Fostering collaborative research for rare genetic disease: The example of Niemann-Pick type C disease

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the “SOAR” mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders

THE FUTURE OF BIOTECHNOLOGY: ACCELERATING GENEEDITING ADVANCEMENTS THROUGH NON-EXCLUSIVE LICENSES AND OPEN-SOURCE ACCESS OF CRISPR-CAS9

From the immune system of bacteria comes a promising new gene-editing technology, CRISPR-Cas9. Discovered in 2012, CRISPR-Cas9 has already been named one of the fastest, easiest, and cheapest gene-editing technologies. With this reputation, CRISPR-Cas9 shows promise in the research and treatments of a wide array of diseases: cancer, blood disorders, blindness, AIDS, Cystic Fibrosis, Muscular Dystrophy, Huntington’s disease, and even COVID-19 to name a few. This relatively new technology has brought hope to researchers, doctors, and patients alike; however, current biotechnology licensing practices could hinder CRISPR-Cas9’s groundbreaking potential. This article examines common biotechnology licensing practices, specifically the practices of two of the largest CRISPR-Cas9 patent holders, The University of California, Berkeley and The Broad Institute of MIT and Harvard. After each institution’s respective CRISPRCas9 discovery, a lengthy court battled ensued to determine which institution discovered CRIPR-Cas9 first, and whether patent infringement existed. Eventually, both institutions were granted their desired patents and quickly ensured the future of their technologies by creating independent companies to control the licensing of CRISPR-Cas9 patents. This article refers to such companies as “surrogate companies” and explains the function of these entities as the gatekeeper of valuable patent rights through exclusive licenses. This article offers solutions to existing exclusive licenses without losing sight of the important relationship between research institutions and surrogate companies. Providing limited field-of-use licenses, rather than over-inclusive exclusive licenses of CRISPR-Cas9 patented technology, will ensure that a wider range of the human genome can be treated. Rather than merely scratching the surface of multiple therapies, limited licenses allow companies to focus on and thoroughly develop specific gene therapies. This reduces the risk of overlooking or under developing potentially life-changing gene therapies. This article goes further, suggesting that the biotechnology industry adopt an open-source access model like the one used in the software industry. Such a model could prove beneficial for companies looking to expand product offerings while still maintaining profits. Historically low-profit diseases, like tropical diseases, could become more desirable to companies based on the collaboration and reduced R&D costs inherent in open-source practices

A Scientific Roadmap for Antibiotic Discovery: A Sustained and Robust Pipeline of New Antibacterial Drugs and Therapies is Critical to Preserve Public Health

In recent decades, the discovery and development of new antibiotics have slowed dramatically as scientific barriers to drug discovery, regulatory challenges, and diminishing returns on investment have led major drug companies to scale back or abandon their antibiotic research. Consequently, antibiotic discovery—which peaked in the 1950s—has dropped precipitously. Of greater concern is the fact that nearly all antibiotics brought to market over the past 30 years have been variations on existing drugs. Every currently available antibiotic is a derivative of a class discovered between the early 1900s and 1984.At the same time, the emergence of antibiotic-resistant pathogens has accelerated, giving rise to life-threatening infections that will not respond to available antibiotic treatment. Inevitably, the more that antibiotics are used, the more that bacteria develop resistance—rendering the drugs less effective and leading public health authorities worldwide to flag antibiotic resistance as an urgent and growing public health threat

Impact of Biobanks on Research Outcomes in Rare Diseases：A Systematic Review

Rare diseases (RDs) are a global priority yet are still under researched. When combined, RDs are common, with individual diseases numbering approximately 5,000-8,000, equating to approximately 7% of the population in Europe. Extrapolating this figure for Australia suggests that about 1.2 million people are affected by RDs, with about 400,000 of those being children. The WA Rare Diseases Strategic Framework 2015-2018, the first strategy for rare diseases in Australia, recognises that in order to alleviate the significant burden of rare diseases, innovative translational tools that facilitate research into new diagnostic and therapeutic strategies should be given priority. Registries facilitate clinical, epidemiological, and post-marketing surveillance research for RD, collecting information from individuals with a particular disease, and storing these data in an organised system. Registries can lead to a greater understanding of the natural history of disease, consensus-driven treatment protocols, informed policy making and, in turn, improved patient outcomes. Despite these benefits, registries are limited in their capacity to conduct basic research, attributed to the fact that most registries do not collect and store patient and donor specimens appropriately to capture or preserve important biological information (such as DNA, RNA and proteins) for basic research, a prerequisite for translating scientific discoveries into diagnostic tools and therapies for clinical practice. Biobanks (BB) are gradually becoming more recognised as invaluable tools to drive basic and translational research for RDs. BBs collect and store biological specimens with matched clinical data and patient metadata in an organised system, distributing samples and data to the scientific community, enabling “omics” studies. This is especially important considering the field of drug innovation for RDs has, in recent years, become progressively focused on ‘omics-type research, and that more than 80% of RDs have a genetic component RDs have recently been referred to as “fundamental diseases”, highlighting their unique capacity in providing opportunities to investigate the “extremes of human pathology”. For example, research of LDL-receptors in familial hypercholesterolemia, a rare disease, led to the discovery of statins, a drug therapy that is now also routinely used to prevent heart disease. This Masters research thesis examined the research outcomes of two specific research strategies: registries linked to BBs and registries without BBs, and found that whilst registries without BBs had the capacity to uncover the natural history of disease, develop best practice, replace clinical trials, and improve patient outcomes, they were limited in their capacity to conduct basic research. Registries, when annexed to BBs, had the key infrastructure required to make novel Omics discoveries, identify and validate biomarkers, uncover novel genes, and develop new therapeutic strategies. The results of this Masters research thesis suggest that the role of basic research in RD research is vital; scientists must first understand the pathways of disease before they can develop appropriate interventions. Linkage of BBs to RD registries will provide the enhanced resources required for the effective translation of basic research into clinical practice

A new solution suggesting the need for a new equation

When Victoria Hale first came up with the notion of starting the Institute for OneWorld Health (iOWH), some cautioned that the idea of a non-profit pharmaceutical company developing drugs to treat neglected diseases was a proven loser. The more direct among them might also have inquired why a successful scientist, trained in being analytic, consistent and logical, would undertake such an evidently hopeless project. Yet a few years later, iOWH has not only achieved its first drug approval (i.e. Paramomycin for the treatment of leishmaniasis or ‘black fever’, approved for use in India), it has also seen that same drug included in WHO’s Essential Medicines list, and has research results in the New England Journal of Medicine. This turnaround raises a question: Did skeptics fail to grasp Hale’s clever insights, misjudge the depth of her commitment, or underestimate the extent of her potential good fortune? Put more simply, is Hale’s a story of smarts, guts, and luck

Clinical Translational Science 2020: Disruptive Innovation Redefines the Discovery-Application Enterprise

Vaccines, analgesia, and antibiotics embody some of the most enduring therapeutic breakthroughs that have transformed medicine. Building on such fine paradigms of biomedical innovation, the evolution of technologies has increasingly sparked spectacular advances across the continuum of wellness and disease-spanning medical and surgical specialties. Discovery science—fueled by government and private sector resources—has systematically instituted the principles of modern healthcare delivery ensuring that medical practice is based on up-to-date scientifi c evidence. Th e harmony between science, technology, and resources has culminated in a golden age of discovery and translation, eradicating infections, curing cancers, and palliating endocrine and metabolic diseases. Indeed, proven therapeutic and preventive approaches have progressively moved into everyday practice

Health sector reforms in Central and Eastern Europe

The political and economic transition of the 1990s in the countries of central and eastern Europe has been accompanied by wide ranging health care reform. The initial Soviet model has given way to a variety of forms of health insurance. Yet, as this paper argues, reform has too often been preoccupied with ideological imperatives, such as provider autonomy and the creation of funds separate from government, and has given much less thought to the contribution that health care can make to population health. The paper begins by examining the changing nature of health care. It recalls how the Soviet model was able to provide basic care to dispersed populations at low cost but notes how this is no longer sufficient in the face of an increasingly complex health care environment. This complexity reflects several factors, such as the growth in chronic disease, the emergence of new forms of infectious disease, and the introduction of new treatments requiring integrated delivery systems. It reviews evidence on how the former communist countries failed to keep up with developments in the west from the 1970s onwards, at a time when the complexity of health care was becoming apparent. It continues by setting out a framework for the organisation of health care based on the goal of health gain. This involves a series of activities that can be summarised as active purchasing, and which include assessment of health needs, designing effective packages of care, and monitoring outcomes. It concludes by arguing that a new relationship is needed between the state and the organisations involved in funding and delivering health care, to design a system that will tackle the considerable health needs of the people who live in this region.Central and Eastern Europe, Europe, health, health care reform, population health

Driving a decade of change: HIV/AIDS, patents and access to medicines for all

Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines

Outbreaks Reveal Deficiencies In Biotech R&d For Emerging Diseases

The absence of commercial diagnostics, therapeutics, and vaccines hindered control efforts during the recent Zika and Ebola epidemics. This study evaluates the connectivity and productivity of both viruses’ R&D networks before, during, and after the epidemics to ascertain the ability of current R&D practices to support the development of crucial biotechnologies. Both network maps exhibited low baseline connectivity with emergent collaborative R&D practices during the identified outbreak period that correlated with increased research productivity. It is argued that formally establishing permanent collaborative, open R&D practices prior to epidemics can enhance scientific knowledge and innovation capabilities to more effectively advance commercial availability of diagnostics, therapies, and vaccines for emerging diseases