Patient Empowerment Program: A Rare Disease Podcast

Advocating for Rare Patients

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.

Drug Discovery Platforms

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.

Clinical Trials for One Patient

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.

How Drugs are Used

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.

A Diagnostic Odyssey: The UDN and n-Lorem’s Roles

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.

Biological Systems & Chemical Networks

We are all chemical engines. So, what exactly is a chemical? Chemicals are anything that occupies space in the universe and exist in either a solid, liquid, or gas form – matter! Chemicals within living organisms are considered biochemicals and are organized into chemical networks (an integrated chemical process that establishes life and the maintenance of homeostasis). Homeostasis is simply a scientific term that means maintenance of the status quo. So, a healthy living organism must respond to its environment and manage different threats. The systems that are designed to ensure that the cell remains healthy are called homeostasis. Drugs are also chemicals. Drugs enter an organism and make their way through biological systems to interact with many chemicals. Sometimes those interactions lead to changes in the chemicals with which the drugs interact, altering one’s physiology or psychology. One must have a keen understanding of basic scientific terminology, these chemical networks, and biological systems to create drugs and use them to make a difference in all patient populations. Ready? Let’s get started.

What is n-Lorem?

n-Lorem provides an opportunity for a better life, renewed hope and brighter dreams, one patient, one family at a time. Our mission is to provide personalized experimental antisense oligonucleotide (ASO) medicines to treat nano-rare patients – for free, for life. Nano-rare patients describe a very small group of patients (1-30 worldwide) who, because of their small numbers, have few if any treatment options. We take advantage of the efficacy and versatility of ASO technology. ASO technology is the only technology with regulatory guidance to treat nano-rare patients. Rare diseases often cause people to do things that they’re completely untrained to do. With this series, we’re building a community for nano-rare and bringing the basic science behind drug discovery and development directly to patients and their families.

Susannah’s Story with Dr. Wendy Chung and Luke Rosen

Dr. Stan Crooke talks to Luke Rosen and Wendy Chung about Luke’s seven-year old daughter, Susannah. Susannah has a genetic mutation that is progressive and debilitating. Susannah is also an n-Lorem patient, which means that we are hard at work discovering and developing a personalized experimental ASO medicine just for her, for her specific mutation. Her doctor, Wendy Chung, and Luke discuss Susannah’s life, her diagnosis and disease progression and the hope that they both have that there will be something that will make life better for her.

Patient Empowerment Program

We are excited to announce n-Lorem’s brand new podcast, the "Patient Empowerment Program".There are podcasts about genetics and rare diseases, but we didn’t find one focused on nano-rare diseases, conditions that affect 30 or less people in the world. Listen to this trailer to hear a sneak peak at what’s coming up on the podcast.There are going to be two types of episodes on this podcast, interviews and lessons. All episodes are hosted by biotech titian, Dr. Stan Crooke. He is the Founder, Chairman and CEO of the n-Lorem Foundation. Here’s how you can support our podcast launch: Rate & Review the podcast on Apple, Spotify, or wherever you listen. This truly helps us climb the charts and allow others to find the show. After you do that send it to a friend who you think will enjoy our podcast. And good news, you don’t have to wait long for the podcast, we are launching next week on May 25th, 2022 with three new episodes! So hit that subscribe button. For more information about n-Lorem and our podcast visit nlorem.org. Any questions can be sent into podcast@nlorem.org. Stay updated with the show by following us on social media, search “n-Lorem” on all platforms. Our videographer is Jon Magnuson of Mightyone Productions. Our producers are Kim Butler, Amy Williford, Jon Magnuson, and myself, Kira Dineen of "DNA Today".