David Brown

Babraham Institute Enterprise

Fragile X syndrome is a neurodevelopmental disorder caused by silencing of the fragile X messenger ribonucleotide gene. Patients display a wide spectrum of symptoms ranging from intellectual and learning disabilities to behavioural challenges including autism spectrum disorder. In addition to this, patients also display a diversity of symptoms due...

Background Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomised, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods Adults with acute uncomplicated diarrhoea aged 18 to 70 were randomised to 4 groups: (A) loperamide; (B)...

Background: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomized, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods: Adults with acute uncomplicated diarrhoea were randomized to 4 groups: (A) loperamide; (B) loperamide a...

Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms has guided the choice of drugs for clinical trials,...

We are in the early stages of the Third Industrial Revolution. The three main factors that drive a new industrial revolution will be discussed, then the future scale of big data in healthcare will be analysed. Genomics and other healthcare data storage size could far exceed all other domains. Healthcare needs revolutionising, and it will be within...

Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-a...

- Phenotypic approaches dominated until 1990s, but had major weaknesses leading to high failure rates in human clinical trials. - Target-based approached were the adopted but often failed to solve the problems, and introduced new issues. - Can our new technologies applicable to drug repositioning overcome the weaknesses of these two old approache...

Some countries/ regions have had notable success in building hi-tech clusters, generating stable regional employment levels within high value growth industries. For future success, countries and regions need to understand two things: Historically, what factors have driven success in building Clusters of Innovation? For the future, as the Third I...

A fascinating presentation by Dr David Brown on how the world is already facing its third Industrial Revolution. The First Industrial Revolution started in the late 18th century with the mechanisation of the textile industry. The Second Industrial Revolution started in the late 19th century with mass production such as Ford assembly lines. But now...

Diarrhoea is the second leading cause of death in children globally. Just under 9 million children aged under 5 years died in 2008 and 1.5 million of these deaths were due to diarrhoea. It kills more children than AIDS, malaria, and measles combined. Including adult deaths, diarrhoeal diseases killed over 2.5 million people in 2009, according to th...

The switch in the mid-1980s/early 1990s from a phenotypic approach to a target-based approach to drug discovery has been followed by low productivity of new drugs entering the market. Reasons for the (necessary) switch and unsolved problems with both approaches to drug discovery are discussed. The S-curve theory of new technology development and in...

The number of new drug approvals per annum has been decreasing regularly over the past decade, and changes made 12 to 15 years ago to the research and development approach of the pharmaceutical industry may have contributed to this fall in productivity. In particular, the rapid switch at that time away from an 'observation-led' approach toward a 'h...

Advances over the past decade in drug discovery technologies have not yet led to an increase in productivity. We analyzed the reasons that have led to this juncture and identify the selection of the right target and the right lead as crucial. New approaches are required to take full advantage of the genomics revolution. For targets, methods are bec...

5-(2′-Alkoxyphenyl)pyrazolo[4,3-d]pyrimidin-7-ones, and in particular our preferred compound, sildenafil (VIAGRATM), discovered through a rational drug design programme, are potent and selective inhibitors of the type 5 cGMP phosphodiesterase from both rabbit platelets and human corpus cavernosum. Sildenafil is currently in the clinic for the oral...

A combinatorial library of 30,752 compounds has been synthesised from a set of 32 natural and unnatural amino acids. The library was designed to include the known endothelin antagonist, FR-139,317, as a positive control, and this and a number of close analogues were shown to be the most potent compounds. Thus, combinatorial libraries may be used bo...

A search for potent inhibitors of EC 3.4.24.11, an enzyme which is found most abundantly in the kidney and which degrades atrial natriuretic factor, has led to the identification of UK-69,578. Structure-activity studies starting from substituted N-carboxymethyl dipeptide inhibitors resulted in the introduction of a cyclo-alkane P1' residue and in t...