Outbreak of E. coli O104 (VTEC) Strain

E.coli, the bacteria - habitat of every human gut, has now suddenly turned to be man’s greatest enemy. This organism from time known has been a part of every scientific study. This was the first organism whose genetic data was decoded and became the basis for further genetic study. Being the easily understood organism and easily modifiable one, E. coli has been a part of the microbiological lab for understanding the genomics of many other complex microorganisms. The genetic material, DNA of the organism of interest is induced into E. coli and grown. The fast reproducing property of E. coli helps the production of the required gene or protein as desired for further study. E. coli strains have also known to cause mild illness to humans that are easily curable without or in certain cases without any medication. Nothing so far has known to be fatal. But the new strain of E. coli, has been causing an illness that may have a cure in the future, but is currently fatal.

How can an organism, that has been used as an assistance for the study for identification of many drugs, become life-threatening?

New strains of an organism are usually a mutated version of the basic known organism. If this strain of E. coli is a new strain of the organism, it just means that it either has some gene added, modified or removed from the original genomic code. And this change is leading to the production of toxin in the human body. The other note worthy fact in this outbreak is the easy spread or entry of the organism into human body. Having been a native of our body, the organism seem normal to the body’s immune system until it enters the stomach and begins to produce toxins.

Instead of trying to study this new mutant entirely, a quicker approach would be to establish a match between this version of E. coli and the possible organism that have a similar gene coding and similar symptoms. There might be a treatment in place for the other organism, which can further be studied, modified and administered as a solution to this deadly outbreak.

Collaboration between Academia and Industry Giants for Optimisation of Drug Discovery Efforts

The current trend in the pharmaceutical industry for drug development has been, to work solely on a project/drug. The companies hired people to develop a drug right from the scratch and this have resulted in loss of resources and also time. This method was probably adopted to ensure complete privacy on the current development in the organisation and to avoid competition, but they missed the fact that there was duplication of work occurring within the industry and academia. This also resulted in some of them working on a target that was already studied and found not to be useful.

In a meeting in Toronto, Canada on the 16th February 2011, that had attendees from the industry, academia and funding organisations, Chas Bountra, mentioned that the main drawback in the current methodology of the drug development was the parallel work being carried out in the industry. He is trying to get a method in place that would reduce the duplication.(LINK1, LINK2)

Now these giants are being advised to assign the basic research and study work to academia or smaller organisation, allowing them to concentrate on trails and development of the drug (some already following it). This is result in quicker and successful deliver of these medicines to the public.

The model proposed by Chas Bountra, head of the Structural Genomics Consortium(SGC) at the University of Oxford, UK, looks at the collaboration between the large companies and academia. In this scheme, academia plays a crucial role during the initial stages.  The initial research carried out by the academic scientist would be funded by both funding organisations and the pharmaceutical industry. The large companies would compete for the successful drug candidates at the later stage of drug development.

Such similar schemes are being discussed in many parts of scientific research. many government funding bodies are trying methods that would increase the return on the investment in research. How beneficial the outcome of such schemes would be to the people waiting for treatment, is something to wait and watch.

Recent Drug Development

In recent times, there have been reports of new drug targets being identified, for diseases that seemed to have no cure. Diseases that were life threatening, with no treatment available, seem defeat-able now.
Recent article in Drug Discovery and Development, highlighted the work of a Howard Hughes Medical Institute investigator, Leonard Zon. The investigator has identified new modes of therapy for an aggressive cancer, Melanoma, with Zebrafish as a model. Melanoma is the most dangerous type of skin cancer, that is known to consistently elude treatment. Various modes of treatment have been used to cure it, but like in most treatment, there is enormous amount of side effects. After intensive study, Zon and his team identified that a rheumatoid arthritis drug, Leflunomide, was able to hinder the growth of the cancer causing cells by changing the cell lineage. Zon’s group combined a BRAF inhibitor (a drug in late clinical trial stages for metastatic melanoma). Combining BRAF inhibitor, a drug specifically targeting oncogenic mutation, with Leflunomide led to marked decrease in melanoma in mice. This combination may enter human clinical trial within a year, advantages being usage of lower doses and reduced risk of side effects and resistance.
Another recent development is the identification of a target protein for Tuberculosis vaccine by scientists at Imperial College London. As we all know, TB is another dangerous disease that is difficult to cure. Approximately about 2 million people die each year due to this bacterial disease. The current vaccine, BCG vaccine, is not very effective and hence, it is essential to find a more effective cure to this. The result of the study conducted by the scientist, which is yet to be published, reveals that the protein EspC, which is secreted by the bacterium. Its high specificity to the organism and the strong immune response it provokes, makes it a promising target for a new TB vaccine. This gives hope for the development of a stronger and broader immunity against TB, than BCG. This protein is an addition to the 2 other targets that have been identified for development of a new TB vaccine.
The results of the intensive research for identification of new therapy and drugs for such dangerous disease looks very promising, but the question is when do we get to see the results. The development of these into final products, that can be used for treatment is slim and the timeline is enormous. This doesn't mean we can or should stop the research. It only means that we need to identify ways, where these developments can be converted into fruitful results ina faster manner. With technological developments, it has become easier for us to minimise the failure at the clinical trials stages of drug development. It is necessary that we utilise these technologies and make higher percentage research productive.

Patent Laws - Boon or Bane?

Are the Patent Laws a boon or a hindrance to current development and innovation? In the countries where patent laws apply, it takes a long time to process a patent application. The delay in processing leads to backlog in applications. Is this increased wait time holding back innovations?

The main reason for the delay in processing the application is that when the original patent laws were written, in the late 19th century, not many large scale innovation were seen in the industry.  But, does this mean, the industry was better off without the patent laws. People the industry feel that though the patent system is not perfect, it is definitely better than not having one. 

A snippet from a Guardian article - Speaking at the London School of Economics Mr. Steve Ballmer said  - "Is the patent system perfect, or the world in which we live? Answer is of course not, the patent law was crafted in a day and age that preceded modern IT systems" referring to the 2 biggest sectors that use patent laws. The pharmaceutical and IT industry, which are the 2 biggest sectors that use patents have shown tremendously growth in recent times. The innovation in these sectors demand the need for quick processing of patents. This calls for a reform in patent laws. Patent laws in US and Europe need to be rewritten to get in line with the latest technology developments. Countries like India and China need to get stringent patent laws in place, to encourage blooming start-ups. 

Recent article dated 28th February 2011, in Drug Discovery and Development, speaks about the reform in Patent laws. The long overdue reform in the law has finally shown a promising outcome. The Senate is taking up the Patent Reform Act, that transforms the 1952 Patent law radically, bringing the law matchable to current technology. With such reforms and proper changes to the patent laws, making it relevant to current development, the patent laws will continue to remain a boon to innovation and further development.

HIV Drugs and Patent Laws

In my earlier blogs, I spoke about the options of developing novel drugs for HIV AIDS, one of the fatal diseases threatening human life. More than developing drugs, it is important to ensure that the drugs reach the patients. But are the drugs reaching all the patients?

Patent laws give Multinational pharmaceutical organisations sole authority for production of novel drugs. giving them the sole right to develop and sell the drug. MNC’s sell the patented drugs at much higher prices, leaving treatment unaffordable to the poorer sector. Though the cost the MNC's quote for the drug is justified keeping in mind the cost incurred in R&D of these drugs, it remains a dream for many.

Even if other pharma companies manage to identify the composition of the new drug, they cannot develop generic drugs as it is patented. This guarantees the sales and increases profits for the patent holding organisation in return for their investment.

Recent news on NDTV, reported that Indian government refused to grant Abott the patent for 2 second phase HIV drugs. It is obvious that this is a great news for the pharma companies that work on generic drugs. But the real point of discussion is whether it is an advantage or disadvantage to the patients who are suffering? Is this going to make HIV treatment available to all, or is it still going to be unaffordable?

Alternate approaches to HIV treatment

In my earlier blog, I had written about alternative approaches of drug discovery for HIV infections. I recently read a blog about engineered E.coli that could solve Sudoko puzzle, (of all things !!!!). The writer feels that the organisms used in the experiment can no longer be called bacteria or virus due to the huge amount of engineering done to them. This made me think if it was possible to use such engineered organisms to tackle the HIV challenge.

All of my ideas are currently in a theoretical stage. I feel that further study and research into these arenas will reveal a promising solution to the HIV situation.

HIV Treatment - Integrase as target

The mutations in HIV leading to drug resistance has made treatment of HIV-1 infection challenging. I wonder, if alternative approaches can be explored to control HIV infections and simultaneously handle the mutations issue.

In my opinion, HIV-1 Integrase is a better target than Protease and Reverse Trancriptase, the other two viral enzyme. The lack of human homologue and the vital role the enzyme Integrase plays in the development of HIV, leads me to this opinion. Raltegravir and Elvitegravir, the two drugs developed to control HIV by targeting the Integrase enzyme have been somewhat successful in controlling the virus. However, the rapid rate of mutations in HIV has resulted in the organism building resistance to these drugs as well.

I am mulling the possibility of developing a drug that can inhibit the integration of viral DNA with the target DNA by blocking the target DNA’s availability. I am assuming that the failure of integration and further replication of the viral DNA should lead to the disintegration of the virus. The challenge here is to identify a methodology that would release the target DNA when the viral DNA is disintegrated and make sure that there is no viral DNA left to integrate to the released Target DNA.

I am sure there are others out there who are already working on these thoughts, and I would love to hear your opinion.