Drug Development Doesn’t Always Have to Start From Scratch
Article Jun 05, 2017 | Simon Pearce, Market Segment Manager for Organics, with Thermo Fisher Scientific
Bringing a new drug to market is an expensive and time-consuming process, typically taking over a decade and with an associated cost of around 2.6 billion US dollars, according to a recent report by the Tufts Center for the Study of Drug Development. With increased pressure from generics, price controls and a drug discovery pipeline that’s run dry, it’s little wonder that pharmaceutical companies are looking for quicker and more cost-effective ways to turn a profit.
One strategy that’s being increasingly adopted by the industry involves repositioning existing drugs for new therapeutic purposes. With the recent discovery of a potential dementia treatment based on repurposed molecules previously developed to treat other disease classes, we look at how developers can use screening libraries to bypass many of the stages involved in drug development and access the untapped potential of existing drug molecules.
A shortcut to a groundbreaking dementia treatment
With life expectancies on course to increase by two-and-a-half years every decade, age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s are set to become a significant problem for global health – and a growing market for the pharmaceutical industry.
A major factor in the development of neurodegenerative disorders such as dementia and prion diseases is the accumulation of misfolded proteins in the brain. The build-up of these misfolded proteins can trigger a biological response which effectively ‘switches off’ the essential production of new proteins which is thought to lead to memory impairment and neuron loss.
In groundbreaking research reported in 2013, a UK Medical Research Council team prevented the neurological signs of prion disease in prion-infected mice by reactivating protein production using an experimental drug. However, the compound was subsequently found to cause pancreatic damage in humans and did not progress to clinical trials.
Learn more: ground-breaking dementia drug
However, after screening over 1,000 molecules from the National Institute for Neurological Disorders and Stroke (NINDS) compound library, the team have now identified two existing drugs that show similar neuroprotective effects. The findings, published in the journal Brain, show that the repurposed drugs prevented the emergence of brain cell damage in mice with prion disease, and restored memory in mice possessing a form of dementia.
One of the two drugs, trazodone hydrochloride, is a licensed antidepressant already available on the market. The other, dibenzoylmethane, has already shown minimal side effects in mice and is currently in clinical trials as an anti-cancer drug.
Read more: MRC researchers re-purpose two drugs to stave-off dementia
The fact that trazodone is already safe for use in humans may help to accelerate its progress through clinical trials, with the team hoping to find out whether the drug is effective in dementia patients within the next three years.
Simplifying the search using high-quality screening libraries
Taking drugs that have been developed for the treatment of one disease and using them to tackle another is a strategy that is being increasingly deployed within a pharmaceutical industry that’s finding R&D budgets squeezed. This approach can bypass much of the time and resource-intensive development process, and give manufacturers added confidence that a drug will demonstrate the favorable pharmacokinetics and low toxicity necessary to clear clinical trials.
One of the best ways of finding new therapeutic treatments is through the use of high-quality screening libraries, that can be used to screen a diverse range of existing drug structures and commonly used scaffolds against new disease targets.
Compounds containing heterocyclic moieties, just like trazodone, are extremely important in drug discovery. In fact, 64 of the top 100 drugs possess heterocycles in their structure. A comprehensive collection of these drug structures and commonly-used scaffolds are available in research quantities from companies such as Thermo Fisher Scientific, via their Alfa Aesar and Acros Organics brands. The use of compound libraries with a strong focus on these types of substructure can therefore be a very effective and efficient way of finding new or existing drug molecules for new disease treatments quickly, and within a limited screening budget.
Who says you can’t teach an old drug new tricks?
These latest findings demonstrate that the search for effective drug molecules doesn’t always have to start from scratch. Using structurally diverse compound libraries possessing a good selection of heterocyclic structures, pharmaceutical companies can perform repurposing screens to get more out of the compounds that have already proven to be safe to use in one disease area, and could show promise for use as alternative treatments in others.
A significant minority of major depressive disorder patients don’t respond to currently available antidepressant medication. A newly approved treatment, based on the "club drug" ketamine, could change that. In a session at the British Neuroscience Association’s Festival of Neuroscience 2019, the potential mechanisms of ketamine’s antidepressant action were put under examination.READ MORE
Given the complexity of cancer, it’s arguably unlikely that single molecules will work as clinically meaningful biomarkers for cancer. Today, biomarker discovery involves detecting patterns – characteristics or phenotypes that can be measured and monitored throughout a patient’s journey. Here, we look at two approaches being explored in this evolving field.READ MORE
When developing diagnostic tests or evaluating results, it is important to understand how reliable those tests and therefore the results you are obtaining are. By using samples of known disease status, values such as sensitivity and specificity can be calculated that allow you to evaluate just that.READ MORE