Major advances over the past decades have transformed the management landscape of neuromuscular disorders. Increased availability of genetic testing, innovative therapies that target specific disease pathways and mechanisms, and a multidisciplinary approach to care including both transitional and palliative care contribute to timely and more appropriate management of conditions that are associated with a severe disease burden and often also a reduction of life expectancy.

There is an increasing number of consensus recommendations/guidelines that are a useful adjunct for establishing a timely and accurate diagnosis, and enable prognostication of disease-related complications, are a guide for multidisciplinary care and treatment, and expedite initiation of disease-modifying interventions. A number of these guidelines have been referred to in various cases, such as myasthenia gravis (MG), myotonic dystrophy type 1 and 2, chronic inflammatory demyelinating neuropathies (CIDP), and Duchenne muscular dystrophy (DMD), to name a few.

A three-month-old boy was seen at the outpatient clinic because of reduced spontaneous movements, which his parents had noticed for a few weeks. His legs lay to the side, he barely moved his hands, and his parents had to increasingly support his head when feeding him. For the past two weeks. drinking became slower. He also drank less and he choked daily. Coughing and crying had become weak compared with the first two months of life. Pregnancy, birth, and family history were unremarkable. He was the second child of unrelated parents and had one healthy sister who was three years old.

A 27-year-old woman consulted the neurology clinic because of progressive muscle weakness in legs and arms. She noticed increasing difficulty in walking, with a maximum walking time of 15 minutes when there was a slight upwards slope, climbing stairs, and lifting heavy things. She had more and more frequent falls in which it felt like her legs suddenly could not bear her weight anymore. Once she fell, she wasn’t able to get up from the floor without help. At the time of referral, she also experienced problems rising from a sitting position. She also mentioned problems with repeated movements due to fatigability, for example, when she walked or was cleaning out the dishwasher.

In retrospect, she remembered that she had had a ‘typical’ walk from the age of five and had never been able to run. A subtle tremor of her fingers was already present in kindergarten. Her medical history was otherwise unremarkable. She had two healthy siblings.

A 49-year-old man, who had always been very active, noted backache and pain in his neck starting four years ago. During this period, it became more difficult to rise from a chair and from his bed, to climb the stairs, or to carry heavy objects. Walking became a bit more difficult over time. He still went to the gym, but noticed that flexing his knees against resistance became more difficult. He slept well, could easily lie flat during the night, and did not experience myalgia, and there were no sensory disturbances. There were no symptoms of respiratory insufficiency. Family history was unremarkable.

Having covered the discovery of microRNAs, the expansion of their universe, the cataloguing of their presence in the kingdoms of life, how they control gene activity and why this is so important, and finally how they are applied in science and medicine, we come to the end. Here, there is an opportunity to ask, ‘What’s next?’ What are some of the most exciting directions in current microRNA research and what lies over the horizon? This final chapter explores some of the latest questions. What is the totality of the influence of microRNAs in the most complex systems in the body and what technologies will we use or need to answer these questions? Are there components of the microRNA pathway still to be found? Some of the most advanced applications of microRNAs are in the field of synthetic biology, where microRNAs can be useful in engineered cells and systems. After such a richness of discovery about microRNAs during development, research is now asking questions about what microRNAs do towards the ends of our lives. Finally, a speculation about whether microRNAs or molecules like them exist beyond the borders of Earth, wherever else life is found in the universe.

In 2010, only a decade since microRNAs were discovered in humans, the first patient was treated with a microRNA drug, miravirsen, for hepatitis C virus (HCV) infection. This chapter opens with the discovery that HCV contained binding sites for miR−122, an abundant liver-specific microRNA. It looks at the research showing how the virus hijacks miR−122 to replicate, and the groundbreaking drug development programme that took advantage of this to create the world’s first medicine to target a microRNA. It covers some of the microRNA-based therapies further back in the drug development pipeline, discussing the relative strengths but also the risks of this approach. It explores the method to target microRNAs, including recent developments to disrupt single microRNA–target interactions to create precision microRNA therapies, and the viruses being commandeered to deliver microRNA treatments into specific cell types in the body. Lastly, it looks at how new microRNAs are being identified and considers the future of microRNA-based treatments, focussing on prospects for neurological disorders and reflecting on how, by listening to patients, we can create better and safer medicines.

In the years following FDA approval of direct-to-consumer, genetic-health-risk/DTCGHR testing, millions of people in the US have sent their DNA to companies to receive personal genome health risk information without physician or other learned medical professional involvement. In Personal Genome Medicine, Michael J. Malinowski examines the ethical, legal, and social implications of this development. Drawing from the past and present of medicine in the US, Malinowski applies law, policy, public and private sector practices, and governing norms to analyze the commercial personal genome sequencing and testing sectors and to assess their impact on the future of US medicine. Written in relatable and accessible language, the book also proposes regulatory reforms for government and medical professionals that will enable technological advancements while maintaining personal and public health standards.

Medical and forensic applications of recombinant DNA are described in Chapter 15. The range of genetically based diseases is outlined, and potential therapies discussed, covering diagnosis of infection, comparative genomics, development of vaccines, therapeutic antibodies and xenotransplantation. Treatment using gene therapy approaches is described, and the relatively limited success of gene therapy is considered in the context of its initial promise and the expectations that emerged from this. RNA-based therapies are covered by discussing RNA interference and antisense oligonucleotides, and the medical applications of genome editing are considered. The CCR5 controversy, known as the ‘CRISPR babies scandal’, is mentioned as an example of how the overall system can fail to prevent unethical practices when these are driven by determined scientists and clinicians. DNA profiling for analysis of DNA is described, and its use in forensic, legal and other applications is outlined.

Steps taken to start a new venture can make for rocky road ahead if consideration is not given to the points reviewed in this chapter. How to select and build a team and fairly distribute the founder’s equity, how to select an advisory board or a board of directors, and the importance of establishing a culture within the new company are all points discussed in detail and highlighted through personal stories and case examples. The main components of a business plan are covered in many texts and blogs, so this chapter focuses on the practical issues that few academic texts discuss, such as: how to perform due diligence on your investors and tips on creating slide decks , pitching and presenting business plans, and structuring financials and milestone to meet investors key concerns. The sources of financing and expectations of investors are reviewed with a view to guiding the entrepreneur or executive through the key elements for success, including successful closing on a term sheet or preparing for due diligence so that the process moves smoothly towards closure of the financing. The specific challenges facing an academic technopreneur moving into a decision-making executive (CSO or CEO) role are reviewed and guidance offered on utilizing the strength of the team around them.

From the long path through preclinical development, entering the regulatory field of interactions for human clinical trials can sometimes feel like you are walking into the lion’s den. This chapter guides you through an understanding of how to interact and how to prepare for FDA meetings so that they are on your side rather than fighting you. The common goals of companies and the FDA are highlighted here. Specific issues with identifying the appropriate regulatory approval pathway are discussed here with cautionary case studies. Complex new technologies which combine diagnostics and drugs, or devices and software, or AI-based dynamic software are reviewed here. The best approach to the appropriate regulatory pathway will be clear after reading this chapter. Case studies are used to show successful pathways taken by cutting-edge developments, such as cell-based therapy.

Human genome editing has become a reality and is here to stay. A logical question that follows, therefore, is whether the government should regulate the technology and, if so, what precise measures should be adopted to promote or hinder technological development. This chapter focuses on those questions at the intersection of human genome editing—specifically, germline genome editing (GGE) —and administrative law. The chapter highlights the FDA’s role as the agency in charge of protecting the public health by ensuring the safety and efficacy of human drugs and biological products, as well as shepherding scientific discoveries into the clinical realm. By examining precedents in gene therapy and stem-cell interventions, which are likely relevant to GGE, the chapter identifies regulatory gaps and proposes a novel regulatory framework for future GGE interventions. The chapter further frames the regulatory discussion in the context of an existing de facto legislative GGE ban, which prohibits the FDA from reviewing investigational uses of GGE technology in human embryos. Lastly, the chapter argues that the current legislative ban creates more societal costs than benefits, and it increases the likelihood that GGE technologies will be forced to develop in jurisdictions where regulatory systems may be inadequate from social and ethical standpoints.

In the chapter “The Biotechnology Sector – Therapeutics”, the author covers a wide range of topics summarizing the significant role that the formation and growth of the biotechnology sector has played in the entire biopharmaceutical industry. The chapter begins with a bit of history, from the earliest days of how genetic engineering gave birth to this sector, and takes the reader through an overview of biotechnology as it exists today and how the growing innovation in science over the years has been able to both drive the sector and have a tremendous impact on healthcare overall. There is a particular focus on describing various types of innovation which have played a huge role in driving product development in the broader biopharmaceutical industry. Later in the chapter, there is a focus on many of the business aspects of the sector, as drug development in biotechnology requires enormous amounts of capital for success. The author outlines many of the key issues related to different business and financing models that we see across the sector, in addition to the unique management issues in small biotechnology companies. There is significant description and explanation of the symbiotic relationship between the larger pharmaceutical companies and smaller biotechnology start-ups with a focus on how they help each other to bring transformative medicines to patients. The chapter concludes with a discussion about international and regulatory aspects impacting the sector. Overall the author tells the story of the birth and growth of this exciting sector, and its impact on patients and drug development over the last forty years, well substantiated with current data to build the case for how biotechnology today plays a major role in driving one of the most important and exciting technological industries of our time.

Sweden can be considered a relatively liberal European country when it comes to research, for example, it allows creating embryos for research purposes; yet, the question of human germline genome modification has been approached with great caution. With the adoption of the Genetic Integrity Act in 2006, the Swedish legislature intended to enable some research relating to gene editing technology while simultaneously placing bans on its use in clinical trials and clinical care, and providing criminal sanctions if these bans are violated. In this way, Swedish law is also aligned with its external commitments, and in particular, the EU Clinical Trials laws. While arguably the Genetic Integrity Act could have effectively functioned prior to the advances in gene editing technology, today it may be regarded as ambiguous and outdated. Hence, risks that ethically contested practices could emerge cannot be excluded. This chapter examines the national laws and policies relating to human germline genome modification in research and in clinical care in Sweden, with due regard to Sweden’s external commitments. Importantly, in light of the ongoing regulatory discussions at the national, European and international fora, it is not obvious that, should European laws become more permissive, and enable human germline genome modification, so would Swedish national law.