Researchers find using genetic association data applied to drug target selection could significantly boost success rate

July 1, 2015 by Bob Yirka, Medical Xpress report

Credit: Susan Buck Ms/Public Domain
(Medical Xpress)—A team of researchers with member affiliations to institutions in the U.S. and Hong Kong, has found that researchers going after drug targets that have supporting genetic evidence could double the success rate of new drugs making it through clinical trials. In their paper published in the journal Nature Genetics, the team describes how they correlated data from gene associated disease databases to drug development databases to find commonalities.

Developing to treat diseases is a risky venture—currently approximately half of those approved for clinical trials fail to deliver on expectations. Because a lot of time and effort goes into , those that fail can represent a significant loss. Finding a way to improve the odds would help both the bottom line of drug developers and the human beings who eventually benefit from the drugs that pass through the system. In this new effort, the researchers believe they have found a way to do just that—by taking into consideration gene associations as part of pursuing a given target.

The team accessed data from GWASdb—where information about common diseases with a genetic cause is stored, along with data from the Online Mendelian Inheritance in Man database—it houses more rare genetically based diseases. After mapping that data to Medical Subject Heading, they came up with a group of 16,459 gene and trait combinations. Next, they pulled data from the Informa Pharmaprojects database, which houses information about drugs making their way from research to use by patients. Finally, they set a benchmark of a successful drug to mean one that passed and was okayed for use in the U.S. or European Union.

In looking at the connection between gene associations and drug targeting, they found that those drugs that were a success more often targeted genes with evidence of association to a disease. So strong were their results that the team is claiming that using their approach could double the success rate of drugs under consideration. They noted too that using such associations proved to be more advantageous with some genetically based disease than with others and that the improved rate varied depending on the phase of the clinical trial.

Explore further: Biological markers increase clinical trial success rate of new breast cancer drugs

More information: The support of human genetic evidence for approved drug indications, Nature Genetics (2015) DOI: 10.1038/ng.3314

Abstract
Over a quarter of drugs that enter clinical development fail because they are ineffective. Growing insight into genes that influence human disease may affect how drug targets and indications are selected. However, there is little guidance about how much weight should be given to genetic evidence in making these key decisions. To answer this question, we investigated how well the current archive of genetic evidence predicts drug mechanisms. We found that, among well-studied indications, the proportion of drug mechanisms with direct genetic support increases significantly across the drug development pipeline, from 2.0% at the preclinical stage to 8.2% among mechanisms for approved drugs, and varies dramatically among disease areas. We estimate that selecting genetically supported targets could double the success rate in clinical development. Therefore, using the growing wealth of human genetic data to select the best targets and indications should have a measurable impact on the successful development of new drugs.

Related Stories

Biological markers increase clinical trial success rate of new breast cancer drugs

October 1, 2012
Using biological markers—genetic characteristics that are associated with some patients with breast cancer—can increase the success rate of clinical trials for breast cancer drugs by almost 50 per cent, says new research ...

Most information in drug development is lost

March 9, 2015
Lots of potentially useful medical information is getting lost. McGill researchers discovered this when they looked into the lack of reporting of information from "stalled drug" trials in cancer, cardiovascular and neurological ...

Drug-target database lets researchers match old drugs to new uses

May 22, 2014
There are thousands of drugs that silence many thousands of cancer-causing genetic abnormalities. Some of these drugs are in use now, but many of these drugs are sitting on shelves or could be used beyond the disease for ...

Database of disease genes shows potential drug therapies

October 13, 2013
Researchers at Washington University School of Medicine in St. Louis have created a massive online database that matches thousands of genes linked to cancer and other diseases with drugs that target those genes. Some of the ...

Randomized controlled trials must be simplified to sustain innovation

June 15, 2015
Randomised controlled trials must be simplified to sustain innovation in cardiovascular diseases, which are still the biggest killer in Europe, according to the Cardiovascular Round Table (CRT).

Ethics experts call for more thoughtful optimization of drug development process

May 9, 2013
(Medical Xpress)—McGill University post-doctoral fellow Spencer Phillips Hey and Prof. Jonathan Kimmelman, Biomedical Ethics, Social Studies of Medicine, Faculty of Medicine argue that some clinical trials of new drugs ...

Recommended for you

Researchers uncover molecular mechanisms linked to autism and schizophrenia

December 13, 2018
Since the completion of the groundbreaking Human Genome Project in 2003, researchers have discovered changes to hundreds of places in the DNA, called genetic variants, associated with psychiatric diseases such as autism spectrum ...

CRISPR joins battle of the bulge, fights obesity without edits to genome

December 13, 2018
A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper published Dec. 13, 2018, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used ...

Noncoding mutations contribute to autism risk

December 13, 2018
A whole-genome sequencing study of nearly 2,000 families has implicated mutations in 'promoter regions' of the genome—regions that precede the start of a gene—in autism. The study, which appears in the December 14 issue ...

New method for studying ALS more effectively

December 13, 2018
The neurodegenerative disease ALS causes motor neuron death and paralysis. However, long before the cells die, they lose contact with muscles as their axons atrophy. Researchers at Karolinska Institutet in Sweden have now ...

Paternal grandfather's high access to food may indicate higher mortality risk in grandsons

December 12, 2018
A paternal grandfather's access to food during his childhood is associated with mortality risk, especially cancer mortality, in his grandson, shows a large three-generational study from Stockholm University. The reason might ...

New genetic study could lead to better treatment of severe asthma

December 12, 2018
The largest-ever genetic study of people with moderate-to-severe asthma has revealed new insights into the underlying causes of the disease which could help improve its diagnosis and treatment.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.