Discover all the latest about our products, technology, and Target Health culture on our official blog.
September 9, 2020Target Healthy Eating
1/2 cup honey (your choice)
1/2 teaspoon turmeric
2 pinches chili flakes (more or less, to your taste)
1 teaspoon extra virgin olive oil
2 garlic cloves
1 anchovy fillet
Candied Pecans (or walnuts)
1/4 cup granulated sugar
2/3 cup toasted pecans or walnuts (you toast them)
Pinch black pepper
Pinch salt (optional)
3 medium peaches, washed, dried, then sliced
3/4 cup fresh basil leaves
Burrata (only burrata) - 4 ounces
Fresh mint leaves for garnish
Extra virgin olive oil at table (optional)
I've been obsessed with Bel Canto opera this week. Either ignore these, or join me with three of the most exquisite duets ever written. Music has helped us get through the Spring and Summer of 2020.
You can carry on, the torch of peace and brotherhood and simply live by the Golden Rule!
From Our Table to Yours
Have a Great Week Everyone!
September 9, 2020Regulatory
Patients with Type 1 diabetes, or their caregivers, must consistently monitor their glucose levels throughout the day and inject insulin with a syringe, pen or pump to maintain adequate glucose levels in order to avoid becoming hyperglycemic (high glucose levels) or hypoglycemic (low glucose levels).
The FDA has approved the MiniMed 770G System, a hybrid closed loop diabetes management device that is intended to automatically monitor glucose (sugar) and provide appropriate basal insulin doses with little or no input from the users or their caregivers for use by individuals aged 2 to 6 with type 1 diabetes. The 770G System is a first-of-a-kind device for patients aged 2 to 6 years. It is the first legally marketed device that can automatically adjust insulin delivery based on continuous glucose monitor values for this patient population.
The MiniMed 770G System, a bluetooth-enabled version of the previously approved MiniMed 670G System (with other modifications), is a hybrid closed loop system that works by measuring glucose levels in the body every five minutes and automatically adjusting insulin delivery by either administering or withholding insulin. The system includes: a sensor that attaches to the body to measure glucose levels under the skin; an insulin pump strapped to the body; and an infusion patch connected to the pump with a catheter that delivers insulin. While the device automatically adjusts insulin levels, users need to manually request insulin doses to counter carbohydrate consumption at mealtime.
The FDA evaluated data from a clinical trial that included 46 children aged 2 to 6 years old with type 1 diabetes. Study participants wore the device for approximately three months to evaluate the performance of the device during both the at-home periods, as well as a hotel period, to stress the system with sustained daily exercise. That study found no serious adverse events and that the device is safe for use. Data from that study was used to help support the expanded indication for patients 2 to 6 years old.
Risks associated with use of the system may include hypoglycemia, hyperglycemia, as well as skin irritation or redness around the device's infusion patch. As part of this approval, the FDA is requiring the device manufacturer to conduct a post-market study to evaluate device performance in real-world settings in children between the ages of 2 and 6. This device is not approved for use in children younger than 2 years old and in individuals who require less than eight units of insulin per day.
The approval of the MiniMed 770G hybrid closed loop system was granted to Medtronic.
September 9, 2020COVID-19
According to a paper out of the Intellectual and Developmental Disabilities Research Centers (IDDRC) Network, and published in the American Journal of Psychiatry (28 August 2020), the COVID-19 pandemic has taken a disproportionate toll on people with intellectual and developmental disabilities (IDDs)
A large number of people with IDD who require in-person care have lost the support of trained caregivers and community service providers due to the pandemic. The authors note that the Centers for Disease Control and Prevention and others have issued guidelines for group homes, schools, and others entrusted with the care of people with IDD. According to the authors, it is vital to ensure that when they return to work, care staff exercise techniques and procedures to protect their clients from infection. Moreover, people with IDD depend on caregivers and loved ones to help them bridge gaps in intellectual and communication abilities. In the absence of this human contact, the authors call for virtual care and support, where viable. Those who cannot benefit from screen-based supports should be prioritized to receive in-person services.
Suspension of classroom time also disproportionately affects children with IDD, who often require special educational services, increased teacher-student ratios, and specialized interventions, many of which need to be administered in person. It is difficult for families to take on these tasks, and qualified in-home surrogates should be mobilized whenever possible to meet this need and to support parents' efforts. Also, people with IDD often cannot verbalize their symptoms during telemedicine appointments, and physicians need to use their best judgement in providing in-person care for them when necessary, according to the authors. The article emphasizes that people with IDD who are infected with COVID-19 should receive equal access to testing and appropriate medical care.
September 9, 2020Basic Biology
The New Guinea singing dog was first studied in 1897, and became known for their unique and characteristic vocalization, able to make pleasing and harmonic sounds with tonal quality. Only 200-300 captive New Guinea singing dogs exist in conservation centers, with none seen in the wild since the 1970s. However, the New Guinea singing dog, thought to be extinct for 50 years, still thrives and still stealthily wanders in the Highlands of New Guinea.
In a study published in PNAS (31 August 2020), using conservation biology and genomics, it was discovered that New Guinea singing dog population is opening new doors that can teach biologists about human vocal learning, and can be utilized as a valuable and unique animal model for studying how human vocal disorders arise and finding potential treatment opportunities.
According to the authors, a large amount of inbreeding within captive New Guinea singing dogs changed their genomic makeup by reducing the variation in the group's DNA. Such inbreeding is why the captive New Guinea singing dogs have most likely lost a large number of genomic variants that existed in their wild counterparts. This lack of genomic variation threatens the survival of captive New Guinea singing dogs. Their origins, until recently, had remained a mystery. Another New Guinea dog breed found in the wild, called the Highland Wild Dog, has a strikingly similar physical appearance to the New Guinea singing dogs. Considered to be the rarest and most ancient dog-like animal in existence, Highland Wild Dogs are even older than the New Guinea singing dogs.
It was previously hypothesized that the Highland Wild Dog might be the predecessor to captive New Guinea singing dogs, but the reclusive nature of the Highland Wild Dog and lack of genomic information made it difficult to test the theory. In 2016, in collaboration with the University of Papua, the New Guinea Highland Wild Dog Foundation led an expedition to Puncak Jaya, a mountain summit in Papua, Indonesia. They reported 15 Highland Wild Dogs near the Grasberg Mine, the largest gold mine in the world. A follow-up field study in 2018 allowed for the collection of blood samples from three Highland Wild Dogs in their natural environment as well as demographic, physiological and behavioral data.
According to the authors, the New Guinea singing dogs and the Highland Wild Dogs do not have identical genomes because of their physical separation for several decades and due to the inbreeding among captive New Guinea singing dogs -- not because they are different breeds. In fact, it has been suggested that the vast genomic similarities between the New Guinea singing dogs and the Highland Wild Dogs indicate that Highland Wild Dogs are the wild and original New Guinea singing dog population. Hence, despite different names, they are, in essence, the same breed, proving that the original New Guinea singing dog population are not extinct in the wild.
The authors believe that because the Highland Wild Dogs contain genome sequences that were lost in the captive New Guinea singing dogs, breeding some of the Highland Wild Dogs with the New Guinea singing dogs in conservation centers will help generate a true New Guinea singing dogs population. In doing so, conservation biologists may be able to help preserve the original breed by expanding the numbers of New Guinea singing dogs.
Although New Guinea singing dogs and Highland Wild Dogs are a part of the dog species Canis lupus familiaris, it was found that each contain genomic variants across their genomes that do not exist in other dogs that we know today.
The authors also aim to study New Guinea singing dogs in greater detail to learn more about the genomics underlying vocalization (a field that, to date, heavily relies on birdsong data). Since humans are biologically closer to dogs than birds, by studying the New Guinea singing dogs, it is hoped to gain a more accurate insight into how vocalization and its deficits occur, and the genomic underpinnings that could lead to future treatments for human patients.
September 9, 2020History of Medicine
From the 1880s to the antibiotic era, convalescent blood products (CBP) were used to prevent and treat many bacterial and viral infections in humans and in animal models. In 1890, the first rational approach exploited by the physiologists von Behring and Kitasato to treat diphtheria was blood serum; initially, it was produced from immunized animals but soon whole blood or serum from recovered donors with a specific humoral immunity were identified as a possible source of specific antibodies of human origin. There are several examples of the use of CBP for the prophylaxis or treatment of bacterial infectious diseases such as scarlet fever in the 1920-40s and pertussis until the 1970s.
Emil Behring (1854-1917) had pioneered the technique, using guinea pigs to produce serum. Based on his observation that people who survived infection with the diphtheria bacterium never became infected again, he discovered that the body continually produces an antitoxin, which prevents survivors of infections from being infected again with the same agent. It was necessary for Behring to immunize larger animals in order to produce enough serum to protect humans, because the amount of antiserum produced by guinea pigs was too little to be practical. Horses proved to be the best serum producer, as the serum of other large animals is not concentrated enough, and horses were not believed to carry any diseases that could be transferred to humans.
Due to the First World War, a large number of horses were needed for military purposes. It was difficult for Behring to find enough German horses for his serum facility. He chose to obtain horses from Eastern European countries, mostly Hungary and Poland. Because of Behring's limited financial resources, most horses he selected had been intended for slaughter; however, the usefulness of the animal to others had no influence on the production of serum. Serum horses were calm, well-mannered, and in good health. Age, breed, height, and color were irrelevant.
Horses were transported from Poland or Hungary to the Behring facilities in Marburg, in the west-central part of Germany. Most of the horses were transported by rail and treated like any other freight load. Once the horses arrived in Marburg, they had three to four weeks to recover in a quarantine facility, where data on them was recorded. They had to be in perfect medical condition for the immunization, and the quarantine facility ensured that they were free of microbes which could infect the other horses. In the Behring facilities, the horses were viewed as life savers; therefore, they were well treated. A few of the individual horses used for serum production were named, and celebrated for their service to medicine, both human and non-human.
At the end of the 19th century, every second child in Germany was infected with diphtheria, the most frequent cause of death in children up to 15 years. In 1891 Emil Behring saved the life of a young girl with diphtheria by injecting antiserum for the first time in history. Serum horses proved to be saviors of diphtheria-infected people. Subsequently, treatment of tetanus, rabies, and snake venom developed, and proactive protective vaccination against diphtheria and other microbial diseases began.
In 1901, Behring won the first Nobel Prize in Medicine for his work in the study of diphtheria.
Studies conducted during the Spanish influenza pandemic of 1918 to 1920 suggested that the use of CBP might be effective and for the first time CP was identified as a potential therapy for a number of viral infections. In the following decades, possible therapeutic efficacy was claimed for the management of measles, Argentine hemorrhagic fever, influenza, chickenpox, infections by cytomegalovirus, parvovirus B19 and, more recently, Middle East respiratory syndrome coronavirus (MERS-CoV), H1N1 and H5N1 avian flu, and severe acute respiratory infections (SARI) viruses. Furthermore, animal models of influenza pneumonia have shown the benefit of CS (protection against H1 and H3 challenge), equine hyperimmune F(ab') globulin (protection against H5N1 challenge), and monoclonal antibodies (against H1, H3, and H5N1 challenge). Interestingly, hospitalized patients with Lassa fever were also reported to have an apparently better outcome after CP administration. Furthermore, a meta-analysis on Spanish influenza-CBP (involving 8 suitable studies for a total of 1,703 patients) showed a significantly reduced mortality risk in the treated patients and suggested that CBP could be evaluated in the treatment of H5N1-related diseases.
A 2015 systematic review and exploratory post-hoc meta-analysis by Mair-Jenkins et al. on the effectiveness of CP and hyperimmune Ig for the treatment of SARI of viral etiology reported a statistically significant reduction (75%) in the odds of mortality among SARI-affected patients who were treated in comparison to those who received a placebo or no therapy. Analyses showed consistent evidence for a reduction in mortality, especially with early CP administration. However, as studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias, the authors claimed that this therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including the treatment of MERS-CoV infection.
As far as concerns CBP in the treatment of hemorrhagic fevers, in 1976 CP was used for a young woman infected with EBOV (Ebola as we know it now) in the Democratic Republic of Congo. The woman was treated, without benefits, with plasma from a person who had survived an infection with the closely related Marburg virus. During the same outbreak, 201 units of CP containing anti-EBOV antibodies (titre of at least 1:64) were obtained and frozen. Two units were transfused to an infected laboratory worker and the subject's recovery suggested the possible therapeutic effect of CP for EBOV patients.
CP was also used to treat patients with Argentine hemorrhagic fever caused by the Junin virus. In a double-blind trial carried out in 1979, patients treated with CP had a lower mortality rate compared to subjects treated with normal plasma. An analysis of 23 consecutive annual epidemics of Argentine hemorrhagic fever in a group of 4,433 patients, observed from 1959 to 1983, showed a significant difference in overall mortality between patients managed with conventional treatment or CP (42.85% vs 3.29%). Immunotherapy was also attempted through the passive transfer of immunity with CP from patients who had recovered from Crimean Congo hemorrhagic fever, but the efficacy of this treatment for this disease is still not clear.
Since the first EBOV outbreak in Congo, passive immunization in infected animals (e.g. monkeys) has been obtained with the administration of IgG preparations from horses hyper-vaccinated with EBOV thus suggesting a potential use in humans. In a 1995 outbreak in Kikwit, Zaire, eight patients received 150-400 mL of CWB and seven survived, for a mortality rate of 12.5% in comparison to 80% in untreated patients. However, give the small number of treated patients and the lack of control subjects, the authors recognized the high risk of their work not being representative and involving confounding issues. In 2007, Oswald and colleagues reported a failure of passive transfer to protect macaques against challenge with EBOV. These negative findings contrasted with the above mentioned claimed results in the treatment of EBOV infection and highlighted the need for better comprehension not only of the characteristics and titre of antibodies able to affect the course of diseases but also of the role of the recipients' immune response. In 2012, Dye and colleagues reported that passively transferred species-matched polyclonal IgG were able to provide total protection in Filovirus-challenged non-human primates as well as the maintenance of sufficiently high levels of IgG after multiple administrations until the host's adaptive immune responses could be recruited to clear the viral infection. In the same year, Olinger et al. and Qiu et al. reported that neutralizing anti-EBOV glycoprotein monoclonal antibodies protected monkeys before and after lethal virus challenge.
Sources: ncbi.nih.gov; Wikipedia
September 9, 2020Quiz
An antibody (Ab), also known as an 1) _____ (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen, via the fragment antigen-binding (Fab) variable region. Each tip of the Y of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (for example, by inhibiting a part of a microbe that is essential for its invasion and survival). Depending on the antigen, the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region (located at the base of the Y), which contains a conserved glycosylation site involved in these interactions. The production of antibodies is the main function of the 2) _____humoral immune system.
Antibodies are secreted by B cells of the adaptive immune system, mostly by differentiated B cells called plasma cells. Antibodies can occur in two physical forms, a soluble form that is secreted from the cell to be free in the blood plasma, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B-cell receptor (BCR). The BCR is found only on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells that will survive in the body and remember that same antigen so the B cells can respond faster upon future exposure. In most cases, interaction of the B cell with a T 3) _____ cell is necessary to produce full activation of the B cell and, therefore, antibody generation following antigen binding. Soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms.
Convalescent Plasma the blood plasma of a person who has recovered from an infectious illness, which contains antibodies to an infectious disease factor (such as viruses). For convalescent plasma therapy, the plasma can be transfused into an ill victim of that disease as a treatment.
The US FDA has issued an 4) _____ use authorization for convalescent plasma to treat Covid-19. However, the published research studies have not been peer-reviewed and do not describe a randomized clinical trial that proves Covid-19 convalescent plasma, or CCP, is effective. One of them presents pooled data drawn from CCP studies in multiple countries including China, Iran, Iraq and Mexico. In short, we need much more information than we now have.
The scientific basis of CCP therapy is giving an outside boost to a patient battling the virus. The plasma contains virus-neutralizing 5) _____ -- proteins that recognize the invading virus, bind to it at specific locations and prevent it from infecting human cells. They neutralize the virus. CCP therapy is very soundly based on decades of experience with other infections. It's generally considered quite safe, but all blood products carry some risk, including rare but fatal transfusion reactions and transfusion-transmitted infections. But CCP therapy can only work well when the patient receives enough antibodies to make a difference. The amount of antibodies in the blood of Covid-19 patients depends on the severity of the infection and when the measurement is made. The sickest patients have the most antibodies, even those who go on to die. People with mild symptoms who recover at home usually have only very low levels of these antibodies. The best donors are seriously ill hospital patients who recover, are discharged and then give their plasma within the next month or two. Plasma donations from people who recover from mild infections are all too often not useful.
CCP therapy is not a simple procedure. Considerable efforts are being made to obtain suitable plasma units and then use them. There's enough knowledge already around, including preliminary information from randomized clinical trials, and the hints in the 6) ____ Clinic manuscripts, to know that it's best to hit early, hit hard. But to use CCP therapy effectively, only the most antibody-rich plasma should be used. And it should be given early, within the first week after the patient enters hospital, preferably the first three days..
Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from 7) ____ to people who need them is being investigated as a non-vaccine method of passive immunization. This strategy was tried for SARS with inconclusive results. Viral neutralization is the anticipated mechanism of action by which passive antibody therapy can mediate defense against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for 8) _____ antibodies. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may be possible. Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development. Antiserum is human or nonhuman blood serum containing monoclonal or polyclonal antibodies that is used to spread passive immunity to many diseases via blood donation 9) (_____). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for 10) _____ infection with a high success rate of 7 out of 8 patients surviving.
Antisera are widely used in diagnostic virology laboratories. The most common use of antiserum in humans is as antitoxin or antivenom to treat envenomation.
Sources: nih.gov; CNN.com (Sanjay Gupta); Wikipedia
ANSWERS: 1) immunoglobulin; 2) humoral; 3) helper; 4) emergency; 5) antibodies; 6) Mayo; 7) COVID-19; 8) neutralizing; 9) plasmaphoresis; 10) ebola
September 9, 2020What's New
DPHARM is the annual event sponsored by The Conference Forum, for clinical operation professionals to get the best access to innovative ideas, especially disruptive ones, to advance drug development with a view to reducing the burden to patients and investigators. Attendees leave DPHARM with a host of ideas to solve current challenges in clinical trials and better prepared for the expectations for 21st Century drug development with an extended network of strategic level thinkers.
At 11:30 on September 22, Dr. Jules Mitchel, CEO of Target Health LLC will present a talk entitled On Learnings From a COVID-19 Study that Used E-Informed Consent and Realtime Direct Data Capture. The following is a summary of what to expect.
Doing research in the time of COVID-19 is like doing a study in a war zone. Patient encounters are limited and the use of paper informed consent documents (eICD's) and paper source records for initial data capture in the ICU or COVID-19 unit are not allowed. Tablets secured in a sterile environment connected to the internet are acceptable which allows for electronic signatures and remote data capture. In this case example, while these paperless tools were not universally accepted in an ongoing COVID-19 study, there was clear adoption by some of the sites.
For more information about Target Health, contact Kathleen Kane Tremmel, Vice President, Business Development. For those who have been working with Warren Pearlson, Director, New Business Development, please continue to do so. For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Also visit the Target Health Eating Website to see all of the fantastic recipes since 2012.
Joyce Hays, Founder and Editor in Chief of On Target
Dr. Jules T. Mitchel, Editor
August 10, 2020Target Healthy Eating
1 carrot, boiled or roasted until soft, peeled, diced into small cubes
1 large parsnip, boiled or roasted until soft, peeled, diced into small cubes.
1 large stalk celery from hearts of celery, minced
1 ear of fresh corn, kernels scraped off
3 anchovy fillets ground in mortar & pestle with 3 fresh garlic cloves = paste
1 bunch fresh parsley, washed, drained, patted dry with paper towel, then well chopped
1 bunch fresh dill, washed, drained, patted dry with paper towel, then well chopped
2 large red potatoes, baked or boiled, skin peeled, cut into small cube shapes
1 apple, peeled, quartered, pitted, cored, then cut into small pieces
3 cloves of garlic, minced
1/2 onion, chopped well
5 pickled cucumbers, (Polish pickles preferred), well chopped
8oz of frozen green peas, thaw to room temperature
1 pinch black pepper
1/4 cup Kraft mayonnaise (more is optional)
3 large eggs (hard boiled) boiled in salted water 10 minutes, plunged into icy water. Peeled, then chopped
1. Do all your chopping, cutting, grinding, mincing first.
2. Roast or boil the carrot and the potatoes until they are soft (45 to 60 minutes)
3. Prepare the apple. When cut into small pieces, put all into the salad bowl
4. Mix the anchovy/garlic paste with the mayonnaise, as well as the black pepper, parsley and dill.
5. Boil, cool, peel the eggs; then chop them and put into the salad bowl.
6. Chop or dice all the veggies and put into the salad bowl you plan to serve from.
7. Add the mayonnaise mixture and stir it into the veggies, until all is well combined.
8. Add which ever garnish you've decided on using.
For garnish, consider red pomegranate ariles (seeds). Or dried cranberries, chopped very fine. Or fresh strawberries chopped very fine.
We recommend this lovely bright, tropical fruity chilled Sauvignon Blanc that we've been sipping for many summers. In addition, this is a reasonably priced wine.
Wine Critic Ratings
91 Points James Suckling
95 Points Bob Campbell (MW)
You can carry on, the torch of peace and brotherhood and simply live by the Golden Rule!
From Our Table to Yours
Have a Great Week Everyone!
August 10, 2020Regulatory
Spinal Muscular Atrophy refers to a group of hereditary diseases that damages and kills specialized nerve cells in the brain and spinal cord (called motor neurons). Motor neurons control movement in the arms, legs, face, chest, throat, and tongue, as well as skeletal muscle activity including speaking, walking, swallowing, and breathing. The most common form of SMA is caused by an abnormal or missing gene known as the survival motor neuron gene 1 (SMN1), which is responsible for the production of a protein essential to motor neurons. This form of SMA has four types:
1. Type l, also called Werdnig-Hoffman disease or infantile-onset SMA, is usually evident before 6 months of age. The most severely affected children will have reduced movement and chronic shortening of muscles or tendons (called contractures). Other children may have symptoms including reduced muscle tone, lack of tendon reflexes, twitching, skeletal abnormalities, and problems swallowing and feeding. Without treatment, many affected children die before age 2 years.
2. SMA Type ll is usually first noticed between the 6 and 18 months of age. Children can sit without support but are unable to stand or walk unaided. Children also may have respiratory difficulties. Life expectancy is reduced but most individuals live into adolescence or young adulthood.
3. SMA Type lll (Kugelberg-Welander disease) is seen after age 18 months. Children can walk independently but may have difficulty walking or running, rising from a chair, or climbing stairs. Other complications may include curvature of the spine, contractures, and respiratory infections. With treatment, most individuals can have a normal lifespan.
4. Individuals with SMA Type IV develop symptoms after age 21 years, with mild to moderate leg muscle weakness and other symptoms.
The FDA has approved Evrysdi (risdiplam) to treat patients two months of age and older with SMA. Evrysdi contains a survival of motor neuron 2-directed RNA splicing modifier. This is the second drug and the first oral drug approved to treat this disease.
The efficacy of Evrysdi for the treatment of patients with infantile-onset and later-onset SMA was evaluated in two clinical studies. The infantile-onset SMA study included 21 patients who had an average age of 6.7 months when the study began. In that open-label study, efficacy was established based on the ability to sit without support for at least five seconds and survival without permanent ventilation. After 12 months of treatment, 41% of patients were able to sit independently for more than five seconds, a meaningful difference from the natural progression of the disease because almost all untreated infants with infantile-onset SMA cannot sit independently. After 23 or more months of treatment, 81% of patients were alive without permanent ventilation, which is a noticeable improvement from typical disease progression without treatment.
Patients with later-onset SMA were evaluated in a second randomized, placebo-controlled study. The study included 180 patients with SMA aged two to 25 years. The primary endpoint was the change from baseline in MFM32 (a test of motor function) total score at the one-year mark. Results showed that patients on Evrysdi saw an average 1.36 increase in their score at the one-year mark, compared to a 0.19 decrease in patients on placebo (inactive treatment).
The most common side effects of Evrysdi include fever, diarrhea, rash, ulcers of the mouth area, joint pain (arthralgia) and urinary tract infections. Patients with infantile-onset SMA had similar side effects as individuals with later-onset SMA. Additional side effects for the infantile-onset population include upper respiratory tract infection, pneumonia, constipation and vomiting. Patients should avoid taking Evrysdi together with drugs that are multidrug and toxin extrusion substrates because Evrysdi may increase plasma concentrations of these drugs.
The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage drug development for rare diseases. The application was awarded a Rare Pediatric Disease Priority Review Voucher.
The FDA granted this approval of Evrysdi to Genentech, Inc.
August 10, 2020Tropical Medicine
In 2018, the World Health Organization reported that there were 228 million cases of malaria worldwide, leading to more than 400,000 deaths, 67% of which were among children under 5, According to a paper published in Nature Communications (30 July 2020), another set of pore-like holes, or channels, traversing the membrane-bound sac that encloses the deadliest malaria parasite as it infects red blood cells has been identified. The channels enable the transport of lipids - fat-like molecules - between the blood cell and parasite, Plasmodium falciparum. The parasite draws lipids from the cell to sustain its growth and may also secrete other types of lipids to hijack cell functions to meet its needs.
The finding follows an earlier discovery of another set of channels through the membrane enabling the two-way flow of proteins and non-fatty nutrients between the parasite and red blood cells. Together, the discoveries raise the possibility of treatments that block the flow of nutrients to starve the parasite.
In the current study, the authors determined that the channels through the sac, or vacuole, that encloses the parasite are made of Niemann-Pick C1-related protein (PfNCR1). The PfNCR1 channels are restricted to locations where the vacuole membrane touches the parasite's membrane. The channels the team discovered in the previous study are formed by exported protein 2 (EXP2). Areas of the vacuole membrane containing EXP2 are located far from the parasite's membrane, at an average distance of 20 to 40 nanometers. The authors believe that the parasite may use this variation in distance to separate the two transport systems.