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A.I. Drug Discovery Company Gains $32M in Early Funds

Brain hemispheres graphic

(Pixabay)

16 July 2018. A company using genomic databases and artificial intelligence to discover new therapies for neurodegenerative diseases is raising $32 million in its first venture funding round. Verge Genomics, a three year-old enterprise in San Francisco says it combines neuroscience with machine learning and experimental biology to speed the discovery of drugs for disorders of the nervous system, beginning with amyotrophic lateral sclerosis, or ALS, and Parkinson’s disease.

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, the muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure.

Parkinson’s disease occurs when the brain produces less of the substance dopamine, a neurotransmitter that sends signals from one neuron or nerve cell to another. As the level of dopamine lowers, people with Parkinson’s disease become less able to control their bodily movements and emotions. Symptoms include tremors, i.e. shaking, slowness and rigidity in movements, loss of facial expression, decreased ability to control blinking and swallowing, and in some cases, depression and anxiety.

Verge Genomics says it discovers new therapies by intensive analysis of databases with genomic data from neuroscience research partners in the academic world and government. The company’s web site lists Scrips Research Institute, Genomics England that hosts the 10,000 Genomes Project, Massachusetts General Hospital, Columbia University, Johns Hopkins University, Center for Regenerative Therapies at Technical University Dresden in Germany, University of Michigan, and University of Southern California.

With these databases, says Verge’s co-founder and CEO Alice Zhang, the company uses machine learning algorithms to identify the most promising candidates for further development. But the company says it goes further to automate much of the drug discovery process to reduce many uncertainties contributing to the high costs, risks, and long timetables needed to develop new drugs. Only after this intensive process, do the company’s wet labs begin their drug development work. “By vertically integrating machine learning and drug development capabilities under one roof,” notes Zhang in a company statement, “we have been able to quickly identify dozens of promising new therapeutic opportunities for devastating diseases such as ALS and Parkinson’s disease.”

In a separate collaboration announced in May, labs at University of California in San Diego and VIB, a life sciences research institute in Belgium, are partnering with Verge to sequence the RNA in individual cells in brain tissue samples from people with Parkinson’s disease. Using Verge’s algorithm’s the partners aim to track changes in gene expression across different types of cells affected by Parkinson’s disease, compared to healthy brain tissue.

Verge Genomics raised $4 million at its founding in 2015. The new financing of $32 million, the company’s first venture funding round, is led by tech industry investor DFJ in Menlo Park, California that counts among its portfolio Twitter, Redfin, and Tesla and SpaceX founded by Elon Musk. Taking part in the round are WuXi AppTec’s Corporate Venture Fund, ALS Investment Fund, Agent Capital, and OS Fund. DFJ partner Emily Melton is joining the Verge Genomics board of directors.

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New Type of Graphene Circuit Designed for Biosensors

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Graphene illustration

(Maxpixel.net)

16 July 2018. The May 2018 chart in a report from CB Insights, a technology market intelligence company, had the ominous headline “Graphene deals steadily increased before dropping off,” showing an abrupt drop in venture investment funds for start-up companies in 2017 to $2 million, from its peak of $36 million just 2 years earlier. The report notes that, “The drop reflects a loss of traction typical in advanced materials development, where technology gets bogged down between breakthrough and commercialization.”

It’s not that graphene lacks inherent properties that make it a highly desirable material for today’s high performance technology. Graphene is a carbon material closely related to graphite like that used in pencils, but it consists of only a single layer of atoms arrayed in a hexagonal mesh pattern. The material is very light, strong, chemically stable, and can conduct both heat and electricity, with applications in fields such as electronics, energy, and health care.

For graphene to regain that market traction may require developing more applications that use a combination of its desirable properties. One of those emerging needs is for biosensors that can detect electrical and physiological signals in the human body, which require a high degree of sensitivity. As reported in Science & Enterprise in June, for example, researchers at University of California in San Diego enhanced the ability of graphene electrodes to better record optical images of brain activity, which they demonstrated in lab mice.

A more direct application of graphene in sensors for health care are field effect transistors, also known as graphene fets. These circuits have a semiconductor a channel with 3 electrodes, a source and drain electrode or terminal, connected by a gate electrode that controls the flow between the other 2 terminals. Graphene is used in the channel between the source and drain. Tests with graphene fets show a high degree of sensitivity needed in bio sensors.

One of those studies, conducted by University of Plymouth in the U.K., found sensors based on graphene fets could detect low concentrations of human chorionic gonadotropin, a protein biomarker for some types of cancers. But an even more urgent need for graphene may be in sensors for detecting opioid drug compounds. In another study led by physicists at University of Pennsylvania, researchers found graphene fets sensors could detect weak concentrations of naltrexone, an opioid receptor antagonist.

These high-priority health care needs may provide the commercial traction graphene needs to fulfill its promises as a wonder material.

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Exosome Technology Acquired for TBI, Stroke Therapies

Stroke circulation

(Gerd Altmann, Pixabay)

16 July 2018. A company developing therapies for brain injuries and neurodegenerative disorders is acquiring the rights to a process that treats these conditions with pieces of RNA transferred in tiny containers call exosomes. NeuroTrauma Sciences LLC, a two year-old company near Atlanta, is licensing the exosome transfer technology from the lab of Michael Chopp at Henry Ford Health System in Detroit. Financial details of the agreement were not disclosed.

Exosomes are tiny — 40 to 150 nanometer — lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes were shown in recent years to perform useful delivery functions carrying proteins and genetic material to other cells, and drawing increased attention from a range of biological disciplines.

Chopp is a neurologist at Henry Ford Health System and scientific director of its Neuroscience Institute. His lab at Henry Ford studies exosomes as vehicles for delivering therapeutics for stroke and traumatic brain injuries. In April 2018, Chopp and fellow Henry Ford neurologist Jieli Chen, published a paper in the journal Stroke, outlining methods and documenting previous studies for using exosomes derived from an individual’s mesenchymal stromal cells — similar to stem cells — to deliver personalized treatments for stroke.

Among the treatments for stroke that can be delivered with exosomes, according to Chopp and Chen, is micro RNAs, genetic molecules that serve as regulators of the genome. Micro RNAs start out small, but evolve into more complex molecules that interact with another type of RNA — messenger RNA — to control the expression of genes responding to various proteins. Chen led a study published in 2017, with Chopp as co-author, showing micro RNAs reduced neuroinflammation in lab rodents induced with stroke from diabetes. A separate study co-authored by Chopp and published last year shows molecules acting like micro RNAs reduce peripheral nerve damage in mice induced with type 2 diabetes.

“Our studies in multiple pre-clinical models,” says Chopp in a NeuroTrauma Sciences statement, “indicate that exosomes have the potential to provide significant therapeutic benefits to enhance the recovery from stroke or traumatic brain injury, and potentially with a better safety profile and greater efficacy than their parent or progenitor cells. Success of this novel approach may lead to a shift in the treatment paradigm for TBI, stroke and neurological disease.”

For this agreement, NeuroTrauma Sciences is forming a separate subsidiary called NeurExo Sciences to advance exosome-delivered micro RNAs as therapies for stroke, nerve damage, and traumatic brain injuries such as concussions. NeurExo Sciences is receiving a worldwide license to develop treatments for these disorders. The company is also funding further research on exosomes by Chopp’s lab, and will receive the rights to findings from the studies it sponsors.

Up to now, NeuroTrauma Sciences operated largely in stealth mode. The Alpharetta, Georgia company, founded in 2016, lists its executives on its web site, but does not identify its investors and gives few details about its work.

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Infographic – Top 10 Android Apps

Top 10 Android Apps

Click on image for full-size view. (Statista)

14 July 2018. This past week, Science & Enterprise reported twice on studies involving mobile apps that gave a mixed verdict about their value. On 11 July, an Australian team found mental health apps may be promoting their use with misleading guidance to individuals on the extent and seriousness of their psychological conditions. And yesterday, researchers at University of Iowa found a game app plus wearable devices increased the amount of exercise by usually sedentary office workers, but the effects declined over the next several weeks.

It may helps putting the value of these specialized apps into a larger context, namely the main reasons people add apps to their phones. Our friends at Statista compiled the chart above, with data from the market research company Priori Data, showing the top 10 Android app downloads in June 2018, this weekend’s infographic. The data show messaging, games, and social media are the most downloaded apps, which suggests the Iowa group may be on to something when they used a game format for their app. But the findings also show the dominance of Facebook in the mobile world, owners of 5 of the top 10 downloaded apps, including the top 2 downloads.

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Wearables, Game App Help Boost Exercise Levels

Woman walking and reading

(Francisco Osorio, Flickr)

13 July 2018. A study assessing FitBit devices and a game-style mobile app shows a combination of the technologies results in more exercise by office workers, at least at the outset, than just the FitBit alone. The findings of medical and informatics researchers at University of Iowa in Iowa City appear in the 3 July issue of the Journal of the American Heart Association.

A team led by Philip Polgreen, professor of epidemiology and internal medicine, and Lucas Carr, professor of physiology, are seeking more effective methods for people who sit all or most of the day in their jobs to get more exercise. The authors cite a number of statistics showing work environments becoming increasingly inactive, with more than 4 in 10 service jobs (43%), now considered sedentary. Moreover, people in office jobs spend as much as 89 percent of the time sitting, making them more susceptible for cardiovascular disease, diabetes, obesity, osteoporosis, and depression.

The Iowa researchers took an approach that tries to integrate exercise into individuals’ work days, rather than encouraging exercise before or after work alone. Polmgreen, who has a background in mathematics as well as medicine, enlisted colleagues in the university’s computer science department to write a smartphone app called MapTrek that overlays the number of steps taken by users to various scenic places, such as the Grand Canyon or Appalachian Trial, using the Street View feature of Google Maps. MapTrek takes data from accelerometers, such as those in FitBit devices that measure activity, and moves avatars through the mapped territories, where individuals can track their progress. The app also has group features enabling users to post their results compared to others, and hold competitions within the groups.

Polmgreen, Carr, and colleagues recruited office workers for a clinical trial testing the ability of Fitbit devices and the MapTrek app used as a game with competitions among participants, compared to FitBit devices alone. The 146 participants enrolled in the study and who sit at least 75 percent of the time in their offices, were randomly assigned to use FitBits and MapTrek, or just wear the FitBit device. The researchers from Polmgreen’s and Carr’s labs then tallied the number of steps per day, and amount of activity time each day, recorded by the devices for 10 weeks.

The results overall show participants using the MapTrek app and FitBit devices recorded nearly 2,100 more steps per day and were active 11.2 more minutes per day than the FitBit only participants. In both groups, individuals began taking part enthusiastically, but the number of steps and activity time per day dropped steadily during the 10-week period. While the MapTrek and FitBit participants continued to report more steps taken per day throughout the test, by the end of the 10 weeks the FitBit only participants were spending slightly more time being active than the MapTrek and FitBit group.

“Over 10 weeks, the gains in activity declined and the two groups looked similar by the end of the study,” says Polmgreen in a university statement. “But, we are encouraged by the big initial increase in daily steps and are now looking to improve the game in ways that result in longer changes in behavior.” Carr adds, “The value of this kind of approach is virtually anyone can play it with minimal risk. Nearly everyone can benefit from increased levels of activity.”

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Tech In The Classroom – Why Is It So Important?

– Contributed content –

Empty classroom

(Wokandapix, Pixabay)

13 July 2018. The world is becoming a lot more dependant on technology these days, and that is becoming increasingly clear in most schools’ classrooms. There are now a lot of tech devices, such as interactive whiteboards, that some teachers are bringing into lessons to encourage children to learn throughout their classes. Some believe that the use of tech is a great benefit to children. However, no all teachers are in agreement about this, and some still believe that tech should be left out of the classroom. But is that really the case? Here are some great benefits of tech in the classroom, most of which can’t be ignored.

Helps stimulate pupils

One of the main reasons why so many teachers love using technology and devices in the classroom is that it keeps the attention of pupils. That’s largely because it is a great stimulant. Children respond really well to technology, especially when it provides them with some interactive features. Not only that, though, but it can help to demonstrate some concepts and theories that might be difficult to otherwise explain, such as evolution.

 

Tackles student problems

Most teachers find that technology is a great aid in tackling the issues that problem students bring. For instance, it can help to speedily resolve any problems. Take the modern service to remove graffiti – removing this kind of vandalism on school property is a great way to show pupils that it will not be tolerated. That’s not all, though. Most teachers who regularly use tech in their lessons find that even the most problematic of students still pay attention as they are so bowled over with all the tech.

Encourages global learning

Thanks to the internet, the world is now a lot smaller than what it used to be. And that means that it is now possible to bring some global learning in to the classroom, which can be especially useful in foreign language lessons. For instance, teachers can connect to other schools around the world using applications like Skype, which is great to encourage pupils to practice their speaking skills.

Cuts down costs

Using digital tools and technology can also cut down on the usual costs and expenses that schools have previously faced. After all, when learning predominantly takes place on interactive whiteboards, there is not much need for paper and exercise books. So, if more classrooms were to move to tech tools, they could see some of their traditional expenses disappear, which could save many schools a lot of money.

Promotes digital citizen skills

We all need tech skills in this day and age as our lives are becoming a lot more dependent on various forms of technologies. By gaining these kinds of skills, we become digital citizens and are better equipped to succeed in the digital world. When schools bring tech into the classroom, they are aiding children by equipping them with the skills they will need later in life.

So, what do you think about bringing technology into school classrooms?

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RNA Nanoparticles Designed for Brain Cancer Therapy

Brain cell networks

(Gerd Altmann, Pixabay)

13 July 2018. Medical researchers and material scientists devised a technique for delivering tiny particles of genetic material to the brain, which help lab mice shrink or remove their brain tumors and survive longer. A team from Johns Hopkins University in Baltimore describes its process and results in a recent issue of the journal Nano Letters (paid subscription required).

The Johns Hopkins researchers led by cancer specialist John Latera and bioengineering/materials science professor Jordan Green are seeking better treatment options for glioblastoma, an aggressive brain cancer that affects astrocyte or glial cells supporting neurons or nerve cells in the brain. Glioblastoma is often difficult to treat, where usually the best hope is to slow progression of the disease with radiation or chemotherapy. Survival from initial tumors is typically 20 months and those with recurring glioblastoma usually survive for less than a year.

Among the difficulties in treating glioblastoma are the resilience of cancer stem cells and the blood-brain barrier. Cancer stem cells, say the authors, are able to reproduce themselves and sustain the cancer, even after tumors are removed by surgery, allowing them to spawn more tumor cells. The blood-brain barrier is a mechanism that prevents molecules from crossing from the blood stream into brain cells. Blood vessels in the brain form a support network for brain functions, with tightly-packed cells lining blood vessels that allow nutrients to pass through, but keeping out foreign substances, including drugs to treat neurological conditions.

Even if the blood-brain barrier can be pierced, brain cancer therapies still need to be carefully targeted to attack only tumor cells and not healthy tissue. To meet these objectives, the Johns Hopkins team designed tiny nanoscale particles — where 1 nanometer equals 1 billionth of a meter — that deliver micro RNAs, genetic molecules that serve as regulators of the genome. They start out small, but evolve into more complex molecules that interact with another type of RNA — messenger RNA — to control the expression of genes responding to various proteins.

In this case, the micro RNAs bind to messenger RNAs with instructions from 2 genes, HMGA1 and DNMT, that regulate gene expression and provide repair and stability for genes. By targeting the 2 genes, the micro RNAs block production of proteins that support the most dangerous properties of cancer stem cells, making them less likely to propagate and more susceptible to cancer treatments like drugs or radiation. The micro RNAs are packed into nanoscale particles made from a biodegradable polymer called poly(beta-amino esters) or PBAEs, already in use for gene therapies.

The researchers tested micro RNA nanoparticles with 18 lab mice implanted with human glioblastoma. All of the mice received nanoparticles with micro RNAs about 6 weeks after the tumor implantations, but in only 9 of the 18 mice were the micro RNAs activated. The results show the mice receiving the activated nanoparticles survived from 80 to 133 days, while the inactive nanoparticle recipients lived no more than 90 days. In the longer-surviving mice, their glioblastoma tumors were sharply reduced in size or completely disappeared, while mice receiving the inactive nanoparticles showed little or no evidence of tumor shrinkage.

The team believes the findings prove the concept of micro RNA delivery with nanoparticles, but the process needs more development to meet human scale demands, such as catheters or pumps to move the nanoparticles through the larger human brain. Nonetheless, the researchers filed for a patent on the technology.

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Trial Testing Vitamin D, Fatty Acids for Type 1 Diabetes

Diabetes word cloud

(905513, Pixabay)

12 July 2018. A clinical trial is underway testing vitamin D and omega-3 fatty acids in children and adults as a treatment for type 1 diabetes, the form of diabetes where the body does not produce insulin. The trial is led by and conducted at the Diabetes Research Institute at University of Miami in Florida.

Type 1 diabetes is an inherited autoimmune disorder where the beta cells in the pancreas do not produce insulin, and is diagnosed primarily in children or young adults. Autoimmune disorders are conditions where the immune system is tricked into attacking healthy cells and tissue as if they were foreign invaders, in this case, insulin-producing beta cells. From 5 to 10 percent of people diabetes have the type 1 form, estimated at 1.25 million people in the U.S.

Miami’s Diabetes Research Institute is exploring the benefits of vitamin D and omega-3 fatty acids, found in fish and some oilseed plants like flax for people with type 1 diabetes. Among other benefits, omega-3 fatty acids have anti-inflammatory properties and are believed to improve immune system functioning. The institute team believes these properties can be translated into help for people with type 1 diabetes, to slow the progression or even stop the disease entirely.

Camillo Ricordi, director of the institute, says in an institute statement, “Results from our recent case studies examining the role of omega-3 and vitamin D in preserving beta cell function in three pediatric subjects with type 1 diabetes warrant further investigation of this potential therapeutic strategy.” Results of these cases were published in July 2016.

The early- and intermediate-stage clinical trial is recruiting 56 individuals with type 1 diabetes in a pilot test of these treatments. Participants range in age from 6 to 65, but must be diagnosed with the condition within the past 10 years. The group is randomly assigned into 4 sections, each with 14 participants, and 2 groups each of children and adults, divided further into those with type 1 diabetes that began within the previous 6 months, and those with the disorder for more than 6 months. The trial is testing high doses of cholecalciferol, a vitamin D dietary supplement only, compared to cholecalciferol plus highly refined omega-3 fatty acids derived from fish oil, over 1 year.

Individuals in the trial will be evaluated primarily for the ability of their bodies to produce insulin. Participants will be given a Mixed Meal Tolerance Test, usually a standard dietary mixed meal, such as the commercial supplements Boost or Ensure. Blood tests then measure blood glucose levels in response to the meal. These tests will be given over the 1 year period, as well as measures of insulin requirements and signs of adverse effects over the period.

“If combination omega-3 and vitamin D therapy is able to delay progression or halt autoimmunity in type 1 diabetes,” notes Ricordi, “this is expected to result in retention of insulin secretion, minimal use of exogenous insulin, and improved metabolic control thus minimizing the risks associated with unstable blood glucose levels.” The researchers believe if the trial is successful, the strategy may also benefit patients with other autoimmune disorders, such as Crohn’s, rheumatoid arthritis, and lupus.

Ricordi tells more about the trial in the following video.

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Don’t Fall for These Common Business Tech Events

– Contributed content –

Man at desk

(Maxpixel.net)

12 July 2018. Every business needs to use some type of technology. Whether you start off with a single computer or you immediately have a large collection of sophisticated equipment, you need to be able to manage the tech that your business needs. Many businesses, both new and established, can experience various problems where technology is concerned. Mistakes are easy to make if you don’t know much about technology. Fortunately, they’re also easy to avoid, if you know what to be aware of. Read the advice below if you want to avoid making some of the biggest tech mistakes that businesses fall for.

Not having a plan

You should always have a plan for doing anything. You might not know exactly what your business will look like in the future, but you should have an idea of what you want it to look like. And if you have a plan for your business’s growth, you should also have a plan for the growth of your IT infrastructure. You’re going to need the appropriate technology to support your growing business. You might start off with a single computer, but you’re soon going to need more. When you create a plan for growth, don’t forget to consider technology and its role in your business.

Not having any tech support

You might think that you don’t have much of a need for tech support. However, as your company grows, it’s going to get more and more important. Even while your business is small, you can still benefit from some technical support. What happens when your one computer goes wrong? What if your internet connection isn’t working? Some technical support might be available from a current service provider or a retailer you bought a product from. If your company is small, you can get support from a care and support package for particular hardware or software. As you grow, there are scalable support options available for your IT.

Not ensuring adequate security

Security is vital when it comes to protecting your business technology. But too many businesses can be lax about keeping their technology secure. You might think you’re maintaining good security, but you might not be doing as good a job as you thought. It’s essential to have the right protection against viruses and cybercrime. It’s also important to keep everything up to date. If you install all the right measures but then neglect them, they won’t remain effective. Any security incidents could end up costing you a lot of money, especially if you don’t protect customer information properly.

Laptop, notebook, pen

(Gournbik, Pixabay)

Thinking that all website design is the same

A website is an essential part of any business’s online marketing strategy. Some companies start by building a small site themselves, but they quickly discover that they need something more. If you decide that you need to find a website designee, you need to brush up on your knowledge about web design and development. It’s a good idea to know the UI and UX difference so that you can find the right person to build your website. Don’t make the mistake of thinking that all website designers will do everything that you need. Some specialize in creating the right look for your site, while others focus on its function. Some will do both but not all of them do.

Getting all the shiny tech

It’s very tempting to try and get all of the cool tech for your company. Maybe you’re aiming to be modern and up-to-date, and you want to get ahead of your competitors. But you can’t spend all your money on technology that might not even end up being as useful as you hoped. There’s no need to constantly get the new thing. That’s an expensive way to manage your tech, and it could mean that you spend half your time implementing new tools. Before you buy anything new, you need to consider the costs and benefits of doing it. Are you going to have to spend lots of time training your staff to use a new tool? How will it really benefit your company in terms of productivity, profit and other important factors?

Concentrating too much on software

Choosing the right software is important. However, it’s important not to neglect hardware when you’re thinking about your business technology. You could have some fancy software, but it’s not going to work well for you if your hardware is inadequate. Having the right hardware can often be more beneficial if you want to get things done faster and smoother. Before you consider any new software, think about whether updating your hardware could offer you the most benefits.

Failing to train staff

Whenever you add new technology to your business, you need to make sure everyone can use it. If you don’t train your staff, you might as well not bother implementing any new technology. It can take time and money, but you need to make sure that the relevant people know how to use any new tools. When you’re deciding whether to invest in anything new, the usability is vital to consider. Your employees need to be able to learn how to use new technology without too much trouble. The more they need to learn, the more time and money it will cost you to implement.

Thinking you can do it all yourself

You should make sure that you seek out help for various aspects of your business technology. Many people assume that they can do all or most things themselves, when it might not be that easy. Even if you have the technical knowledge to do a lot of tasks yourself, you probably don’t have the time. If you want to concentrate on growing your business, you can’t spend too much time sorting out technical issues. Get someone else to do the busy work so that you can concentrate your energy where it’s needed most.

You can’t avoid making all mistakes, but you can know which ones are important to watch out for. Even if you do make a mistake, at least you can learn from it.

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FDA Issues Draft Gene Therapy Regulatory Guidance

Editing DNA

(LaCasadeGoethe, Pixabay)

11 July 2018. Food and Drug Administration issued a series of draft documents spelling out its processes for reviewing gene therapies for three types of diseases, as well as producing and testing these treatments. The six new guidance documents released for public comment were announced today in a statement by FDA commissioner Scott Gottlieb on the agency’s web site.

The proposed regulatory framework covers new drug applications for therapies where healthy genes are transferred into a patient’s genome that replace missing or defective genes, as well as those that change genetic sequences, such as with genome editing. These treatments are being tested for inherited disorders, as well as autoimmune conditions, cardiovascular disease, cancer, and HIV/AIDS. Gottlieb says in his statement that even though the agency already reviewed and approved three gene therapies, the field is still new and its staff is still learning. He notes …

In contrast to traditional drug review, some of the more challenging questions when it comes to gene therapy relate to product manufacturing and quality, or questions about the durability of response, which often can’t be fully answered in any reasonably sized pre-market trial. For some of these products, we may need to accept some level of uncertainty around these questions at the time of approval.

Three of the documents address gene therapies for specific sets of diseases. One document spells out the agency’s thinking for review of gene therapies for hemophilia, an inherited blood disease. People with hemophilia lack a protein called a clotting factor that helps blood platelets coagulate around a wound. The two main types of the disorder are hemophilia A and B, where individuals lack clotting factor 8 or 9 respectively. About 8 in 10 people with hemophilia have type A. The guidance document outlines recommendations for designing clinical trials to test gene therapies, measurements for clotting factors 8 and 9, and preclinical steps for gene therapy developers. As reported in Science & Enterprise, FDA recently stopped a clinical trial from beginning in a test of genome editing for sickle cell disease, another inherited blood disorder.

A separate document highlights the agency’s approach to reviewing gene therapies for diseases of the retina, the layer of nerve cells on the back wall inside the eye that senses light and sends signals to the brain. One of the gene therapies approved by FDA in December 2017 is a treatment for inherited retinal disease made by Spark Therapeutics, also as reported by Science & Enterprise. The draft guidance provides recommendations for product development, as well as manufacturing considerations that take into consideration the fragile nature of eye tissue. The document also recommends preclinical studies with larger animals than lab mice or rats, to better approximate human eye size and complexity.

Another document covers gene therapies for rare diseases, while individually having small numbers, affect some 25 million people in the U.S., with children making up about half of that population. FDA says some 80 percent of rare diseases are caused by defects in single genes, making them good candidates for gene therapies. Because of small numbers of people affected with individual rare diseases, however, clinical trials of their treatments, including gene therapies, are more challenging. As a result, FDA recommends in the document more emphasis on preclinical studies to determine risks and benefits of proposed therapies. In clinical trials, the agency may consider alternatives to the classic randomized design testing experimental treatments against a placebo, such as single groups of patients with results compared to historical records, within specified limits.

FDA issued three other guidance documents on gene therapies for comment: (1) chemistry, manufacturing, and control information required for investigational new drug applications for gene therapies, (2) special requirements in retroviral vector-based gene therapies to protect against replication-competent retroviruses that pose serious risks to patients, and (3) long-term follow-up studies of gene therapies, looking particularly for delayed adverse effects.

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