5 min readStem Cells Technology and NPOs in Drug Discovery

In the current economic gloom, it is very tempting to write another run-of-the-mill article about how the credit crisis is affecting the pharmaceutical industry and the healthcare domain as a whole. However, since those issues have been covered and belabored threadbare in most other journals, this article will focus on some of the other interesting things that are happening in the industry.

Stem Cells Technology for Drug Discovery: Another boon from these enterprizing cells
The hurdles faced by the drug discovery and pharmaceutical industry are now obvious to all; long R&D cycles and approval times, drug attrition and large clinical trial sizes, all of which lead to low productivity and low return on investment. Factors such as large clinical trial sizes and approval times are un-controllable by the pharmaceutical industry as these ensure the safety of the consumers and are a necessary evil of sorts. That said, the challenges that can be overcome with a lot of time and effort are those concerning drug attrition and R&D cycle times. Using better and novel drug discovery technologies, pharmaceutical companies could potentially address these problems.

That said, ever since the human embryonic stem (hES) cells were isolated in the late nineties, the field has been under great scrutiny and interest from several different groups of people such as scientists, bioethicists, pro-lifers and religious groups. Apart from tissue replacement therapies, which is the flagship application of hES cells, in recent years, these cells have also been under study for use in drug discovery research. Of late, the industry has realized that in order to prevent late stage attrition of drug candidates, it is very important to conduct extensive toxicity studies early on in the process and eliminate compounds with undesirable levels of toxicity. To do this, it is necessary to conduct expensive animal model studies which also suffer from issues of clinical relevance, ethical and political issues concerning the use of experimental animals. All these put together has led to industry-wide longing for alternatives to animal testing. One that is actively being explored is the use of hES cells for conducting safety and efficacy studies. There is a great need for efficient and robust physiological cell models and hES cells fit the prescription perfectly as they are pluri-potent, which means they have the ability to differentiate into virtually any type of cell and self-renew. In addition, they are also amenable to genetic modification which can be useful in improving the throughput and can help create specific disease models.

In spite of all the obvious advantages of the stem cell technology, progress has been slow in this field due to ethical issues surrounding it. The eight year ban that was enforced on hES cell research could possibly be lifted by the new US president Barack Obama. If this does ultimately happen, then the field will potentially advance at a much greater pace due to availability to federal funding and could lead to some tangible products in a few years down the line. In Europe, the situation is very complex as some countries such as UK, Sweden and Belgium are permissive to hES cell research while other such as Ireland and Austria are completely prohibitive on this technology. Like the US, the EU also only provides funding to hES cell research on existing cell lines due to the diversity of the laws of the different countries that comprise it.

Currently hepatocyte and cardiomyocyte cell lines are the ones that are widely studied due to their vast applicability, as a majority of diseases can be traced down to cardiomyocytes or hepatocytes. Hepatocytes are also of interest because they can be used to treat liver disorders which would otherwise require a complicated transplantation. That aside, more importantly from the drug discovery context, a good source of hepatocytes could also facilitate the development of new drug discovery strategies that could aid in performing in vitro toxicity assessments and metabolism studies. They help in studying effects of treatments for metabolic and dyslipidemic diseases. The applications of cardiomyocyte cell lines are mainly of two major categories. The first and obvious one is in the testing of drugs for cardiac diseases. The second and equally important application is for assessing cardiac safety of novel therapeutics. This is very important because regulatory agencies are very particular about cardiac safety data of any potential drug that may visit their offices for approval.

All the above said, it can be concluded that hES cell research holds great potential and promise for understanding and treating human diseases and disorders. Until the barriers for the use of these cells for transplantation to cure degenerative diseases are overcome, they can continue to help the field of drug discovery reap its benefits. Future direction of research in this field will be targeted towards improving the directed differentiation of hES cells and improving the yield of target cells through enrichment and selection techniques.

Non-profit Organisations: We need them in Drug Discovery
Another interesting area in drug discovery that has not been explored often but is worth looking at is the role of non-profit organisations in drug discovery.

Most of the major diseases that have high and wide prevalence are being dealt with by the pharmaceutical industry. The business model of this industry is such that it can only take up ventures that ultimately yield profits, considering the cost of discovering and developing a successful drug can be anywhere between $800 million and  $1500 million if the cost of failed drugs are worked into the equation. This then leaves out some diseases that will not yield any financial gain and these are now known as “neglected diseases” or “orphan diseases”. Most of these are tropical diseases that affect third world countries that cannot afford to pay for their treatment. Some examples of such diseases are tuberculosis, malaria, Dengue fever, trypanosomiasis, leishmaniasis, Buruli ulcer and diarrheal diseases. Sometimes AIDS is also considered among these because poor countries cannot afford Western medicines.

This leaves a very large unmet need which calls for new funding mechanisms. This is where non-profit organisations step in. Some of the government-funded institutions that are active in this space include the Small Business Innovation Research (SBIR) and the Small Business Technology Transfer (STTR) program of the US government, framework programs of the European Community, the Singapore Economic Development Board, the Innovation Promotion Agency (CTI) of the Swiss Science & Technology Council, to name a few. Some of the private institutions that actively fund orphan drug development programs, include the Wellcome Trust and The Bill and Melinda Gates Foundation (BMGF). These foundations not only fund these initiatives but also help by setting the agenda and priorities, giving strategic direction and providing resources in a manner that is unprecedented.

A new landscape has emerged of drug discovery consortia that bring together academic groups, industrial partners and donors, all of which aid in effectively addressing the largely unfulfilled medical needs of tropical diseases. This has given rise to three main instruments, namely non-government organisations (NGO) which form consortia to address a particular disease and fund the development of drugs for it through the pharmaceutical and biotechnology industry and academia, public-private partnerships (PPPs) and academic open source networks. Some examples of NGOs include the Global Alliance for TB Drug Development (GATB), Medicines for Malaria venture (MMV), Drugs for Neglected Diseases initiative (DNDi) and the institute for One-World Health (iOWH). A good example of a PPP is the Novartis Institute for Tropical Diseases in Singapore (NITD),

Academic, open-source networks driving drug discovery have come into being quite recently in order to organise drug discovery around a technology, a particular target or disease without any industrial partners. Examples are The Sandler Center for Basic Research in Parasitic Diseases, the tropical disease initiative at the University of Dundee and the Rosberg Institute.

There are inherent shortcomings in such loosely structured collaborative networks. These types of ventures are not as well structured as the corporate ventures due to unpredictable funding streams. Because of this, they are under even greater pressure than the pharmaceutical industry to embrace cost-cutting measures which is very challenging.

In spite of the above and several other setbacks, these instruments have achieved great success. One good example is Coartem, the first Artemisinin-based fixed dose combination therapy for malaria which was developed by Novartis in tandem with WHO. Such success stories instill confidence that tropical disease-stricked third world countries may still have hope.

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