Written by Armaan Abraham, Arek Der-Sarkissian, and George BandekA recent breakthrough at Stanford University could change the future of dermatology and medicine at large. Currently, in order to identify skin cancer, a doctor’s report is required of an examination of the mole, without the use of any equipment. A dermatologist would then use a microscope or such magnifying equipment to better examine the mole and make a diagnosis. In a means of better facilitating this process, Stanford has developed an app where users can submit images of moles that, through the use of artificial intelligence, would be classified as one of two categories: malignant or benign. The essence of this app is built on the fact that developers can teach a system to recognize cancer through the use of thousands of training images that have already been classified as one of the categories. This system would have the ability to constantly improve its performance by incorporating images and respective diagnoses from past users. Beyond its actual use, the existence of an application that tests suspected moles and provides a “preliminary diagnosis” may result in numerous benefits to the medical field.
As previously discussed, the Stanford study makes use of a technique that falls under the broad field of machine learning. Machine learning is the process of teaching a computer, or a model, how to identify and comprehend patterns in data in order to do something useful with it. In this case, the researchers at Stanford used image data of moles and the diagnoses associated with each respective image in order to train a convolutional neural network (CNN) how to identify characteristics of a mole and whether it is cancerous. CNN’s are a type of machine learning architecture that has seen outstanding success in image classification in recent years. It excels at identifying spatial dependencies and patterns that ultimately determine what makes, say, a mole look like a mole. The results were surprisingly promising; the algorithm was as accurate in its diagnoses as a certified dermatologist. A dermatologist’s ability to recognize cancerous moles comes from their knowledge of what different categories of moles look like. Machine learning simulates that process by using data fed to the algorithm, which is why it works so effectively in this situation. The algorithm itself is based on one of Google’s machine learning algorithms. Google’s algorithm originally recognized images of everyday objects, and it took millions of images of each kind as training data. The researchers at Stanford took the base code and instead trained it on images of moles. Given the numerous applications of machine learning, deep learning, and artificial intelligence both inside and outside of medicine, it is evident that the potential of these technologies is enormous. Another machine learning algorithm, different than the one applied in the Stanford mole study, could be used by physicians to monitor the daily routines of patients. The algorithm could detect abnormalities in routines and translate them to potential health problems a patient could be experiencing. Those abnormalities could trigger various safety mechanisms. For example, emergency services could be dispatched if an individual hasn’t kept to their normal routines for a few days. When presented with repetitive data sets, an automated system is always quicker. Lives can be saved by having ML models do this work. We’re excited for the success of the mole study’s algorithm, and look forward to seeing the future of machine learning and deep learning in medicine. https://medium.com/@bruinmedicalentrepreneurs/machine-learning-with-moles-c340d0ea2403
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Written by Kaushal Rao, Crystal Song, and Patrick HofbauerAlzheimer’s disease (AD) is a neurodegenerative disorder that contributes to the deterioration of the cognitive abilities of afflicted patients, and is the leading cause of dementia among older adults. There have been many copiously funded research efforts over the years, but there are still a limited number of available therapies. Could the next breakthrough lie in seaweed?
In late 2019, Shanghai’s Green Valley Pharmaceuticals (GVP) developed a new drug called oligomannate, which has been conditionally approved by China’s National Medical Products Administration (NMPA) and deemed fit for treating individuals with mild to moderate forms of AD. Oligomannate is the only approved AD drug anywhere in the world since Namenda’s approval 17 years ago. According to South China Morning Post, the drug was made available everywhere throughout China by the end of 2019. Estimates vary, but experts at Alzheimer’s Disease International have suggested that as many as 50 million individuals around the world live with AD. The market for AD therapeutics is estimated to reach around $14.8 billion by 2026, according to GlobalData. Despite the financial incentive to develop effective therapies, the history of research into AD therapeutics has been filled with setbacks. Between 1998 to 2017, 146 potential medicines proved unsuccessful in clinical trials, and only four medicines received approval from the Food and Drug Administration (FDA). However, these approved medicines only manage symptoms and are unable to actually slow the disease’s progression. Progress in AD research is sluggish because of three key factors: 1) Identifying eligible patients for clinical trials is a big challenge, 2) AD is difficult to diagnose early (which ties into identifying candidates for clinical trials), and 3) The biological pathway of AD is not yet fully understood. Although these three factors will continue to play a large role in hindering AD research, modern technological advancements have helped researchers develop newer types of drugs, such as tau-based and amyloid therapeutics. Oligomannate’s approval in 2019 marked the long-awaited addition of therapy options for AD. The news brought some hope to the millions of individuals and families suffering from the disease. Many translational scientists found the news fascinating as well, especially as oligomannate was the only approved AD drug in 17 years. Over the past years, scientists have been focusing on directly attacking the beta-amyloid plaques that are thought to interfere with neural signaling in AD patients’ brains, but 99% of these therapies have failed in clinical trials. Oligomannate’s claimed successes in animal models and human trials proposed a novel strategy to treat AD through the gut microbiome, introducing a new perspective. The seaweed-derived drug is said to reduce neuroinflammation, as well as inhibit AD progression, by remodelling the patient’s gut microbiota and suppressing gut bacterial amino acid production. The mechanistic link between gut dysbiosis and AD is not yet completely proven, but several biological pathways have been proposed to explain the link. One of the more commonly accepted theories involves the accumulation of certain amino acids in the gut and the resulting proliferation of pro-inflammatory cells. These cells infiltrate the brain and contribute to AD-associated neuroinflammation. This neuroinflammation is in turn associated with the development of amyloid plaques and tau tangles, the primary physiological symptoms of the disease. By resolving this amino acid imbalance, oligomannate is hypothesized to ultimately hinder the development of plaques and tangles. At first glance, oligomannate seems like an incredible breakthrough. In its Phase III clinical trial, oligomannate had a treatment result comparable to that of the approved drug Namenda — the current standard of care drug for AD patients. However, much skepticism regarding oligomannate’s efficacy has also arisen due to the drug’s rather unusual clinical trial data. Oligomannate’s Phase IIb clinical trial was conducted in 2013 and 2014 in a cohort of 255 patients. Surprisingly, that trial was deemed a failure because the difference in cognitive function between treatment and placebo groups was not found to be statistically significant. Hence, the fact that the company continued oligomannate’s trials into Phase III was already a questionable decision. In addition, peer reviewers have been doubting the abnormal placebo data points in oligomannate’s Phase III clinical trial. As shown in the figure, the placebo group, along with the treatment group, experienced an improvement in cognitive function over the first 24 weeks of study. However, in the last 12 weeks, the placebo group’s cognitive function drastically decreased, which led to oligomannate’s “successful” clinical trial outcome. Interestingly, the company has not given any clear explanation for the bizarre trend in placebo data. As of March 2020, Green Valley Pharma has announced that they are planning to test the GV-971 compound in 200 clinical centers across Europe, North America and in certain parts of Asia. The plan is to complete these global clinical trials by 2024 and then submit GV-971 for potential approval to the FDA and EMA in 2025. However, much doubt remains regarding the true efficacy of the marine-algae-derived drug. If these trials demonstrate that GV-971 truly has therapeutic potential, then many patients will be in luck. However, given the current scientific uncertainty, it would be wise to temper any irrational exuberance with the appropriate dose of scientific skepticism. https://medium.com/@bruinmedicalentrepreneurs/too-good-to-be-true-seaweed-derived-alzheimers-therapeutic-shows-potential-ca8932fd800d Written by Suraj Doshi and Varun PatroVertex is a leading biotech company steadily becoming recognized for its progress in treating Cystic Fibrosis (CF), an inherited disease in which patients’ lungs are clogged by mucus, obstructing air flow. Vertex has launched 4 CF drugs in the past 8 years, with its most recent launch, Trikafta, promising to have the most widely-felt impact. Compared to the company’s previous launch Kalydeco, which could only help 4% of CF patients in the United States, Trikafta is projected to treat nearly 90% of CF patients. Vincent Donato, a CF patient who had been treated by Orkambi and Symdeko, two earlier CF drugs launched by Vertex, experienced debilitating side-effects from both drugs while seeing only marginal improvements to his CF. Trikafta, however, proved to be the solution he needed. Donato says “There are no words to describe the feeling of taking deep breaths and having it travel through your entire body. My cough was quickly subsiding as I began coughing up white, clear, saliva-looking mucus.”
Trikafta is the culmination of nearly 8 years of CF research, a one-pill combination of the company’s 3 earlier CF drugs. Two of these drugs, Orkambi and Symdeko were themselves two-drug combinations that drastically increased the therapeutic potential relative to Kalydeco in 2013. After this success, the company made a massive push for their most recent launch, combining 3 drugs and reaching approval in 3 years, nearly a fifth of the time it would typically take a biotech company to develop a new medicine. Reshma Kewalramani, Vertex’s current CEO and then Chief Medical Officer says “The incredible speed of this approval underscores our shared sense of urgency with the FDA and the CF community for bringing this medicine to eligible people with CF, particularly those without a medicine targeting the underlying cause of their disease.” Looking to the economic spectrum, the profit margins that Trikafta has brought Vertex are astronomical. After the initial launch in October, the company’s stock shot up nearly 70 points (from 170 to 240) in 4 months. From their previous two CF drugs, Orkambi and Symdeco, Vertex was able to bring in over 3 billion dollars in revenue. After the release of Trikafta, this figure rose by roughly 700 million dollars and is predicted to continue to rise. Trikafta alone is forecasted to bring in a profit margin of 1.2 billion dollars this year and this profit margin is predicted to increase by 30% annually. Marvelous as Vertex’s drug is, affordability is an entirely different issue. Stat Magazine predicts that the drug will cost approximately $311,000 per patient, an imposing bill Vertex hopes would be footed by insurance companies. In perspective, even for financially well-off families, this number is a significant dent in their bank account. The financial impact of this drug is comparable to that of a family sending 2 of its children to public universities for the entirety of their undergraduate education. For middle and lower class Americans, it’s difficult to celebrate such groundbreaking achievements in CF treatment if you’re fully aware that financial barriers make them nearly irrelevant to your life. Oftentimes, novel medications with tremendous potential to help patients across the country are completely out of reach for a large percentage of the targeted population solely due to the price tag. While a drug company needs to meet a certain revenue quota to continue to fund their research, the profit numbers they target ensure that drug prices for patients remain obscenely high. Furthermore, the US seems to be especially criminal in this regard. After all, European companies are selling their citizens comparable drugs for approximately half the cost. Our current trend of steadily increasing drug prices takes us in the wrong direction if our goal as a society is to make medicine more affordable. In a world where American biotech companies claim they exist to help people, we need to ask ourselves whether or not the massive profit margins they “need” are actually necessary. https://medium.com/@bruinmedicalentrepreneurs/a-game-changer-how-vertex-delivered-on-cystic-fibrosis-4a8f34a4cc1 Written by Sophia Fox, Daron Assatoury, and Bilal HamidIf you haven’t heard of synthetic biology yet, you soon will. The field of synthetic biology is centered around genetically modifying organisms (plants, bacteria, fungi, etc) to perform new abilities, such as producing proteins or biofuels. The applications are endless, especially within the realm of regenerative medicine. Taking the field by storm is revolutionary Israeli company CollPlant, which has successfully engineered tobacco plants to produce recombinant human collagen (rhCollagen).
Human collagen is a critical component of structural support in many organs and tissues, and the variant which CollPlant’s genetically modified tobacco plants produce is identical to humans’ type I collagen. rhCollagen is superior to collagen harvested from animals due to its ‘improved biofunctionality, high homogeneity, and reduced risk of immune response’, as CollPlant’s website describes. Animal-extracted collagen has reduced functionality since it contains partially denatured cell binding sites and is viewed as a foreign body by the immune system. rhCollagen avoids these problems and can be used for faster cell proliferation and cell repair for tissue healing. The primary use of rhCollagen is as scaffolding for tissue regeneration. This has applications in wound healing, 3D bioprinting structure for organs and tissues, and medical aesthetics. There are various mechanisms by which rhCollagen can provide this framework, including Collplant’s rhCollagen-based ‘BioInk’, which can be used for 3D bioprinting. It is important to note that rhCollagen does not heal in itself, but rather provides the framework for which other cells can more effectively and efficiently heal the tissues. Currently, biosynthetic collagen is already being used to accelerate the recovery period of individuals afflicted with persisting physical ailments, such as chronic “tennis elbow,” which has about a 1–3% prevalence rate in the mature population. By implementing rhCollagen into its serum, Vergenix enables the body to construct a scaffold for which to rebuild tissue and enhance clotting ability. After this scaffold is created and an extracellular matrix is established, the collagen degrades and exits the body over time. A study published by CollPlant involving adults with long-lasting lateral elbow pain has shown that the injection of Vergenix STR, a product of CollPlant’s synthesized rhCollagen, can reduce patient-reported pain incidence by 59% 6 months into the treatment through the enabling of quicker regeneration of bodily tissue. Furthermore, about 68% of patients had a statistically significant increase in grip strength at the same point in time. Ultrasound tests further concluded that the synthesized collagen had actively promoted recovery. The application of plant-based rhCollagen[1] is not limited to wounds and bruises: the company is planning to branch out into the cosmetic field,[2] specifically dermal fillers and breast implants. By utilizing plant-synthesized human collagen, CollPlant can usher in a new, more natural wave of plastic surgery that may prove to be both safer and more effective. In addition, post surgical costs could be greatly reduced due to decreased chances of rejection and immune response. CollPlant is the single provider for Type 1 human collagen through recombinant technology. In this position, changes in investment[3] relevant to CollPlant are representative of the market as a whole. With both life-saving and aesthetic applications, the development of synthetic collagen provides a significant alternative to many current methods. In deviating from animal procurement, CollPlant opens up a wider market of consumers who wish to undergo enhancements, but who are weary of the health risks or the idea that collagen is normally derived from animals. Supported by recent statistics, there exists a growing belief in the viability and profitability of providing alternative collagen solutions in today’s market. The recent acquisition of $5.5 million in financing by CollPlant supports the development of new R&D facilities as well as a production facility equipped to handle the greater demand of CollPlant’s product from bioprinting. In addition to the expansion of their facilities, the Israel-based company secured over 80% of recent financing from U.S. based investors with significant experience in the medical field and bioprinting fields. This displays an important increase in investor confidence in the ability of CollPlant to play an important role in the US medical technology market as well as expands its ability to connect with US firms and push the development of recombinant collagen production. Through recent agreements with United Therapeutics, CollPlant is already displaying growth into the market as they codevelop scaffolding using their recombinant collagen in order to develop synthetic lungs. Successful R&D in this field opens up a huge market for recombinant collagen by breaking down one of the key barriers to 3D organ printing and synthetic organ manufacturing. Since recombinant collagen does not elicit an immune response, these synthetic organs can dramatically decrease the cost of post-transplant care by virtually eliminating the need for immunosuppressants. As the technology improves, a future where wounds are a matter of administering a patch of synthetic collagen may be nearer than we imagine. The results are quite promising: all that’s left to do is make sure a sizeable dose won’t break the bank, and we will be one step closer towards a wear-and-tear free society. https://medium.com/@bruinmedicalentrepreneurs/the-tobacco-plant-that-could-cure-your-wounds-new-applications-of-synthetic-biology-c8025cccb7e7 Written by Aayush Patel and Shashank VenkatThe Butterfly iQ received the Fast Company’s 2019 World Changing Idea Awards in the Health category for its ability to produce diagnostic imaging in the palm of one’s hands. Machinery such as MRI, PET scans, and ultrasounds are now accessible to people all over the world with this piece of biotechnology.
With the Butterfly iQ being compatible with individuals’ mobile phones, this portable device has cut costs immensely, as diagnostic imaging technology can cost anywhere from $10,000 to $200,000 for medical practices to purchase. However, the $2,000 Butterfly iQ has become practical due to the shrinking of its technology. Instead of the use of quartz crystals to transfer the sound waves into one’s body, the Butterfly iQ utilizes thousands of metal drums fit on a single silicon chip. These images can then be viewed using the mobile app. Jonathan Rothberg, founder of the Butterfly iQ and a doctor himself, holds this invention quite close to him as his daughter was diagnosed with tuberous sclerosis. His intention of making the difficult medical imaging technology to be more convenient for individuals also suffering from various medical issues has the potential to positively impact those who cannot afford to get treated with this intensive technology. We feel that the United States also serves to gain a lot from the introduction of this technology as it already has the potential to provide an affordable option in the eyes of third world countries. Some potential benefits that could result from this technology include patients getting faster diagnoses to any medical problems that rely on medical imaging technology. While the older, much larger machines may require a few trips to the hospital from the patient in order to get a clear diagnosis, the Butterfly iQ allows for doctors to quickly check what the patient is suffering from — clearly making hospitals much more efficient at helping patients. Furthermore, the cost of Butterfly iQ is obviously a benefit for third world countries, as mentioned before, but this low-cost will help how fast it can get to hospitals throughout the United States. With its price of $2000 at half of the current lowest portable device price of $4000, and also a tenth of most non-portable medical imaging technology, Butterfly iQ is on its path to get to all hospitals looking for more efficient technologies. There’s clear evidence of this: just last fall, this company began to send out shipments to more than 20,000 medical professionals who had already placed orders. Notable investors have taken an interest in this technology as well with organizations like the Bill and Melinda Gates foundation putting in a total investment of about $250 million. Clearly, the Butterfly iQ has caused a huge decrease in cost and an increase efficiency, comparable to a piece of biotechnology called the Oxford minION, a $1000 DNA sequencer that can be connected via USB to a computer. Like the Butterfly iQ, the Oxford minION caused a huge leap in its respective subfield of biotechnology. https://medium.com/@bruinmedicalentrepreneurs/the-butterfly-iq-the-portable-ultrasound-machine-flying-into-the-future-2e586001b9a9 Written by Akash Gopal, Gurvardaan Bal, and Jacob MatiyevskyFor more than three decades, the stent — a thin scaffolding implanted into a blood vessel to keep it from closing in on itself through an invasive surgical procedure — has been used to treat people with heart disease. Recently, however, new research has shown that stents, and invasive bypass surgery in general, may be unnecessary even for patients with severe heart disease. as long as This new information challenges medical dogma that has stood since the stent was first used successfully in 1986.
According to a Washington Post article, about 500,000 stents are implanted every year, but a quarter of them are given to patients without any chest pain at all. Indeed, the massive and federally funded International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) showed that stents are effective in reducing pain, but are often not worth the surgical procedure that comes with them, especially when less invasive methods offer the same lasting results in preventing heart disease from recurring. The study points out that the common, early invasive method of inserting stents does not protect patients against death or lower the overall chance of having a heart attack. The researchers suggest that these methods should in fact, be used more sparingly and replaced by drugs that can accomplish the desired goal. In fact, a market already exists for a pill that is perhaps more effective in reducing pain, making the decision to opt-out of invasive surgery even easier for patients. This study should serve as strong motivation for the medical industry to begin transitioning away from stent technology and over to something that does a better job at reducing a patient’s pain while lowering the risk of complications. Such a large transition in the medical field is made difficult, however, with the role played by doctors’ own emotional beliefs. Many practitioners have been working for decades with a particular method which they’ve come to trust and rely upon, and changing their minds isn’t something that can happen suddenly. Among all alternatives that exist for stent treatments, there are two primary options: those which are invasive and those which are non-invasive. Despite it being better to stick to non-invasive options, it is worth noting what the exact problems are with stents. Not only do they not prevent fatality from occurring, there is also potential for arteries to re-narrow on top of the stent, which is called restenosis. In order to combat this, drug-eluting stents were recently developed and used to prevent it from happening. However, these stents have the potential to form clots inside the stent itself, which can be fatal. From this, we can see that the issue with the stent design primarily comes from the design itself. With this in mind, we can also consider other invasive options that may be more effective than the stent. In terms of invasive options, we are only considering options that do not require any tissue transplantation. For that reason, heart transplants, cardiomyoplasty, and similar methods will not be considered. The remaining methods focus on removing plaque that is clogging an artery, or in other words methods that do not require any pieces to stay inside the heart. Laser angioplasty involves the use of a catheter with a laser attached to its tip to open the artery. Light beams are then used to vaporize build-up of plaque. In atherectomy, the same general procedure is used, but instead of a laser, a shaver is used to cut away the plaque and collect it. For non invasive options, there are drug options including but not limited to Plavix, Effient, and Brilinta. These drugs are antiplatelets which prevent the formation of clots inside arteries. To actually remove plaque, there are some drugs called statins which can accomplish the task. Statins work to lower cholesterol levels in the body, so they can help reduce chances of serious injury or death from heart conditions by 25–35%. When deciding between alternatives, the effectiveness of either choice ultimately depends on the individual. There certainly are risks to consider with invasive options due to their nature, but drug options can also have side effects that should not be taken lightly. Studies have proven time and time again, however, that these less invasive measures can accomplish many of the same results as their more invasive analogs. This simple truth, when combined with the knowledge that invasive procedures like stent implantation carry the manifold potential errors associated with any surgical procedure, makes it clear that drugs like Plavix and Brilinta should be the preferred default when treating heart disease. https://medium.com/@bruinmedicalentrepreneurs/emerging-alternatives-to-stents-ed24c07d7bc2 |