Archive for the ‘Medicine’ Category

Rare Diseases: a parent’s journey

Friday, February 2nd, 2018

Journey is really the best word.  Thirty years of researching, detoxifying the home environment, creating an organic, colorful and nutrient rich diet, increasing the oxygen infusion in the blood and to the brain, employing creative hands-on learning techniques, and working through day long sessions of physical therapy and yet there was always that feeling that we were riding a roller coaster. The neurologist had told us to expect that wild ride when they attached the diagnosis of Lennox-Gastaut Syndrome (LGS) to my daughter. “There will be bad periods of seizures and then things might get better, just for a while. Keep in mind, LGS is just a description of a group of signs and symptoms often found together in patients, it is not the organic cause for her symptoms,” he explained. For us as parents, it was a holding pattern or a waiting room, until someday we might know the real cause. That cause was to remain a mystery until just after her 30th birthday. The wait came with a good deal of wondering.  Could we have…What if… Should I be doing this or that…? Most of these questions had to do with whether we were doing our best for our precious daughter.  She was ten when a sense of peace came over me, not based on my understanding of the problem but based on faith.  This was not about whether I could solve the medical mystery; that was not going to be my discovery to claim.  Instead it was about being faithful to the care and love for my daughter.  And so we kept current on the science and dove even more deeply into the care and relied on physicians and therapists who stood beside us steadfastly. And the doctors were right about the roller coaster. There were real victories for her: she went from an ataxic awkward walk to a 12 minute mile run, single words changed to complete sentences, unable to get free from gravity to 500 jumps in a row, holding her breath in the pool to a water worm, and not recognizing letters and numbers to reading and understanding at the 5th grade level! But there were low points too, countless medication changes, daily shots for growth and allergies, loss of her front teeth as her cerebellar atrophy progressed, and most significantly, the ruptured appendix and unrelenting seizures that necessitated four successive hospitals over three months, and an induced coma resulting in paralysis. She is wheelchair bound now but still wakes every morning with joy on her face ready to take on her job, a full day of therapy, she is determined to  make more progress.  Her indomitable optimism, faith and humor have enriched all of our lives. There have been sacrifices.  Her dad has been her fearless hero with his tickles and his nicknames, her sisters have fed, slept with, and helped her with therapy when they could have been with their friends, family members have cared for those precious sisters in our absence when she was hospitalized, a law career was shelved, ball games were missed and vacations cancelled. But she has been as inspiration to all of us and has had an adhesive affect that has joined our extended family at the hip. She is our hero. We felt that someday we would know the cause of her problem and that day finally came on August 16, 2017 in the form of a genetic test and report showing a de novo mutation in the KCNA2 gene, a gain of function mutation that interferes with her brain. As far as I can tell there are seven other people in the world with the R297Q mutation.  Because of privacy rules, I have not found them, yet, but while I search, I am researching tirelessly. And when I find them (and will!) I will be armed with information to share as we march to finding a treatment together.  We are not going to ride the roller coaster anymore, we are going to put on our running shoes, find our team mates and jump the hurdles until we find hope help for my beloved daughter and for the young children whose full and happy lives will be ahead of them.

This Blog Post was written by a Mom and her journey with a daughter diagnosed with a rare genetic disorder. I will not disclose the name of both the mother and daughter for their privacy. If there are other parents, relatives and/or patients with this disease and this specific genetic mutation described here please “Contact Usat Genome For more information on rare disorders please check my last article entitled “Rare Genetic Diseases: Update on Diagnosis, Treatment and Online Resources”.

 Image Source: Global Genes – a Rare Disease Initiative

Diabetes, Obesity and Genetics

Friday, July 18th, 2014

Doctors and researchers have found that obesity and diabetes are connected. People who are obese are at high risk for developing Type 2 diabetes (also known as “insulin-resistant” or “adult-onset” diabetes), particularly if a close family member is affected with diabetes. Therefore, it becomes very important to maintain a healthy body weight throughout your life in order to protect yourself from developing a chronic disease like diabetes. Researchers have also determined that only a slight predisposition for obesity is inherited. For example, the best way for children to avoid being overweight is to eat a diet that is balanced and is low in fat. This diet should consist of lots of fresh fruits and vegetables. Snacks like chips, cookies, ice cream, and soft drinks should be limited or eliminated. This may require a lifestyle change in a person’s life. It is very important that all children become involved in physical activities on a daily basis. Too many children spend their free time in front of computers, television, and video games, and this results in a growing number of kids who are obese and who will likely suffer medical consequences of obesity as adults. In order to become a diabetic, two factors need to be present. First, you need to inherit a predisposition to the disease, and second, the environment must trigger a response in your body. Your genes alone are not enough. This has already been shown in studies of groups of identical twins: when one of a pair of twins develops diabetes, there is only a slightly increased chance that the other sibling will develop the disease. Because identical twins are genetically similar, the environment of the individual might play a role in the development of diabetes. However, because both genetics and the environment are shared by family members, we recognize that people with a family history for diabetes have a greater risk for developing the disease. Another factor are epigenetic marks that change with diet and the environment. Molecular biology has shown the genetic and epigenetic basis for the development of both diseases. In recent years, expanded knowledge of the human genome has led to the development of new tools that facilitate the simultaneous analysis of thousands of genes for complex diseases. Researchers now rely on such tools in their search to uncover the gene networks associated to conditions such as diabetes and obesity. Today, geneticists use a number of forward approaches (for example, approaches that seek to find the genetic basis of a phenotype) in their efforts to understand how gene networks may contribute to these diseases. One such method is the genome-wide association study or GWAS; this high-throughput approach allows geneticists to scan the entire human genome in an unbiased manner, using statistical methods to determine associations between chromosomal loci and a given phenotype. For example, a recent genome-wide association study has reproducibly associated variants within introns of the gene FTO with increased risk for obesity and type 2 diabetes (for more information see “Obesity-associated variants within FTO form long-range functional connections with IRX3” by Smemo et al). Mutations in introns (noncoding regions) of the gene FTO have been widely investigated after genome-wide association studies revealed a strong link between FTO and diabetes. Yet, overexpressing or deleting FTO in animal models affects whole body mass and composition, not just fat, and experiments have failed to show that these obesity-linked introns affect the function of the FTO gene itself. Diabetes and obesity are directly involved since body fat and metabolism are strongly connected. This study showed that not just proteins are associated to obesity, but also non-coding regions such as enhancers and introns. Conformational changes in the DNA and epigenetics (mostly linked to diet and environmental exposure) might be the answer to better understand both diseases. However, until we completely uncover the mysteries of the genetics of metabolism, the best choice is to eat healthy and live well, independent on genetic predisposition and background. Like they say; you are what you eat. So, eat well and exercise.




Human Evolution and the Birth of Medicine

Thursday, May 29th, 2014

There is no discussion: human and apes are close relatives with a common ancestor. Evolution studies confirm this hypothesis with different fossils differing in age with traces of genomic DNA and molecular features between these two species. Social science in apes also tells us that they are always in groups, have a structure of hierarchy and respect such as human societies. However, some questions remain, such as how primates deal with diseases and pain. In many traditional societies around the world people are very dependent in plants for both food and medicine. Close to a century ago, for example, a Tanzanian medicine man, Babu Kalunde, discovered an important treatment that saved the lives of many people in his village, who were suffering an epidemic of a dysentery-like illness. He learned about the potential medicinal value of a plant known as mulengelele by observing a sick animal eat the roots of the plant. This is a fact: animals in the jungle have to learn about medical plants and how to self-medicate. And this feature passes from generation to generation with parents teaching youngsters what to eat when they feel specific types of pain. Most of the details about two types of self-medicative behaviorin the great apes – namely, bitter-pith chewing and leaf swallowing – come from three study sites, Mahale and Gombe inTanzania and Kibale in Uganda, although these behaviors have been documented from 10 additional sites across Africa. The geographical, ecological, and climatic variation of these sites is great, ranging from low-elevation, moist tropical forest and woodland to forest. Such wide variation in geography, ecology, and climate where leaf swallowing and bitter-pith chewing are known to occur suggests that great ape populations elsewhere on the continent might also engage in these behaviors (for more information see “Self-Medicative Behavior in the African Great Apes: An Evolutionary Perspective into the Origins of Human Traditional Medicine” by Michael A. Huffman). Primates generally self-medicate with plants in the jungle and teach others what to eat depending on the pain. Specific plants for stomach pain are always shown to members of the community and offspring. The strong similarities in plant selection criteria among the African great apes in response to parasite infection and gastrointestinal upset, and the common use of some plants by chimpanzees and humans to treat such illnesses, are tantalizing evidence for the birth and evolution of medicine. Our earliest hominid ancestors may have exhibited some similarities in plant selection criteria with both extant apes and modern humans. Although the fossil record provides no direct evidence concerning specific feeding behavior and diet, it seems reasonable to hypothesize that early hominids would have displayed at least the range of extant ape self-medicative behavior. It appears that the fundamentals of perceiving the medicinal properties of a plant by its taste, smell, and texture have their roots deep in our primate history. A major turning point in the evolution of medicine is likely to have been the advent of language in early humans, which enabled people to share and pass on detailed experiences about plant properties and their effects against disease. That probably was the birth of medicine on earth. Since then, medicine continues to evolve, but if we go back to the jungle, primates use the same medical plants for generations to treat different types of pain. I believe we can learn a lot from them, especially to accelerate the development of new drugs for specific diseases. The bottom line is that primates are smarter than we think…



“Dallas Buyers Club” and HIV testing

Monday, February 3rd, 2014

What would you do if you were tested positive for HIV in a routine blood exam? Well, this question came up after I saw the movie Dallas Buyers Club. The movie portrays the life of Ron Woodroof, who was a Texas cowboy and drug user and was diagnosed with AIDS in the 1980s. He was initially given 30 days to live, but Woodroof (portrayed by actor Matthew McConaughey) begins taking azidothymidine (AZT), the only HIV drug legally available in America at that time. Woodroof goes on to travel the world, searching for medications that will keep him alive, and as a result, the Dallas Buyers Club is formed.  With the help of a doctor and another patient played by Jared Leto as a transsexual, Woodroof begins selling smuggled drugs out of a motel in Dallas, providing HIV-positive patients with alternative forms of treatment for their disease, since the FDA was still testing the drugs that are currently used. Interestingly, the storyline closely reflects the real life events of Ron Woodroof and provides a great example of how patient advocacy hastened the development of effective HIV medications during the 80s. I watched the movie and it was clear how the process of drug approval and lab testing is still rudimentary. Coming back to my question in the beginning of this blog post, what if your HIV test comes back positive? Well, what if I say that the standard tests done for HIV have problems with numerous false-positives? The main and most widely test used is an immunoassay called ELISA that measures antibodies against the virus. However, viruses are very similar and have building blocks or proteins that look alike. So, when you measure antibodies against a response of the human body for a viral infection, false-positives can occur. Indeed, I am writing this post to give people awareness that, for example, flu vaccination could cause a false positive for HIV. Like I said, the viruses are very similar. The HIV GP160 protein exists in several viruses and has a lot of similar regions (see more at this report on the New England Journal of Medicine “Influenza Vaccination and False Positive HIV Results”). This protein is present in other virions too, especially a variety of flu related viruses. Thus, vaccination against any type of flu could generate a cross-reaction in the aforementioned immunoassay. In fact, there are several reports and groups of discussion online in which the most discussed subject is a false positive test result for HIV. Yes, that is scary and weird, but it is more common that we imagine. Given the escalating international awareness of various influenza strains and flu vaccination, it is very important for clinicians and patients to keep in mind that influenza vaccination may cause cross-reactivity with HIV antibody assays. The time course for such cross-reactivity remains mostly uncertain, but could be for months. If your HIV test was positive, take into account this possibility and ask for the use of a nucleic acid amplification test instead of the “Western blot” assay to confirm the enzyme immunoassay. People should and need to be aware of that. The movie Dallas Buyers Club just reminded me how science and research can be misleading within its own “rules”. Ron Woodroof tried to overcome these rules to save lives and himself. We all need to take care of ourselves, of course, using the law to do it. The take home message is that we still do not understand enough about the biology of viruses and confusions such as the one I discuss here could happen. So be aware!




Cancer Genomes and Personalized Medicine – are we there yet?

Monday, April 29th, 2013

Bioinformatics WideShot(Cropped)

Cancer is and was always a disease that frightened humankind. The diagnosis of the disease meant a death sentence some decades ago. However, things are changing for the better. Armed with the initial human genome sequence available in 2001 and hundreds of cancer genomes, we can now use targeted drugs for specific defects in cancer cells. Treatment for the disease will not be based in the tissue the cancer came from (examples include prostate, colon, breast, brain and others) like years ago, but in the genomic features of the cancer. A tumor from brain can have similar genetic defects and resemble more a tumor from prostate or even breast compared to other brain tumors. Most of these genetic flaws that have been identified with human cancer genome projects are relative newcomers to medical terminology, as are most of the anticancer drugs, still in early testing, that are aimed at them. Development of the new drugs has been affected by the falling cost and increased speed of decoding the DNA from cancer cells and the prospects of premium prices for drugs that specifically attack the molecular drivers of cancer (for more information see the article by Anne Eisenberg in the NY Times “Variations on a Gene, and Tools to Find Them”). The web is also helping in the fight against cancer. Data repositories have been created to guide doctors and patients that suffer from cancer helping them find the right drug for their disease type. One of such tools is the portal “My Cancer Genome” created by researchers at the Vanderbilt University in Tennessee, United States. The website started two years ago and now has more than fifty contributors from twenty institutions all over the world. The website lists mutations in different cancer types, as well as drug therapies that may or may not be of benefit for patients. Most of the drugs described in the website are in clinical trials and only a few have been approved by the Food and Drug Administration (FDA). However, the portal is free and doctors, researchers, patients, relatives and institutions can access, easing the translation of the findings in research laboratories to the bedside of patients. The users can also select a type of cancer, such as “melanoma” and add a gene or gene defect, let’s say “BRAF,” for instance, or “lung cancer” and “BRAF,” and see all types of mutations in the BRAF gene that occur in those cancer types. The users can then check for national and international drug trials aimed at these alterations. Another internet tool that is focused in cancer patients is the website “CancerDriver”. This solution is a Search Engine connected to a database that facilitates the identification of the right biomarker for different disease outcomes. These solutions can use data crowdsourcing to identify specific disease types, leveraging information to the final consumer – the cancer patient. The sequencing of cancer genomes with accumulating information in databases and the use of internet solutions by health care professionals and patients will definitely facilitate cancer treatment. Personalized Medicine for cancer is already here. Now we have to make good use of it to help treating this deadly disease in the years to come.

Genetic Diseases: new horizons, new hopes

Tuesday, October 23rd, 2012

Monogenic genetic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undiagnosed. Scientists have already identified genetic problems for more than 7,000 genetic diseases and around 500 of these already have applicable treatments. Thousands of disorders caused by a single gene defect have been characterized at molecular levels, but clinical testing is available for only some of them and many have clinical and genetic heterogeneity. Hence, unmet need exists for improved care and molecular diagnosis in infants. Because for some of these disorders the progression of the disease is extremely rapid, albeit heterogeneous, molecular diagnoses must occur quickly to be relevant for clinical decision-making. Fortunately, in the last three years, faster DNA sequencing machines or the so-called Next Generation Sequencing (NGS) together with improved data analysis tools have been able to facilitate the diagnosis of genetic disorders in days rather than weeks, and we can expect to do it in hours since technologies in this field are evolving fast. Whole genome sequencing, for example, can already identify new genetic defects, never seen or described before. Health care professionals can group children that have the same symptoms and genetic mutations, providing new clues on how to proceed to treat these patients. Armed with computer program searches for genes based on the baby’s symptoms, they can diagnose genetic diseases with more certainty (for more information see “Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units” by Saunders et al.). This way, new genetic disorders can be identified combining DNA sequencing with bioinformatics and the symptoms or morphological defects of the children. Diagnosing unidentified diseases will add more information to the biomedical field and help pharmaceutical companies identify and test new drugs (see also “Rapid test pinpoints newborns’ genetic diseases in days” by Monya Baker). These tests could represent one of the first practical fruits of the revolution in sequencing an individual’s entire DNA (see the article “Infant DNA Tests Speed Diagnosis of Rare Diseases” by Gina Kolata in the NYTimes). This brings new market opportunities for genetic testing, biotechnology and pharmaceutical companies. Tests such as whole genome sequencing that reveals fatal genetic diseases could also improve genetic counseling by informing parents on their probabilities of having new children with the same defects. Most genetic diseases have no treatments yet; however, for the ones that are identified and there are treatments, this type of test will increase the chances for the babies to survive and avoid the problems caused by an undiagnosed condition. Whole genome sequencing still cannot diagnose all genetic diseases; however these new breakthroughs in medical genetics will enable a better diagnosis for many cases that would otherwise have remained harrowing mysteries. More research needs to be done before these tests make it to market and are covered by the healthcare system (it is still expensive, costing between 8,000-15,000 dollars), but these studies bring new hope for families of kids with genetic disorders. (Image Source: GEN News)

P4 Medicine – a new revolutionary approach to treat diseases?

Wednesday, February 29th, 2012

The term “P4 Medicine” was first introduced more than 5 years ago by the researcher Leroy Hood in an attempt to change medicine from a reactive to a proactive perspective. The ultimate goal of this “futuristic medicine” is to maximize wellness for each individual rather than just treat the disease. P4 stands for the letter “P” in four words: Predictive, Preventive, Personalized and Participatory (for more information see “Predictive, personalized, preventive, participatory (P4) cancer medicine” by Hood and Friend). Emerging from debates related to health care system reform and translational research, this new way of thinking about medicine has put the focus on the patients, other than the physicians. P4 medicine utilizes four interconnected aspects to improve both the effectiveness and efficiency of health management at the individual level. The first “P” that stands for Predictive medicine studies the risk factors, predispositions, and genetic susceptibilities that exist before issues arise by the use of genetic testing and genome sequencing, technologies that have evolved in the last decade. This gives the patient and their health care team warning signs long before a disease is diagnosed. It also gives information that can influence changes in the diet and lifestyle of individuals. The second “P” for Preventive medicine uses the knowledge of the risk factors learned from predictive medicine to change a person’s behavior. It also helps in pre-disease treatments and early screening helping cut off the development of more serious conditions. The third “P” is for Personalized medicine in which each individual will respond differently to treatments. This helps the physician understand what works and what does not work. Personalized or individualized medicine studies and treats each individual as a unity and the current system of health care attempts to treat patients in a universal fashion, which is wrong. The knowledge and access to multiple treatment options as well as better predictions on what works more effectively will help patients and their health care team in selecting the treatment to best meet the patient needs, thus personalizing the medical experience. The fourth and last “P” is for Participatory medicine in which the patient and doctor relationship will become more interactive, helping in better diagnosis and effective treatments. Participation in health care decisions empowers the patient and can encourage innovation among the health care team. Importantly, the emergence of the Web 2.0 and social media websites is facilitating these interactions. Social Media is also empowering individuals to share their data with others that may have the same conditions. This new era in medicine has been shaped by technology breakthroughs such as increasing computer storage capacities and speed, the emergence of the cloud and systems biology generating tons of patient data points. This concept of enabling data and models to be shared by communities as maps of disease built in an open-source manner that includes researchers and physicians around the world will change the style and speed of discovery and development of new therapies. This revolution in medicine will also facilitate clinical trials that need to recruit a very large number of patients. It will be possible by the use of crowd-sourced recruitment bringing several centers and groups together with the use of next generation Electronic Medical Records (Next-Gen EMRs) empowered by social media tools. I truly believe that “P4 medicine”, with patients being more in charge of their own health data, will change the way we approach and treat diseases. That is indeed a medical revolution!

Translational research and applied medicine – are we all lost in translation?

Saturday, March 5th, 2011

In this blog post today, I will share some experiences in my day-to-day life doing (or trying hard to do…) translational research. Just to be clear there are two main types of research: 1) basic, which tries to understand the fundamental principles and phenomena that drive cells, organisms, systems and the world we live in; and 2) translational, which is the application of the basic research to solve specific problems, aid in diseases and help the society at different levels. In health sciences, translational research has its focus on removing barriers to multidisciplinary collaboration between scientists and physicians helping to “translate” basic discoveries in new drugs to treat diseases and/or the identification of better ways to manage chronic diseases such as cancer, diabetes, etc. Importantly, translational research has the potential to drive the advancement of applied science. It is also an attempt to bridge the medical and scientific domains to move discoveries “from bench to bedside” or from laboratory experiments through clinical trials to actual point-of-care patient applications. Well, it is pretty and fancy to say that you are doing translational research, since the chances that your research will help improve patient care are always higher. I can tell using my personal experience that this is a very complicated and entropic process. As in any field, communication is key to success. For example, in project management, business, finance, and etc, communication has to be the most important feature in the path to success. The same applies to multidisciplinary projects involving scientists, project managers and physicians. The problem is that it is not like this. Physicians have different expectations compared to scientists and I have a feeling that I am always “lost in translation” and vice-versa. The success of any project depends not just in commitment from the personal involved but also good communication skills between the people that are involved. It is like in the cartoon above, there is a “valley of death” between both parts mainly because the exchange of information is faulty. Well, we are in need for better ways to facilitate the communication between professionals with different backgrounds, especially when doing translational research. The physician needs to understand and be interested in the scientific side of the project (read more, study more, be curious about science which sometimes is not the case…) and the scientist has to understand the physician’s needs and the problems he or she wants to find answers in order to increase the rates of success. My feeling is that none of this happens and the environment between both sides is indeed entropic with constant miscommunication. Improvements in both sides for a better information exchange are crucial to develop multidisciplinary projects with impacts for patients suffering from diseases. New discoveries doesn’t depend just on working hard towards a goal, there might be a synchrony between researchers and doctors so the rate of success will increase extraordinarily. Finally, I believe that both parts need to learn more about Project and Finance Management, especially in though times with shortage of money for research. I think this is not an isolated case and this may happen in a lot of institutions around the world. So, let’s step back for a while and think on how to maximize our chances of better communication and, consequently, of success in translational research.