Manish Raisinghani joins the Patient Empowerment Program to discuss how Target ALS fosters collaboration between academia and industry to research and accelerate the fight against ALS. Target ALS has funded over 50 collaborative projects. Greater than 50% of which have had an industry partner and over 60% have resulted in an ongoing drug discovery program. From their Innovative Ecosystem, 6 clinical trials have emerged. Target ALS’ commitment to fight all forms of ALS, no matter how rare, is evident in their founding support of Silence ALS, an initiative that aligns Columbia University and n-Lorem to offer an integrated solution to identify, support and potentially treat nano-rare ALS patients. Target ALS hopes that one day, no patient, no matter how rare their form of ALS, is left behind. On This Episode We Discuss: Target ALS’ innovative model Accelerating ALS research through collaboration  How a single nano-rare study can inform the ALS research landscapeThe importance of understanding the fundamental biology behind ALS Committing to fight all forms of ALSTarget AlS’ support for n-Lorem and Columbia University’s Silence ALS Initiative

Regardless of the circumstances, life finds a way! Jurassic Park got that one right. Cells need to live and depending on the conditions they will use one of two systems that take nutrients, break them down and use that process to generate energy. That energy is needed to sustain life – hence why it is called The Energy of Life. All the order that you see in the night sky, like planets, star clusters and galaxies, are due to an incredible amount of energy in the universe, creating order out of chaos. The amount of chaos and disorder is measured in entropy. In this episode, the energy of life, entropy and how we convert, store and use energy is explored.Visit www.nlorem.org

Dan Doctoroff joins the Patient Empowerment Program to talk about his mission to support a world where everyone with ALS lives. Dan is the former NYC deputy mayor for economics and former CEO of both Bloomberg L.P. and Sidewalk Labs. In this episode, Dan discusses his family’s battle with amyotrophic lateral sclerosis (ALS), his own inspiring story of how his diagnosis completely changed his outlook on life and his work with the foundation he started, Target ALS. On This Episode We Discuss: Dan’s inspiration to bring the Olympic Games to NYC 3 things he learned as a CEO Dealing with the reality of being diagnosed with ALS Shifting his perception of life How ALS has impacted his bloodline Scaling up Target ALS and fighting for the lives of every ALS patient

If your car’s oil filter is clogged, it’ll lead to severe issues within your engine. The same goes for the blood filters of your body... but worse. The kidneys filter water-salable waste from the blood. As kidneys fail, waste builds up. A blockage in your kidneys may cause a heart attack, stroke, or kidney failure. Detecting kidney disease early on can save lives! While kidney disease isn't reversible, it can be treated to slow or stop the progression of the disease.n-Lorem is accepting nano-rare kidney patients for treatment. Information about the application process and can be found at www.nlorem.org/access

There is so much filtration around you, you may not even notice. Your water, coffee, air, gasoline, and social media feeds... all filtered. So is your blood! It's just a part of everyday life at this point. This episode of the Patient Empowerment Program focuses on the functions of the spigot of the cardiovascular system – the Kidneys. Their main job? To remove water salable waste from the body along with other functions that are necessary for life. Did we mention that n-Lorem is accepting nano-rare kidney patients for treatment? Information about the application process and can be found at www.nlorem.org/access

Drip... Drip. When your pipes are leaking, it's never a good thing. Who you gon’ call, YOUR DOCTOR! The next lesson in our ‘pipe’-line focuses on the pipes of the cardiovascular system - the Arteries and Veins. Learn about the arterial and venous systems that manage blood flows with differing pressures, high and low. However, both systems have mechanisms that control blood flow under unique conditions to supply our tissues with nutrients, remove waste, and keep us alive. In the event of a busted pipe, know that a plumber can’t help you. Call a doctor, because the pipes in your body are much more complex and interactive with the materials inside than the ones in your home.

This episode is sponsored by our partner, Parexel, one of the world’s largest clinical research organizations (CROs) providing the full range of Phase I to IV clinical development services. Parexel provides clinical operations, real-world data solutions, medical and regulatory expertise and innovative clinical research tools that significantly enhance and streamline n-Lorem’s therapeutic development efforts. Their depth of industry knowledge and strong track record gained over the past 40 years is moving the industry forward and advancing clinical research in healthcare’s most complex areas, like rare disease. Jamie Macdonald, CEO of Parexel, joins Stan to discuss the moment he realized his desire to make a difference, Parexel’s role in clinical trials and their partnership with n-Lorem aimed to serve patients.

In this episode, Stan continues his lecture series on organs, concluding his lesson on the pump of the cardiovascular system, the Heart. Organs are individual tissue components that help meet the needs of an entire organism (that's you). The heart is one of the most important, complex, and fascinating organs in your body - and we couldn't squeeze it into just one episode! Learn all about heart diseases in the final installment of this two-part series.

In this episode, Stan continues his lecture series on organs, focusing on the pump of the cardiovascular system – the Heart. Organs are individual tissue components that help meet the needs of an entire organism (that’s you). The heart is one of the most important, complex, and fascinating organs in your body. Learn all about the heart that’s working so hard for you in the first of a two-part series on this amazing organ.

This episode is sponsored by our partner, Ultragenyx, a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases! Ultragenyx has been a loyal and proud supporter of n-Lorem and our patients.  Stan talks with a rare disease treatment advocate and the CEO, President and Founder of Ultragenyx, Emil Kakkis, MD, PhD, about why he has dedicated his career to supporting the rare disease community, what led him to establish the EveryLife Foundation, and the origins of Ultragenyx. Because of the debilitating and often quick progression of rare disease patients, Emil believes that regulatory agencies should modify the way they approach clinical trials for these individuals. Far too often, policies leave patients stuck waiting and hoping for treatment while their symptoms worsen, causing permanent damage. Do you have a question that you’d like to ask Stan Crooke? Stan will be taking questions directly from you and other podcast listeners and dedicating an entire episode towards answering your questions! To submit a question for the upcoming Q&A episode, email podcast@nlorem.org with the subject line labeled “podcast question”. If you wish to be identified, mention your name in the email. If not, we will keep your submission anonymous. We can't wait to hear from you!

Focusing on the cardiovascular system, Stan starts a new lecture series on organs. No, not the state in the Pacific Northwest and definitely not the large piped musical keyboard you’d find in a church or a ballpark. We’re talking about the collection of tissues within the body that perform vital functions for life. Organs! Part 1 focuses on that warm red liquid inside of you, blood! Now blood is not technically an organ. But, according to Stan, it should be. Dr. Crooke covers how the blood cycle delivers nutrients and oxygen to other organs through the hemoglobin protein, the factors and checklist of blood clotting, and discusses a few of the countless mutations within blood cells that cause both common and rare diseases.

When Stan Crooke, M.D., Ph.D., ran Ionis and John Maraganore, Ph.D., ran Alnylam, they were partners that turned into rivals — and not always friendly ones — as they persevered to pursue an entirely new therapeutic space; RNA-targeted drug discovery and development. Now, the pair of drug discovery titans have united once again in support of Dr. Crooke’s n-Lorem Foundation—working to provide experimental personalized medicines to the rarest of rare disease patients (nano-rare) using the antisense oligonucleotide (ASO) technology he developed at Ionis. In this episode, Stan speaks with Dr. John Maraganore about John’s past, their former rivalry, and the optimism shared between the two with respect to the future of n-Lorem.Do you have a question that you’d like to ask Stan Crooke? Stan will be taking questions directly from you and other podcast listeners and dedicating an entire episode towards answering your questions! To submit a question for the upcoming Q&A episode, email podcast@nlorem.org with the subject line labeled “podcast question”. If you wish to be identified, mention your name in the email. If not, we will keep your submission anonymous. We cannot wait to hear from you!

We’d like to thank our sponsor, Argonaut Manufacturing Services. Argonaut provides contract manufacturing and sterile fill-finish services for biopharmaceutical, diagnostics, and life science organizations. Argonaut’s expertise in sterile fill-finish is the last step in the complex process of providing personalized antisense oligonucleotide (ASO) medicines to nano-rare patients.When considering if the technology he led the creation of could be a viable way to develop a drug for a single patient, addressing their specific mutation, Dr. Crooke felt that he had to try, patients were dying without access to any treatment because they were just too rare. So began n-Lorem. As expected, developing an optimal ASO for a single patient is not an easy or simple process. Quality must lead every step and only optimal ASOs can reach patients.Learn our science and processes behind the discovery and development of personalized ASO medicines for each of our nano-rare patients. n-Lorem’s mission is to provide hope and potential help to nano-rare patients – for free, for life; a mission that was impossible just a few years ago. This enables the non-profit approach that we believe is the only way to address the needs of nano-rare patients. Thanks to our partners like Argonaut, we are able to provide hope and potential help to patients today and tomorrow.

In this episode, Stan talks with Sonja and Dr. Neil Shneider, associate professor of motor neuron disorders at Columbia Medical School, about Sonja’s daughter, Anna. She is 17 years old and suffers an aggressive, fatal form of ALS. ALS is rare in teenagers, and this form of ALS is the worst of the worst. Sonja tells Anna’s story initial symptom onset, to diagnosis, and to Anna's response to ASO treatment. As a parent, Sonja reveals her full range of emotions during the duration of her daughter’s disease: puzzlement, pain, humility, and now optimism.

What makes antisense oligonucleotides (ASOs) so special? Let’s first understand what an oligonucleotide is. An oligonucleotide is a short strand of synthetic DNA, or a nucleic-acid chain, usually consisting of up to approximately 20 nucleotides read from left to right. n-Lorem’s ASO technology is based on thirty years of innovation and investment to make ASOs drugs with optimal qualities. This technology is also uniquely beneficial for nano-rare patients due to its specificity and broad utility to address the myriad of mutations that nano-rare patients present. Each a unique program with a unique challenge.Compared to other drug discovery platforms, discovering and developing an optimal ASO is inexpensive, quick and can be used to treat diseases that are caused by many different types of gene mutations. ASOs are designed to bind precisely with RNA, modifying the process of creating a disease-causing protein. Thereby making ASOs highly specific and a powerful drug discovery technology for nano-rare patients, who need a therapeutic approach that targets their specific gene mutation.

In this episode, Stan speaks with Wendy Erler about her involvement in the treatment of patients with rare genetic disorders. From her start in the pharmaceutical industry, to her involvement with every major platform of drug development, to her position as vice president and head of patient advocacy at Alexion; Ms. Erler has always ensured that a patient's voice is heard.Learn more about Wendy Erler on twitter @wendy_erlerPlease like and subscribe so that we can reach more potential patients and their family.

There are three validated methods of discovering drugs – called platforms. Small molecule drugs (SMD), monoclonal antibodies (mAbs), and RNA-targeted drugs. SMDs are, you guessed it, very small! Remember that the size of chemicals is measured in units called Daltons, which is capitalized because it is named after the scientist who invented the term. The smallest chemical is a hydrogen ion, and it is 1 Dalton. Small molecule drugs are generally less than 500 Daltons. Because of this, they don’t carry much information and are not very specific in their ability to bind to proteins. A small change can alter the behavior of the drug almost entirely.mAbs are man-designed, biologically made proteins and typically, are 60-70 thousand Daltons. Clearly, they are in orders of magnitude larger than SMDs and, as you’d expect, they behave very differently from SMDs. Because mAbs contain more information than SMDs, they are generally more specific. Though mAbs are much larger than SMDs, only a little bit of information in the mAbs is used to specifically interact with their target and yet, all that chemical information in the protein can interact with many other things and thus cause problems.These are more specific than SMDs and can target a single site on a protein or chemical. RNA-targeted drugs, like antisense oligonucleotides (ASOs) and SiRNAs, use genetic information to target a specific site on an RNA. n-Lorem takes advantage of the specificity and versatility of ASO technology. ASOs are highly specific, and we can continuously learn from successes and failures of the technology to predict how the next one will behave. Discover the in-depth differences between the three platforms, their triumphs and failures in modern drug discovery, their benefits and limitations, and why gene therapy is not on the list of drug discovery platforms… yet.

In this episode, Stan talks to Dr. Joe Gleeson about the role of genetics in neurology and pediatric patients with neurological conditions.  Early in his training, Dr. Gleeson realized how prevalent it was that pediatric patients, especially those with neurological disorders, never received a diagnosis.  Furthermore, in over half of these patients he felt that there were underlying genetic mutations causing these disorders.  With the advent of genomic sequencing, now many of these mutations are identified, however few have any therapeutic options available.  In this episode, the role of a genotype to define a phenotype is outlined and the need to shift our therapeutic approaches to be more action-orientated and addressing the underlying genetic cause not the symptoms. This requires a technology, like antisense, that is able to target a specific gene mutation.  When asked why n-Lorem, Dr. Gleeson expresses significant optimism that n-Lorem will be able to address a number of these previously untreatable patients.  Just diagnosing patients and treating symptoms is not enough, to make a meaningful impact on these patients, more needs to be done.  Through n-Lorem many patients will now have the chance.

Drugs are chemicals. They are like all other chemicals except that humans make a value judgement that a particular chemical (drug) will effect a desired change in a living organism. However, it’s important to note that a drug does what it does and there is no perfectly specific drug. So, drug effects always represent a mosaic of chemical interaction and effects. Each drug has properties that we humans hope will bring benefit to other humans. Those are the desired effects, but every drug produces effects other than the desired effect. Those are called side effects. But the drug doesn’t care – it just does what it does. In fact, often, what is a desired effect in one therapeutic setting, may be a side effect in another.As pharmacologists and physicians interested in treating patients with drugs, we are interested in several properties that all drugs have. These include the mechanisms by which the desired objective is induced, pharmacodynamics, the mechanisms by which the drugs may induce side effects, toxicology, and the mechanisms by which the body distributes and clears a drug from the body, pharmacokinetics. Put simply, we are interested both in what the drug does to the body and what the body does to the drug.Because drugs are chemicals and chemical reactions depend on collisions between two or more chemicals, drug effects are concentration dependent. We adjust the concentration of a drug in the body by adjusting the dose. All effects of drugs, with the possible exception of allergic reactions, are dose dependent. Therefore, we are interested in the doses that produce a desired effect and the doses that may produce undesired effects, or adverse events (side effects). A drug that produces a desired effect at a much lower dose than the dose required to produce an adverse event is usually considered a better drug. When we assess the difference between the dose that produces a desired effect and a dose that produces an adverse event, we are now analyzing a drug performance in a sophisticated way, and we are thinking about the term therapeutic index. This is the key parameter that you should always be thinking about when you use a drug.

Dr. Sessions Cole shares his career being a neonatal pulmonologist and his involvement in the undiagnosed diseases network, the UDN. Dr. Cole estimates that it can take up to 12 years to get a diagnosis for a patient with a rare genetic condition and that there could be as many as 30 million of these patients in the U.S. who are undiagnosed. The UDN is working to elevate the awareness of the diagnostic odyssey these patients undertake and diagnose up to one third of patients who are referred to the UDN.  Dr. Sesh is part of n-Lorem’s access to treat committee (ATTC), the committee that evaluates and recommends patients to n-Lorem.  Dr. Cole discusses the robust processes involved in the evaluation of each application to n-Lorem and the hope and value that n-Lorem is providing to nano-rare patients today.