Repurposing Old Drugs for CFS

Deftereos-SpyrosWith approximately 6,000 approved drugs on the market here and in Europe for thousands of diseases, you’d think at least a handful would prove effective for chronic fatigue syndrome (CFS). Well, that’s exactly what the Solve ME/CFS Initiative’s grantee Biovista hopes to find by identifying existing drugs ripe for “repurposing.”

The concept of repurposing drugs is not new. Existing drugs are used “off label” all the time, particularly for cancer. That’s because once drugs are approved for one use, doctors are free to use them for other conditions. For instance, antidepressants, narcotics and amphetamines are often used off label to manage CFS symptoms such as fatigue, “brain fog” and unrefreshing sleep. None, however, address the disease holistically, leaving patients still suffering and still searching for relief.

Another example is rituximab, a drug approved to treat cancer and rheumatoid arthritis that is being studied in CFS after a research team in Norway noted its benefits in patients who had cancer and CFS.

Repurposing, however, goes a step further than the hit-and-miss approach of off-label use: systematically assessing every known aspect of a compound, whether approved or failed, for its potential to treat other diseases.

For instance, the erectile dysfunction drug Viagra began life as a possible treatment for hypertension, while thalidomide, a morningsickness drug banned in the early 1960s after it was found to cause horrible birth defects, was reborn in 2006 as an effective treatment for the bone cancer multiple myeloma.

The process of drug repurposing, also called “drug repositioning,” can slash the time and cost to bring new therapies to the patients who need them most, says Biovista vice president for drug discovery Spyros Deftereos, M.D., Ph.D.

Biovista is one of the leaders in the drug repurposing field. The Charlottesville, VA-based company has a systematic process that identifies the potential of existing, approved drugs for other medical conditions. As Biovista co-founder Aris Persidis, Ph.D., says, “A drug that is well seasoned is an excellent starting point for innovation.”

The grant request to the Association came after several discussions with Association staff, said Dr. Deftereos. “We thought it would be interesting for both parties,” he said. In addition, the neurological impairment and neurology-related mechanisms thought to be involved in CFS, particularly dysfunction of cellular mitochondria (the so-called “power house” of the cell), are right in line with other Biovista research. The company already has two drug candidates for another neurological condition, progressive multiple sclerosis, as well as candidate drugs for brain cancer, thyroid cancer and melanoma.


Dr. Deftereos and the Biovista team.

With its grant, Biovista will identify drugs that target what is known so far about the underlying biological dysfunction, or pathophysiology, associated with CFS. Investigators will also search for drugs that could resolve the symptoms of the syndrome, particularly CFS-related cognitive impairment and unrefreshing sleep. However, they will also explore potential therapies against other CFS-related symptoms, ideally finding drugs that can treat more than one symptom.

Three-Step Process

The repurposing process begins with the company’s proprietary software, the Biovista Clinical Outcome Search Space (COSS) drug repurposing platform. The software conducts a comprehensive search of numerous biomedical databases to identify potential compounds for further assessment, searching for linkages between genes and proteins implicated in the biological pathways of a disease. If diseases share such molecular pathways, then a drug that works in one might be effective in another. Dr. Persidis once likened the process to “eHarmony for medicine.”

“That’s why we can navigate all 23,000 diseases and all 6,000 adverse events against all 20,000 human targets and 95,000 drugs and pharmacologically active compounds with reasonable data in the public domain,” he told a reporter from The Scientist magazine.

WSJThen, using a proprietary algorithm that assesses 25 different components to identify every known gene, pathway, disease, anatomical location, cell structure and other component of potential drugs, including why and how they succeeded or failed, as well as potential side effects and drug/drug interactions, researchers develop a list of relevant drugs that should be further investigated.

The next step is to rank the identified drugs and make predictions about their potential benefit for CFS. The predictions are based not only on potential benefits, but also on safety profiles, potential interactions with other drugs already used to treat CFS, pharmacological characteristics (such as how long the drug remains in your system, any potential liver or kidney concerns) and their overall relevance to the underlying disease processes.

So far, the company has a 70 percent success rate in matching its predictions of drug activity against a given disease to actual efficacy. Its success is so good, in fact, that pharmaceutical giants such as Pfizer, Novartis and others have hired it to repurpose several of their existing drugs.

Finally, Biovista will use the Association’s SolveCFS BioBank to identify sets of biomarkers and clinical characteristics that can be used to validate the potential of the identified drugs to treat the syndrome and/or its symptoms.

The entire project should span 11 months. Ideally it will be followed by the design and launch of follow-up research and development work, either by Biovista, pharmaceutical companies, or research support organizations like the Association.

The ultimate goal: New drugs that target not only the symptoms of CFS, but the underlying disease process, possibly leading to the holy grail of effective treatment and, ultimately, a cure.

Read more about drug repurposing from The Scientist:
Amy Dockser-Marcus at the Wall Street Journal wrote about this project on February 23, 2012, as the Research Institute Without Walls was announced:

Dr. Deftereos’ project is funded under the Solve ME/CFS Initiative’s Research Institute Without Walls (RIWW). We are grateful for the support of donors to the Catalyst Fund that fuel research projects like this one and others linked under the RIWW. Your donation of any amount will help sustain important research aimed at identifying better diagnostics and treatments for CFS. Our secure online donation center is available 24/7. Thank you for your interest and support!

June 15, 2012