expended on average about 24 percent less energy, compared to a similar exercise wearing the exoskeleton without the customized adjustments.

Similar results were recorded when individual participants wore personalized exoskeletons on both ankles and when running. Other participants who wore the exoskeletons for extended periods found the systems continued to find adjustments for the devices, suggesting an individual’s walking patterns continue to change and that personalized exoskeletons may need further adjustments over time.

The authors believe this approach to prosthetics could make possible faster and more personalized rehabilitation, taking more factors into account, such as endurance and balance. Prosthetic devices could also be adjusted over the course of a person’s rehabilitation as they move into their day-to-day lives. Likewise, devices could be monitored and adjusted over time as their circumstances change or conditions improve.

More from Science & Enterprise:

*     *     *

Long-Acting Drug Blocks Opioid Effects, Withdrawal

Pills in blister packs

(PublicDomainPictures, Pixabay)

22 June 2017. Findings from a clinical trial show a formulation of the drug buprenorphine given once a week blocks effects of subsequent opioid exposure and withdrawal symptoms. Results of the trial appear in today’s issue of the journal JAMA Psychiatry and were presented at a meeting of the College on Problems of Drug Dependence now underway in Montreal.

The intermediate-stage clinical trial is testing a drug code-named CAM2038 made by Braeburn Pharmaceuticals in Princeton, New Jersey, and Camurus AB in Lund, Sweden to treat opioid use disorder. Opioids work by reducing the intensity of pain signals to the brain, particularly regions of the brain controlling emotion, which reduces effects of the pain stimulus. Examples of leading opioid prescription pain medications are hydrocodone, oxycodon, morphine, and codeine. Heroin is also considered an opioid.

The U.S. Department of Health and Human Services says the country is in the midst of a “prescription opioid overdose epidemic.” In 2014, according to Centers for Disease Control and Prevention, more than 28,000 people died from opioid overdose, and at least half of those deaths involved a prescription opioid, with even more becoming addicted to prescription and illegal opioids. Heroin-related deaths also increased sharply, more than tripling since 2010, leading to more than 10,500 deaths.

CAM2038 is a formulation of the drug buprenorphine that acts on the same receptors in the brain as heroin and morphine, providing enough satisfaction of those receptors without producing the intense “high” or serious adverse effects of abused drugs. Camurus adapted its injection technology that the company calls FluidCrystal for CAM2038 that combines buprenorphine with a liquid lipid solution to form a gel that that can be injected, yet breaks down slowly in the body to allow for release over extended periods of time.

CAM2038 is designed for delivery via injections under the skin by clinicians, as part of anti-addiction therapy, and can be adjusted for the length of time buprenorphine needs to be released, in this case 1 week. The 47 participants, adults in treatment for moderate or severe opioid use disorder, were randomly assigned to receive injections of CAM2038 at doses of 24 or 38 milligrams on the first day of the trial, then once a week for the next 2 weeks.

During the first 3 days, participants also received injections of varying doses, 0 to 18 milligrams, of the opioid drug hydromorphone, given for chronic moderate to severe pain, then when receiving CAM2038 later on. Participants were asked to report on questionnaires at 4 different points during the test period on their desire to use opioids, liking of drugs, alertness and drowsiness, and experiences of drug highs, as well as good and bad drug effects. Individuals in the trial were also given physical exams that recorded their vital signs, heart functions with electrocardiograms, depression, and adverse effects from CAM2038 or other causes. In addition, participants provided blood samples before and after CAM2038 injections.

The results show participants receiving either dose of CAM2038 blocked the effects of hydromorphone, reported in the self-described desire for opioids and liking of drugs. Individuals in the trial also suppress withdrawal symptoms when empty (0 milligram) doses of hydromorphone were given. The effects were supported by blood tests showing continued concentrations of buprenorphine in the plasma of participants several days after the injections.

Most (81%) of participants experienced some adverse reactions during the trial, usually mild, including constipation, pain at the injection site, skin irritation, headache, and nausea. One individual had to discontinue participation and another developed hepatitis C, in both cases due to causes other than CAM2038.

CAM2038 is currently in a late-stage clinical trial and long-term safety study. Braeburn and Camurus expect the results of these studies will support regulatory approval in the U.S. and Europe.

More from Science & Enterprise:

*     *     *

Computer-Designed Antibodies Target Alzheimer’s Proteins

Mouse brain with amyloid-beta

Mouse brain nerve cells, green, with amyloid-beta plaque accumulations, blue (NIH/Flicker)

22 June 2017. Researchers in Europe designed antibodies, like those in the immune system, to attack protein deposits in the brain associated with Alzheimer’s disease. The team from the lab of chemistry professor Michele Vendruscolo at University of Cambridge in the U.K. describes its findings in yesterday’s issue of the journal Science Advances.

The Cambridge researchers, with colleagues from ETH Zurich in Switzerland and Lund University in Sweden, are seeking faster and more effective ways to find treatments for Alzheimer’s disease and other neurological disorders characterized by aberrant proteins. Alzheimer’s disease is a progressive neurodegenerative condition affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta proteins, as well as misfolded tangles of proteins inside brain cells known as tau.

Preventing these substances from building-up in the brain is a promising strategy for prevention or treatment of Alzheimer’s, but finding therapies that get results is elusive, due in large part to the complexity of the process that amyloid-beta and tau proteins accumulate. Most current drug discovery methods, such as screening large databases of compounds, is haphazard and so far not providing satisfactory results.

Vendruscolo’s lab takes a more direct approach to drug discovery, using computational methods to design drugs with the desired capabilities and features to achieve the desired outcomes, in this case prevent amyloid-beta proteins from accumulating in the brain. The team, led by Francesco Aprile, a postdoctoral research fellow and first author of the paper, designed an antibody like those in the immune system that attack specific invading substances. The researchers started with a clean slate, working largely from the sequence of amino acids in amyloid-beta proteins.

But because of the complexity of proteins building-up in the brain, the antibody had to meet demanding conditions. The team designed the antibody to address amyloid-beta proteins in the early stage of accumulation as they formed into oligomers, or small aggregates of amyloid-beta, before producing toxins. The researchers also targeted specific epitopes, or binding regions of the protein. To find these targets, the antibody scans the amino acids in the amyloid-beta proteins until the matching epitope is found.

In addition, the antibody needed to be small in size, which serves two purposes. First, the small size makes it easier to cross the blood-brain barrier, a filtering mechanism in the brain and spinal cord to prevent toxins in the blood from affecting the central nervous system, but also prevents many drugs from treating neurological diseases. In making the antibody smaller, the team also removed components in the chemistry that trigger inflammation common to immune reactions. These inflammatory responses up to now made it difficult to use antibodies to treat Alzheimer’s disease.

The specific targeting and small size offer yet another advantage. “Since the designed antibodies can selectively target oligomers, which are present in low numbers relative to the total amounts of amyloid-beta,” says Aprile in a university statement, “we expect them to be effective even when administered in low doses.”

The team tested 2 antibodies designed to address initial and then secondary accumulation of amyloid-beta proteins. The lab tests, which included giving the proteins to roundworms that share some genetic characteristics with mammals, show the antibodies stop the over-expression of amyloid-beta proteins.

“Developing antibody-based therapies is costly and time-consuming,” notes Vendruscolo, “but if we can find better and cheaper ways of producing antibodies, we would increase the chances of finding treatments for patients. Making them by design can create opportunities to achieve this goal.”

More from Science & Enterprise:

*     *     *

Commercial-Scale Flu Vaccine Produced in Cell Cultures

Vaccine processing vessel

Vaccine processing vessel at Holly Springs, North Carolina plant (Seqirus)

21 June 2017. A vaccine developer says it produced large quantities of a current influenza vaccine for distribution to clinics and hospitals, grown in animal cell cultures rather than eggs. Seqirus, a division of CSL Limited, says the vaccines were made at its plant in Holly Springs, North Carolina, the first time flu vaccines were produced with this process on this scale.

Most flu vaccines today are grown in chicken eggs from a candidate vaccine, a process that can take months to produce in sufficient quantities to protect populations. Candidate vaccine strains are first identified by public health authorities, working with World Health Organization, then WHO generates candidate vaccine viruses that developers use to mass-produce the vaccine doses given to individuals.

Growing vaccines in eggs is needed for virus incubation and actual production before the vaccine is delivered, a process that often takes many months. As a result, WHO and other public health authorities need to identify specific influenza strains well in advance of their actual distribution, which means new strains can emerge after vaccine producers begin making doses for the public, but still before the traditional flu season. This problem occurred in 2015, when the H3N2 flu virus emerged after producers began making vaccine doses that did not cover that strain.

Growing vaccines in mammal cell cultures is already in practice to produce vaccines for polio, rubella, and hepatitis, but has been problematic when tried on a large scale for most flu viruses. The mammalian cell process makes it easier to maintain an adequate supply of production-ready cells for vaccine manufacturing, and reduce the time needed to start up vaccine production in the event of a pandemic. Clinical trials show flu vaccines grown in animal cells are safe and perform at least as well as when grown in chicken eggs.

The problem up to now was scaling-up the process to produce enough vaccine doses for mass distribution. Seqirus says it produced for the first time the H3N2 vaccine in commercial quantities with mammal cell lines, beginning with a sample of WHO’s candidate vaccine, thus completely eliminating the use of chicken eggs. H3N2 strains are part of the 2017-2018 flu virus formula. The company says it plans to use mammal cell cultures for other vaccines at its Holly Springs plant.

The Holly Springs plant was built with support from the U.S. Biomedical Advanced Research and Development Authority, or BARDA, to help combat pandemic threats. The company says the facility was designed and constructed in collaboration with WHO and Centers for Disease Control and Prevention. FDA gave its approval in August 2016 to begin producing vaccines at the plant.

Seqirus is the former vaccines division of drug maker Novartis, acquired by CSL Limited in July 2015.

More from Science & Enterprise:

*     *     *