Category Archives: Genetic Medicine

According to the American Academy of Dermatology, acne affects up to a staggering 50 million Americans annually.

To make matters worse, blackheads, whiteheads, pimples, cysts and other acne-related blemishes seem to occur at the most inconvenient times: before a date, a meeting, class photos, you name it. Although acne is not a serious health threat, severe acne can lead to disfiguring and permanent scarring.

Why do I have acne? Acne is most commonly linked to the changes in hormone levels during puberty, but can start at any age. Certain hormones cause the grease-producing glands next to hair follicles in the skin to produce larger amounts of oil, or abnormal sebum. This abnormal oil changes the activity of harmless skin bacterium called P. acnes, or propionibacterium acnes, which becomes more aggressive and causes inflammation and pus. Certain medications, stress and a poor diet can also contribute to acne. There is also evidence of a genetic component to acne as well.

Types of treatments: Because acne is caused by a myriad of factors, treating it with one product or medicine usually is not enough. You may need to attack it from many angles with different types of treatments that all work differently.

While a pimple will eventually go away, if you have numerous outbreaks, you could end up with scars. This is when it is time to visit a dermatologist, who may suggest a cream, lotion, gel or some that contains ingredients that can help. Many can be bought without a prescription:

Benzoyl peroxide kills bacteria and removes extra oil.

Salicylic acid keeps pores from getting clogged.

Sulfur removes dead skin cells.

Stronger treatments: If some of these over-the-counter remedies do not get your acne under control, your doctor may prescribe a retinoid to be used on the skin. This comes in a cream or gel and helps unplug oil ducts. Antibiotics in cream, lotion, solution or gel form may be used for inflammatory acne.

Isotretinoin is a medicine used to treat severe acne. It is usually used for cystic acne that does not improve after treatment with other medicines. Brand names include Accutane, Amnesteem, Sotret and Claravis. Isotretinoin is the most effective long-term medication for acne but is associated with some risks that dermatologists are familiar with. Spironolactone blocks excess hormones.

When to seek medical help: Even mild cases of acne can cause distress and, in some cases, depression. If your acne is making you feel unhappy or you are having a hard time controlling your blemishes with over-the-counter medication, see your doctor. Try to resist the temptation to pick or squeeze the spots, because this can lead to scarring.

Treatments can take a few months to work, so do not expect immediate results. Once they do start to work, the results are usually good.

Dr. Daniel Shurman of Pennsylvania Dermatology Partners in Amity Township completed his dermatology training at Thomas Jefferson University. He is fellowship-trained in both Mohs micrographic surgery and procedural dermatology, and his research interests include medical genetics, antibiotics in dermatologic surgery and wound healing.

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Here are some tips, treatment options for acne - The Reporter

Scientists are racing to learn more about a new coronavirus that has swept through China and spread across the globe.

The virus, which may have jumped from animals to people at a market in the city of Wuhan, has killed 259 people and infected at least 12,000.

The World Health Organization (WHO) declared the coronavirus outbreak a global public-health emergency on Thursday. The declaration has only been used five timessince it was created in 2005.

Scientists worldwide are trying to study the coronavirus and potentially develop a vaccine. Nature identified over 50 English-language studies on the virus published since January 12. More than 30 were published in pre-print servers without peer review, since the peer-review process can take months, and this virus is spreading quickly. A handful appeared in peer-reviewed journals, however.

"The primary benefit is probably in scientists being able to improve their work, to see what other scientists are working on, and come up with some consensus," Maia Majumder, a computational epidemiologist at Boston Children's Hospital and Harvard Medical School, told Wired. "For outbreaks especially, I think no matter how hard a journal tries to make review as rapid as possible, there's still going to be a delay."

Although it's preliminary, here's what published research has shown so far.

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Coronavirus research suggests 75,800 people in Wuhan could be infected - Business Insider - Business Insider

Investment Thesis

Objective: Wealth-building of an always fully-invested portfolio via repeated near-term (weeks or months) capital gains from careful, diversified, odds-on issue selection and timely price opportunity capture.

The stocks compared here are Sarepta Therapeutics, Inc. (NASDAQ:SRPT) and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR). SRPT was inadvertently omitted from the Biotech Developer review recently published. Rather than picture it by itself, ARWR is provided here as a best-ranked alternative.

These market pros have insights you and I can't have because their everyday job is to satisfy investment organizations running billion-dollar portfolios who want to adjust their holdings in multi-million-dollar trade transactions. These market-makers [MMs] have to round up sellers when their clients want to buy, and buyers when they want to sell. That's hard to do when most investors will hold off to get better prices, whether they are buying or selling.

And when lots of money is involved in each trade, the players get pretty careful about what they want to do and when they will do it. But the big-money types work hard to be on top of developments, following some issues intently, anticipating what is likely to be happening to stock prices in the near future. Depending on what they know, or think they know, and what they think others believe is likely to happen, they may take surprising postures. Often their holding-period horizons are months, not years. Or even less.

So, the MMs have to respond when a big-money house says "sell a bunch of this and buy a lot of that, and do it in the next 15 minutes, or you can forget about keeping us as a good repeat-order client".

The MMs will round up any of their other clients who they know have holdings in the stocks or appetites (at a price) to initiate, expand or contract holdings in the issues involved. It's rare when a "cross" can be made with enough "other side of the trade" exists at acceptable prices to "fill" the trade order without having to put some of their own firm's capital at risk in order to balance buying demand with selling supply.

As market-makers, they will provide the balancing position when they can set up a hedge deal to protect the market risk involved in their "facilitation" of the trade's being completed. If they can't, then the trade order gets killed, not filled, to wait for a time when the market is more accommodating.

But what it takes to buy that market risk price-change protection for the MM tells what the players on both sides of the "insurance" market believe can happen to the stock's price during the limited lives of the derivative contracts for options, futures, swaps, or other highly leveraged involved instruments used in the hedge.

That's where we find the balances between forecast upside price gain prospects and price drawdown exposures today and can compare them with what has been seen day by day over the past couple of decades. That is what supports the opening statements above about +15% to +30% gains in specific stocks. Those are fact-based histories of all prior real-market experiences from forecasts made before the fact, not just blown smoke over some after-the-fact single illustration of convenient history.

"Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The company offers EXONDYS 51, a disease-modifying therapy for Duchenne muscular dystrophy (DMD). Its products pipeline include Golodirsen, a product candidate that binds to exon 53 of dystrophin pre-mRNA, which results in exclusion or skipping of exon during mRNA processing in patients with genetic mutations; and Casimersen, a product candidate that uses phosphorodiamidate morpholino oligomer [PMO] chemistry and exon-skipping technology to skip exon 45 of the DMD gene. In addition, the company's pipeline comprises SRP-5051, a peptide conjugated PMO that binds to exon 51 of dystrophin pre-mRNA. It has collaboration agreements with Nationwide Children's Hospital to advance micro-dystrophin gene therapy program under the research and license option agreement; Galgt2, a gene therapy program for the treatment of DMD; and Neutrophin 3, a gene therapy program to treat Charcot-Marie-Tooth neuropathies. The company also has a license agreement with Lysogene to develop LYS-SAF302, a gene therapy for mucopolysaccharidosis IIIA; a license and option agreement with Lacerta to develop treatments for CNS-targeted and lysosomal storage diseases; and research collaboration and option agreement with Genethon to develop micro-dystrophin gene therapy products. In addition, it has a research agreement with Duke University to advance gene editing CRISPR/Cas9 technology for restoring dystrophin expression; a collaboration agreement with Summit (Oxford) Ltd. to commercialize products in Summit's utrophin modulator pipeline; a strategic collaboration with Paragon Bioservices; and a strategic collaboration with CENTOGENE for the identification of patients with DMD in the Middle East and North Africa region. Sarepta Therapeutics, Inc. was founded in 1980 and is headquartered in Cambridge, Massachusetts."

Source: Yahoo Finance

SRPT's and ARWR's recent daily price ranges over the past 6 months are shown in Figures 1 and 2, along with measures of their current forecast price up-to-down balances. Also shown are the odds of long position gains being earned in the couple of months subsequent to points in time in the past 5 years when MMs had the same kind of outlook they have today.

Figure 1

source: Author

Figure 2

source: Author

As a contrast, here is what MM forecasts for the "market-index" ETF of SPDR S&P 500 Trust (SPY) looks like at this time:

Figure 3

source: Author

How effective the MMs have been in forecasting for these stocks is a matter of market records, when conditions of uncertainty similar to today's are examined. That was done in the row of data between the graphics of Figures 1-3. For ease of comparison, they are repeated and slightly expanded in Figure 4.

Figure 4

source: Author

As explained in the prior Biotech Developer revue featuring ARWR, the SRPT Range Index [RI] of 23 produced 108 of 124 net gain %Payoffs under TERMD of +30.1%.

A comparison of the +30.1% payoffs with the present forecast of +23.1% suggests an exceptional profit achievement with a degree of credibility for the current outlook of 1.30, as indicated at column [N] of Figure 4.

So much for the "good side" of a buy proposition; what about the "bad side"?

As we condition the credibility of the upside price change forecast by comparison with actual experience, so too do we look to see how bad the downside might get. But with concern only during those "long" holding periods when committed capital would be at risk under the TERMD discipline. All other periods are irrelevant, shocking as they may be.

Figure 1's data row tells what the worst case price drawdowns have been (an average of them) during all of each actual exposure period when they were to be held. What matters is how bad a fear of loss may get induced any time, not just whether or not it existed at the end of the holding. Investors will have varied reactions to the exposures, so there is no way to evaluate potential risk impact by historic outcomes. But some useful guidance may be provided by having knowledge of the maximum degree of intensity possibly becoming present.

One logically-simplified way to address the combination of stock price risk and reward is to weight each part by its probability and combine the two. The "Win Odds" of profitable position odds here for SRPT of 108 out of 124, or 87 out of 100 offer such a probability. One minus those odds, or 100 - 87 provides the loss probability weight. Thus 0.87 times +30.1% plus 0.13 times -8.7% produces a weighted net payoff of +25.1%.

To make this style of evaluation more comparable between varied investment opportunity situations, an integration of the likely holding periods used in the calculation is helpful. For SRPT, the average number of market days required by all 129 positions of the sample was only 40 out of the maximum 63 possible, because of the high proportion of upside target prices reached.

A standard evaluation measure used in many capital planning decision situations is the expected net payoff stated in "basis points" of 1/100ths 1%, per day of capital involvement. On a 365-day calendar year +19 bp/day when sustained for a year doubles the original capital, or a CAGR of +100%. When a smaller-count of 252 market days makes up a relevant year, the fewer days are each proportionally more powerful, so only 14 bp/mkt day does the 100% equivalent.

Comparison is the essence of evaluation. If the investing objective is to make capital as productive of future spend-able amounts as possible, using an odds-weighted bp/d yardstick can be helpful.

To that end, Figure 4 includes the relevant MM forecasts and their prior outcomes for ARWR and the market-index proxy of the SPDR S&P 500 Index ETF (SPY). Also, the average of some 2,700 current-day MM price-range forecast issues, and a ranked set of the day's likely 20 best of those near-term wealth-building stocks under TERMD portfolio discipline.

All of these comparisons in Figure 4 have the same basic data as included in the row of Figure 1 for SRPT. That is expanded by the columns [O] through [R] to provide for odds-weighted bp/day price-prospect evaluation comparisons.

Competition from the market-index alternative SPY at this point in time is rather limited because of an unenthusiastic upside target outlook of only +5.5% at a CAGR of only +9% and an Odds-Weighted net prospect [Q] of +0.8%. That is better, though, than the overall population of 2,711 where MM forecasts are a modest net decline (-2.2%).

Sarepta Therapeutics, Inc. and Arrowhead Pharmaceuticals Inc. both offer outstanding prospects for capital gains with strong odds for achievement in short periods of holding. SRPT has the larger potentials, but ARWR appears historically to have quicker achievement prospects. Payoff potentials in basis points per day are exceptional. For further information, please check my blog here on Seeking Alpha.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a long position in SRPT over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Disclaimer: Peter Way and generations of the Way Family are long-term providers of perspective information, earlier helping professional investors and now individual investors, discriminate between wealth-building opportunities in individual stocks and ETFs. We do not manage money for others outside of the family but do provide pro bono consulting for a limited number of not-for-profit organizations.We firmly believe investors need to maintain skin in their game by actively initiating commitment choices of capital and time investments in their personal portfolios. So, our information presents for D-I-Y investor guidance what the arguably best-informed professional investors are thinking. Their insights, revealed through their own self-protective hedging actions, tell what they believe is most likely to happen to the prices of specific issues in coming weeks and months. Evidences of how such prior forecasts have worked out are routinely provided in the SA blog of my name.

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Sarepta Therapeutics, Inc. And Arrowhead Pharmaceuticals Now Top-Ranked Biotech Stock Buys - Seeking Alpha

A team of researchers in China have genetically engineered a pig with human DNA and transplanted skin grafts onto monkeys in a milestone they say will pave the way for future skin and organ transplantations.

In the United States alone, more than 113,000 people are awaiting organ transplants yet just over 36,000 occur each year, according to the Health Resources and Services Administration. Xenotransplantation, the process of grafting or transplanting organs or tissues between different species, may be a solution to the shortage of organs around the world and provide treatment for patients with terminal organ failure, write the researchers in bioRxiv, a pre-print server for biology that has not been certified by peer-review for publication in a journal.

Pigs are widely used in biomedical research yet they are not phylogenetically close to humans, so rejection and incompatibility can occur. Genetically modifying donor pigs to serve as a potential organ source may provide a potentially viable solution, but the necessary combinations of genetic modifications in pigs for human xenotransplantation have not yet been determined.

To test these parameters, researchers at the First Affiliated Hospital of Nanchang University in China removed key pig genes that trigger organ rejection and added eight human genes to modified pigs in order to further reduce the chance of an organ being rejected. Skin was then transplanted from the pigs to monkeys and survived up to 25 days without the monkeys requiring immunosuppressive drugs.

Genetic modification of the pig is necessary to account for the differences between the pig and human genome, especially from the immune and molecular compatibility aspects, write the authors, adding that CRISPR/Cas9 technology has accelerated this process but determining which combinations remains an open question.

The authors note that extensive genome editing in certain pig cells is not a practical endeavor because of the telomere length, which requires complex and extensive editing and a long cell culture time that may lead to cell aging or death. There is also a low risk that porcine endogenous retrovirus (PERV), a virus integrated into the genomes of pigs, could infect human hosts. Even so, the findings have great potential for clinical value to save severe and large area burn patients and other human organ failure.

As the skin is considered the vital, unique and immunogenicity organ, our preliminary success in skin xenotransplantation using the combination of multi-gene modified pig in NHP provides the approval of the concept, paves a way to initiate the other organ preclinical trial and clinical trial, implies a success of these organs xenotransplantation, writes study author Wang Gang in a comment, adding that genetically altered pigs may have the potential to become an unlimited organ source for future clinical transplantation.

The researchers add that their findings may also have applications for human disease modeling and potentially help to one day establish disease-resistant animals.

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Pigs Genetically Engineered With Human Cells May Pave The Way For Future Skin Transplants - IFLScience

Genetically altering symbiotic gut bacteria in honey bees is successful at killing varroa mites, which tend to make bees sick and leave them at an increased risk of colony collapse disorder, according to a study published today (January 31) in Science.

Colony collapse disorder (CCD) occurs when the majority of a hive abandons ship, leaving behind the queen, honey and pollen stores, and young, immature bees behind. Without the workforce of a full hive, the colony fails. According to the US Department of Agriculture, there does not appear to be a single cause of CCD, rather, it is likely a combination of disease, parasites, poor nutrition, pesticide exposure, and other stressors on the hive.

One possible contributor to unhealthy hives are Varroa destructor mites, an invasive species that arrived in North America in the early 1980s. Not only do these parasites feed on the bees fat stores, but they also transmit a virus that leads to the deformation of their wings. As a bees health declines, it becomes more susceptible to contracting other illnesses. If a hive becomes infested with these mites, it might be enough of a threat for the healthy bees to bug out, leaving their hivemates behind.

To fight back against Varroa, researchers looked to Snodgrassella alvi, a symbiotic bacterium found within the gut of honey bees. Genetic modification of the microbes enabled them to destroy the mites from the inside out through RNA interference (RNAi). The engineered bacteria produced double-stranded RNA that induced the mites to launch an RNAi defense to destroy those sequences. Because the bacterial sequences matched those from the varroa genome critical to the mites survival, the silencing mechanism wiped out the mite transcripts as well, killing the parasites

It is a bit like a customized medicine for honey bees, Jeffrey Scott, an insect toxicologist at Cornell University who was not involved with the study, tells Science. Being able to engineer a gut microbe and specifically regulate gene expression in the host has enormous implications.

By using S. alvi as a manufacturer, the team was able to provide a continued supply of the RNA, providing a useful window for the bees to fight back against the mites. The effects lasted for the duration of the 15-day-long experiment and bees with the altered bacteria were 70 percent more likely to kill mites within 10 days than those without it.

If the technique works in the field, that could be the end of Varroa and the viruses, Robert Paxton, a bee ecologist at Martin Luther University who was not involved with the study, tells Science.

While the results of this small-scale experiment are encouraging, the method wont be used in the wild anytime soon. Releasing bacteria with gene-silencing potential invariably raises containment questions along with concerns that mutations may cause unintended consequences.

Youre turning off genes [via RNAi], honeybee epidemiologist Dennis vanEngelsdorp of the University of Maryland who was not involved with the study tells Science News. There has to be a very healthy debate about how do we regulate this?

Lisa Winter is the social media editor forThe Scientist. Email her at lwinter@the-scientist.com or connect on Twitter @Lisa831.

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Engineered Microbe in Bees Guts Fends off Deadly Varroa Mite - The Scientist

It involves milking snake venom by hand and injecting it into horses or other animals in small doses to evoke an immune response. The animal's blood is drawn and purified to obtain antibodies that act against the venom.

Producing antivenom in this way can get messy, not to mention dangerous. The process is error prone, laborious and the finished serum can result in serious side effects.

Experts have long called for better ways to treat snake bites, which kill some 200 people a day.

Now -- finally -- scientists are applying stem cell research and genome mapping to this long-ignored field of research. They hope it will bring antivenom production into the 21st Century and ultimately save thousands, if not hundreds of thousands, of lives each year.

Researchers in the Netherlands have created venom-producing glands from the Cape Coral Snake and eight other snake species in the lab, using stem cells. The toxins produced by the miniature 3-D replicas of snake glands are all but identical to the snake's venom, the team announced Thursday.

"They've really moved the game on," said Nick Cammack, head of the snakebite team at UK medical research charity Wellcome. "These are massive developments because it's bringing 2020 science into a field that's been neglected."

Hans Clevers, the principal investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, never expected to be using his lab to make snake venom.

So why did he decide to culture a snake venom gland?

Clevers said it was essentially a whim of three PhD students working in his lab who'd grown bored of reproducing mouse and human kidneys, livers and guts. "I think they sat down and asked themselves what is the most iconic animal we can culture? Not human or mouse. They said it's got to be the snake. The snake venom gland."

"They assumed that snakes would have stem cells the same way mice and humans have stems cells but nobody had ever investigated this," said Clevers.

After sourcing some fertilized snake eggs from a dealer, the researchers found they were able to take a tiny chunk of snake tissue, containing stem cells, and nurture it in a dish with the same growth factor they used for human organoids -- albeit at a lower temperature -- to create the venom glands. And they found that these snake organoids -- tiny balls just one millimeter wide -- produced the same toxins as the snake venom.

The team compared their lab-made venom with the real thing at the genetic level and in terms of function, finding that muscle cells stopped firing when exposed to their synthetic venom.

The current antivenoms available to us, produced in horses not humans, trigger relatively high rates of adverse reactions, which can be mild, like rash and itch, or more serious, like anaphylaxis. It's also expensive stuff. Wellcome estimate that one vial of antivenom costs $160, and a full course usually requires multiple vials.

Even if the people who need it can afford it -- most snakebite victims live in rural Asia and Africa -- the world has less than half of the antivenom stock it needs, according to Wellcome. Plus antivenoms have been developed for only around 60% of the world's venomous snakes.

In this context, the new research could have far-reaching consequences, allowing scientists to create a biobank of snake gland organoids from the 600 or so venomous snake species that could be used to produce limitless amounts of snake venom in a lab, said Clevers.

"The next step is to take all that knowledge and start investigating new antivenoms that take a more molecular approach," said Clevers.

To create an antivenom, genetic information and organoid technology could be used to make the specific venom components that cause the most harm -- and from them produce monoclonal antibodies, which mimic the body's immune system, to fight the venom, a method already used in immunotherapy treatments for cancer and other diseases.

"It's a great new way to work with venom in terms of developing new treatments and developing antivenom. Snakes are very difficult to look after," Cammack said, who was not involved with the research.

Clevers said his lab now plans to make venom gland organoids from the world's 50 most venomous animals and they will share this biobank with researchers worldwide. At the moment, Clevers said they are able to produce the organoids at a rate of one a week.

But producing antivenom is not an area that pharmaceutical companies have traditionally been keen to invest in, Clevers said

Campaigners often describe snakebites as a hidden health crisis, with snakebites killing more people than prostrate cancer and cholera worldwide, Cammack said.

"There's no money in the countries that suffer. Don't underestimate how many people die. Sharks kill about 20 per year. Snakes kill 100,000 or 150,000," said Clevers.

"I'm a cancer researcher essentially and I am appalled by the difference in investment in cancer research and this research."

One challenge to making synthetic antivenom is the sheer complexity of how a snake disables its prey. Its venom contains several different components that have different effects.

Researchers in India have sequenced the genome of the Indian Cobra, in an attempt to decode the venom.

"It's the first time a very medically important snake has been mapped in such detail," said Somasekar Seshagiri, president of SciGenom Research Foundation, a nonprofit research center in India.

"It creates the blueprint of the snake and helps us get the information from the venom glands." Next, his team will map the genomes of the saw-scaled viper, the common krait and the Russell's viper -- the rest of India's "big four." This could help make antivenom from the glands as it will be easier to identify the right proteins.

In tandem, both breakthroughs will also make it easier to discover whether some of the potent molecules contained in snake venom are themselves worth prospecting as drugs -- allowing snakes to make their mark on human health in a different way to how nature intended -- by saving lives.

"As well as being scary, venom is amazingly useful," Seshagari said.

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Snake venom can now be made in a lab and that could save many lives - CNN