Pharma Strategy Blog

Stem cells and multiple sclerosis

"For the first time, some of the disability associated with the early stages of multiple sclerosis appears to have been reversed.  The treatment works by resetting patients' immune systems using their own stem cells."

New Scientist

Well, that paragraph certainly caught my eye this morning in the news, thanks to a friend for sending the link over. 

My initial thoughts were two fold - I liked the idea that stem cell technology might possibly help people with MS since I have several friends who suffer from the debilitating condition, but it tempered by the phrase 'resetting patients immune systems'.  Regular readers of this blog will be familiar with the disastrous TGN 1412 trial at Northwick Park, which has been covered here previously see here and here.  That study warned of the dangers of stimulating a normal immune system in homeostasis.

Let's take a look at multiple sclerosis though.  It's an autoimmune disease where the fatty myelin sheath, which wraps around nerve cells and speeds up their rate of transmission, is attacked by the body's own immune system.

Previous efforts with stem cells have tried to reverse that process with no success.  The researchers decided that perhaps waiting until advanced disease when neuro-regeneration had set in was the problem.  The next logical approach was to therefore look at early stage disease before the body is under attack.

21 people with early relapsing-remitting MS who had not responded to treatment with the standard drug, interferon beta, after six months received an autologous stem cell transplant (aSCT).  The patients had stem cells removed from their bone marrow, then receive chemotherapy to destroy all existing immune cells in the body, before re-injecting the stem cells.  The stem cells then developed into naïve immune cells that do not see myelin as alien, and hence do not attack it.

Three years later, 17 of the patients had improved by at least one point on a standard disability scale, while none of the patients had deteriorated.  The study has just been published in The Lancet Neurology.

The authors concluded that:

"Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial."

I have to say that realising the patients received a stem cell transplant rather than some immune stimulant reassured me greatly.  However, SCT is not a walk in the park - it is a known curative treatment for some forms of leukemia, but because it involves wiping out all the existing white blood cells, it weakens the patient and some die because they are unable to fight infection.

Interestingly, the patients received alemtuzumab as part of their SCT regimen, similarly to the Cambridge patients reported in the Guardian article highlighted below.  Alemtuzumab is a monoclonal antibody approved for the treatment of leukemia, but it became a candidate for MS when it was realised that it dampens the immune system.

Larger scale trials are still needed to confirm the initial results, but so far it looks a promising approach for the treatment of early stage MS.

Sources: R BURT, Y LOH, B COHEN, D STEFOSKY, R BALABANOV, G KATSAMAKIS, Y OYAMA, E RUSSELL, J STERN, P MURARO (2009). Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study The Lancet Neurology DOI: 10.1016/S1474-4422(09)70017-1

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Digital thoughts and playmaking in Pharma

Yesterday saw me taking a day trip to Washington DC for the SCIP DC meeting on "New Ways of Knowing 2.0" run by the admirable August Jackson.  This event was a workshop format and included brief overviews from Suki Fuller and Eric Garland.

For those interested, you can follow the synopsis and live Twittering of the event using the #scipdc code in Twitter search.  The discussion was lively and the audience, from a variety of fields, were engaged and interested to learn about new tools and ideas that they could apply to their competitive intelligence work.  There was, inevitably, a large focus on Twitter, what it is and how you can use it effectively.

For me, I was curious to see how many other Competitive Intelligence professionals are using social media and cloud tools in their workflow and to gather relevant data.  There was also a bonus as several interesting ideas cropped up during the workshop and stimulated my own thinking further.  The first was asymmetry of information, the second was playmaking and how both can influence marketing strategy.  These ideas piqued some long lost thoughts I had from reading some excellent books such as Daniel Pink's 'A Whole New Mind' about how right brain thinking will dominate in the information age and Don Tapscott's treatise on 'Grown up Digital'.  If you haven't read either book, I would highly recommend them. 

Much of the discussion yesterday kept circulating back to the impact of Gen X/Y versus Baby Boomers, and how the latter are often stuck in traditional models such as SWOTs, Porter's 5 Forces etc, whereas those from the Digital Age are more likely to embrace new ideas and the use of technology in ways the Boomers could never imagine:

"The bottom line is this: if you understand the Net Generation, you will understand the future.' And as my son often reminds me, the future is now."

Don Tapscott, Grown Up Digital

The digital age is indeed a-changing the landscape.  Just as breaking news is rapidly changing with community and citizens snapping events as they happen in real time on their iPhones, in many ways, CI is also at the forefront of this vanguard.  August, Suki and Eric demonstrated this with their adoption and use of cool new internet tools to help them find and process relevant information then analyse and shape it into a story or pattern that enables the user to recognise data to support a notion of strategic analysis and intent.  Ultimately, valid reliable information, whether gleaned from traditional market research or online tools, is key because it allows you to forecast and shape the future. 

The big question is can you gain a competitive advantage and do it faster and quicker than your competitors?

In the old world, asymmetry of information and hence control of that information was much more prevalent.  In the new world, the internet provides a much faster and more transparent data set for those enlightened enough to recognise the changing order.  CI professionals who can find and utilise this data, essentially re-create a more balanced world since everyone has access to Google and a huge wealth of information accessible in the public domain, including sources such as Twitter.  Out of chaos comes new patterns.

Meanwhile, how does playmaking fit into all this?  I recalled my time as a marketer for a pharma company.  Often, we would analyse the competition and figure out ways to use market research to subtlely try and influence how doctors either perceived competitors on the market or those coming along in the pipeline behind us, then monitor and measure the effects of a particular campaign.  This all takes considerable time and money though.  Yesterday, a member of the audience from Play2run was sharing how his company uses creative models to help companies develop and gain a competitive edge.

"You run plays. Plays are run on you. Every organization and every person runs plays to increase their relative competitive advantage in busy marketplaces. Some do it well. Some try to avoid it. Some do it directly. Some use surrogates. Some run one play at a time. Some run many simultaneously. Almost all do so on instinct but fewer with the support of stated objectives, policies and augmenting research."

Plays2run

You can see more about the system and how it works on the website but the digital world has allowed playmaking and marketing strategies to evolve in a much more sophisticated way than we used to accomplish.  Whether it works effectively or not, I couldn't say, but it's a fascinating area to watch and potentially get involved in.

Overall, it was a very enjoyable and thought-provoking workshop, kudos to August, Eric and Suki for making it a worthwhile 450 mile round day trip!

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Medicare and use of unapproved cancer drugs

Image via WikipediaThere was an interesting article in the excellent WSJ Health blog earlier today exploring when Medicare should pay for off-label cancer drugs. 

Traditionally, Medicare has allowed use of FDA approved drugs with unapproved uses from the American Hospital Formulary System (AHFS).  It is a drug information service that essentially provides Compendia listing for drugs based on a minimum of 2 peer reviewed journal articles with published clinical trial data. 

What are the benefits of Compendia listing? 

Well, for cancer patients with advanced stage disease there are often few therapies available after several lines of treatment have been explored and in many cases, radiotherapy or chemotherapy may not be effective, so use of off-label drugs offers a chance of hope that something new that is being tested in clinical trials may help them.

For pharmaceutical companies, thre are also benefits since Medicare will pay for the therapy and thus the patients are not subjected to the vagaries of compassionate use and all the bureaucracy that goes with it.  This is frustrating for all concerned - insurers, patients, doctors and pharma companies.

In other words, Compendia listing, offers a fair and equitable solution all around that is evidence based.  Usually, the pharma company is completing the larger phase III trials and Compendia listing is based on limited phase II data. Pharma companies should not be forced into a situation where they have to play 'God' either through granting compassionate use or a lottery system.  Far better to allow the patients and doctors to decide what is the best option, providing insurance coverage is viable.

My own experience with this process was based on the listing for Gleevec, a targeted therapy that was approved for CML, a form of leukemia, and was undergoing trials for gastro-intestinal stromal tumours (GIST).  By obtaining Compendia listing via publications from a reputable medical journal such as the New England Journal of Medicine, patients not included in the clinical trials were still able to gain access to the therapy for a condition that was unresponsive to chemotherapy.  The drug was subsequently approved by the FDA for GIST, but a short term solution via Compendia listing was a win-win for all concerned. 

Overall, the system has worked very well so far, but as the WSJ pointed out, expanding the rules to include other compendiums, including that of some physician networks, starts to raise issues of conflict of interest. That's not a good place to go and one wonders why change a workable system? 

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On politics, stem cells and Geron Corp

Image via Wikipedia

The outgoing Bush Government was a well known opponent of stem cell research, while the incoming Obama Administration was publicly supportive of such research.  It therefore came as no surprise last week when the FDA suddenly allowed clearance of the first human clinical trial using embryonic stem cell therapy in patients with acute spinal cord injury.

On Friday, the CEO of Geron Corp, Dr Tom Okarma, was interviewed live on CNBC and had this to say:

"There's no question that the Bush administration was very instrumental in slowing down the progress in a number of ways. But we have really no direct evidence that that actually influenced the FDA's review. So, we really have no view that there was a political overhang at the FDA."

You can find out more from the company press release and the online recording of the webcast.

Geron's website explains their approach with stem cells quite succinctly:

"Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure and diabetes. The company is advancing an anti-cancer drug and a cancer vaccine that target the enzyme telomerase through multiple clinical trials. Geron is also the world leader in the development of human embryonic stem (hESC) cell-based therapeutics. The company has received FDA clearance to begin the world's first human clinical trial of a hESC-based therapy: GRNOPC1 for acute spinal cord injury."

The whole stem cell field is based on a entirely different approach from patients popping a pill or being given an injection or infusion of a drug therapeutic.  Instead, the restoration of organ function achieved by the injection of healthy, functional replacement cells manufactured from human embryonic stem cells.  Embryonic stem cells are pluripotent, which means they can turn into any type of cell in the body and can self renew indefinitely in the undifferentiated state due to high levels of telomerase.

So how does the treatment work?  In the WSJ Health Blog, they summarised it as thus:

"The therapy is designed to generate new myelin, the protective sheath that covers nerve cells and is often severely damaged in spinal cord injuries. A previous study found that paralyzed rats who received the treatment within days of injury generated new myellin (sic) and improved their ability to walk more than rats treated with a placebo."

It should be noted that the clinical trial is a very early phase I study and there are no guarantees that the concept with translate from animals to humans.  In this trial, researchers will inject a stem cell-based therapy directly into the spinal cords of patients who have recently suffered severe spinal injuries. 

Overall, it's an interesting concept and thus we wait with baited breath for a while to see how the results will pan out.

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Work on stuff that matters: is Wy-Pfi a fail?

Earlier this month I came across a thoughtful blog post from Tim O'Reilly entitled "Work on stuff that matters: first principles" and it has been making me think ever since.  Image by

Tim O’Reilly / Flickr

via CrunchBaseO'Reilly outlined three important things and I highly recommend reading his post:

1) Work on something that matters to you more than money.
2) Create more value than you capture.
3) Take the long view.


If we apply those simple parameters to the Wy-Pfi merger announced this morning, I'm left with a big feeling of FAIL on all three, it's like the city public internet router going down and hearing the wails of a thousand lost souls.

Money? It's all about near term sales and revenues, baby!

Value?  For Pfizer shareholders, perhaps, but not for Wyeth employees or society in general.

Long view? Umm, tricky one if the pipeline fails and does not deliver.  What then when Lipitor, Effexor and other drugs go off patent between 2011-2015?  What about the societal impact of baby boomers aging, as Eric Garner pointed out while commenting on the previous blog post?

The thing about this deal though, is that the merger will need Government approval and who knows how they will view this in the current economic climate.  They aren't always a given.

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Pfizer and Wyeth merger - what's next for Pharma and Biotech?

The news wires, Twitter and emails were all a-flutter this morning with the big announcement that Pfizer are buying Wyeth after agreeing a deal yesterday.  The announcement in the WSJ this morning summarises the position admirably when they quoted Tim Anderson of Sanford Bernstein:

“While a WYE acquisition would help sooth the painful period that lay ahead of the company, it will only be a partial salve.”

The NYT got a little excited and opined on the mega deal

"would not only create a pharmaceutical behemoth but would be a rarity in the current financial tumult: a big acquisition that is not a desperate merger of two banks orchestrated by the government."

'Pharmaceutical behemoth?' It's interesting that the companies and the analysts are talking up the deal and yet for many of us in the industry, Wyeth was not considered a big pharma or biotech company, but very much a niche player slow to develop new therapies and often marginal ones in specialist areas such as oncology, viz Mylotarg for AML and a new drug in research, bosutinib for Gleevec failures due to the T315i mutation in CML, where there are very few failures in reality.

Image via Wikipedia

Let's look at what Wyeth actually have:

- A thriving consumer division
- A portfolio of vaccines (useful to Pfizer for their primary care division)
- HRT/women's health products with problems (do they cause breast cancer with long term use?)
- A weak oncology franchise of marginal products soon to be overtaken by other competitors with better efficacy data
- An interesting pipeline full of CNS products for Alzheimers, but question marks over whether any will be effective

Let's look at the hard numbers.  How many blockbusters do Wyeth currently have? None bring in over a billion dollars globally at present. 

The single biggest gain for Pfizer is the addition of the vaccines to their portfolio, which was considered a glaring gap.

What's next?

- Probably layoffs for Wyeth and an exodus much like we saw at Pharmacia when few people wanted to stay with Pfizer.
- Inertia and introversion - mergers are always disruptive to work, quality of life and productivity.

Overall, it's hard to see how this deal benefits Wyeth other than a few golden parachutes for senior management and the Board members. For Wyeth employees they may gain very little other than increased uncertainty and anxiety.  Pfizer gain a few cash cows in primary care, some useful vaccines (eg Prevnar), intravenous anti-biotics (Zosyn) and an undeveloped pipeline that may bear some fruit in the long, rather than short, run.

For the future? 

The biggest problem plaguing the pharma and biotech industry is a chronic lack of new innovation and promising pipelines to replace old products and blockbusters going off patent.  More major mergers and consolidation isn't always a good thing as it stifles creativity and innovation. 

Meanwhile, Congress is looking to curb DTC advertising, which will hurt primary care products more than specialty ones.  Lipitor goes off patent in 2011, so by 2015 the sales revenues will be lagging unless Pfizer can find some replacements to fill the void but Wyeth's future doesn't appear to be much brighter.  Its two biggest drugs, Effexor for depression and Protonix for heartburn, are scheduled to lose patent protection in 2010 and 2011 respectively. 

My overall take is that while the Wyeth products will fill a few short term gaps and sales revenues, in the long run Pfizer will not be much better off, unless one of the Alzheimers drugs in development hits pay dirt, but that's a high risk strategy indeed.

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Quote of the Day - an inspiring thought

"People are like stained-glass windows.  They sparkle and shine when the sun is out, but when the darkness sets in, their true beauty is revealed only if there is a light from within."

Elizabeth Kubler Ross

Image via Wikipedia

Using Delicious to mine for pharmaceutical marketing and competitive intelligence information

One of the challenges facing Pharma product managers and marketers today is the huge overwhelming wealth of data that is available online.  It can be overwhelming and even if you do a Google search for something very specific you may need to wade through many pages of irrelevant information before finding out what you need, if you can even find the needle in the haystack.  The information isn't sorted in any useful format for analysis or comparisons.

Image via WikipediaOne very useful tool is to use bookmarking services to see general trends.  I like Delicious for this purpose because it's easy to use and has Firefox add-ins that allow you to bookmark or clip articles with a bookmarklet from the browser window in either Windows or a Mac.

Recently, I was interested in general trends relating to several pharma companies.  Let's take a quick look at 4 of them, Novartis, Pfizer, Genentech and Amgen.  Once signed into Delicious, I can search for information where people have tagged the companies, drugs, pathways etc.

Here's the basic search for Novartis.  You can see my bookmarks and those of others as well:

As expected you find stuff on drug development, the Novartis Institute and Foundation, clinical trials, job searches and careers information etc.  The tags reflect that too, all benign stuff but interesting none the less.

When looking at Pfizer, however, we get a completely different story!  Nothing on jobs and careers but plenty on Nigerians suing the company after some drug development went wrong and Viagra spam from zombie company computers.  On the positive side, we see some mentions about Web2.0 and Enterprise 2.0 so we might reasonably conclude that Pfizer is looking to be more active in the social media space than the cautious Swiss.  Novartis do at least have a Twitter account, as do other forward thinkig companies such as Boehringer Ingelheim. 

On the Biotechnology side, we also see an interesting trend.  Company news dominates, but there is also information on cloud computing and online grants applications.  The rounded profile suggests the company is active in research and little negative news is topical here. 

Amgen, on the other hand, has a fair amount of negativity to contend with - an embattled CEO, an ongoing fight with J&J over EPO, competition from other companies etc.  On the plus side, there is the cycling tour of California sponsorship except that cynics might wonder why the manufacturer of EPO is sponsoring a cycling race!

If you wanted to be more granular, you can track the individual tags for each company, total them up and compare/contrast them in more detail to get a deeper picture.  The topline analysis tells quite an interesting story though.

You can also search Delicious for novel pathways and find out about what research is being bookmarked.  One such example in oncology is to select a kinase, such as PI3 kinase or PLK1 and see what that brings:

 
I found some interesting articles using that search since I was interested in what drugs were being tested against that particular pathway.  A Google search yielded pages of information that was overwhelming but mining Delicious tags found more useful information more quickly.  You might be interested in several pathways and what's trending in each, thus searching bookmarks is a quick and simple way to get started.

You can also search by drug name and compare different drugs in the same category or tumour type, for both number of bookmarks and the types of bookmarks.  Searching for Herceptin, for example, produces an interesting profile with an emphasis on the data:

 

If you wished to, you could do the same thing for a competitor, lapatinib, and search for Her-2 to see what other compounds are being tested, ie their competitors... so you get the general drift. 

You can use bookmarking services such as Delicious, Mento, Diigo, Connotea, CiteUlike etc to build up a picture of the market you are interested in.  That data can then be tracked and tabulated in a spreadsheet if you need more detailed information.  The bookmarks can also be clicked on, giving you easy access to information shared about the company, drug, tumour type or pathway that you might be interested in. 

Overall, it's a simple and easy way to use web 2.0 and cloud computing tools to perform competitive intelligence gathering from the public domain behind the scenes.

After the Inauguration, time to get back to work

President Obama's speech yesterday at the Inauguration yesterday was a good one for me.  When was the last time you heard an incoming President actually mention science, health and technology?  I posted the full text of the speech on my Tumblog, but here is the except that excited and surprised me:

"We will restore science to its rightful place, and wield technology’s wonders to raise health care’s quality and lower its cost.  We will harness the sun and the winds and the soil to fuel our cars and run our factories.  And we will transform our schools and colleges and universities to meet the demands of a new age.  All this we can do.  And all this we will do."

Now, I'm not sure what science's rightful place is, but at least a President who is not afraid of it and is willing to debate the merits is an excellent start.  With regards to technology in health care, my sense is that it tends to increase costs not lower it, although I'm willing to have an open mind on that.  There was an interesting article in this morning's WSJ Health blog about encouraging e-prescribing amongst physicians for Medicare drugs:

"Medicare this month began paying doctors a bonus if they switch their patients over to e-prescribing. Some private health plans also have begun offering extra payments along with free equipment, such as digital handheld devices. And a coalition of technology companies is giving doctors free software to encourage them to ditch their paper prescription pads. As a result, the number of physicians prescribing medicines electronically has more than doubled in the past year to about 70,000, or about 12% of all office-based doctors."

This is all very interesting and I'm sure it reduces the number of prescribing errors from mis-read or poorly written prescriptions, but whether costs are saved (other than trees) is another matter entirely.

Science and technology can definitely improve healthcare in the form of improved quality of life or longer survival times for cancer patients, for example.  This is usually accompanied by an increase in price and overall costs, just as many other goods and services increase over time.  With the oil crisis forever in people's mnds, science and technology can probably most impact the environment and future energy sources.  Scientific American posted an interesting article on that very topic recently.

Either way, we begin with a bright new day, a new President and hope for the future.  I can't help wondering what a better situation we might have been had Reagan had the foresoght and imagination to spend serious dollars on science and technology for health or energy resources instead of missiles and the Star Wars space screens 20 years ago.  Each new Administration may do their work in the present, but their actions (and lack of them) affect future generations significantly. 

They will ultimately be judged and remembered by their lasting legacy.

9rules... wow, a nice surprise!

After the recent euphoria of making it onto Alltop, this week I found out that the blog has made the latest round of 9rules, an independent website for cool and well written web content. 

I applied last November for the first time and having checked out the Round 7 winners afterwards, I really wasn't expecting to get in and considered it a very long shot indeed especially for a site that is essentially a specialist niche within a niche.  Imagine my surprise when I find out this blog made it onto the list, especially while recovering from flu and a nasty cold!  Hopefully, it will end up in the science section soon.  But, hey I'm certainly looking forward to finding and reading some new blogs for my Google Reader myself.  It's great fun learning from smart people, it's the fastest way I learn new things.

Check out the 9rules link above for yourself and see if any of the blogs listed take your fancy, there certainly were some superb ones in the list.  Mine must have been the ringer ;-), but seriously, it's a great site with some excellent content in all sorts of categories.

Cancer cells - a sense of awe and wonder

One of the amazing things about science and biology is coming across amazing photos and microscopic shots like these, before and after treatment of lung cancer from the Government website Ocean Explorer. 

For a moment I was wondering what on earth human cancer cells were doing on an oceanic site, then I realised that they discuss a collection of sponges and sea fauna, which may contain the active ingredients for the development of various cancer therapies.  The active ingredient is isolated and often re-engineered in the laboratory to create a synthetic version that is more viable for the long term health of the planet.

Here's one example using the red sponge, from which lasonolide was isolated in 1999 and is now in development as a potential anti-cancer cytotoxic agent to induce apoptosis (programmed cell death).  By 2004, five potential lasonolide compounds had been isolated.  Last year, some early preclinical results were published on cell adhesion by the NIH - cancer cells need to adhere to enable the tumour mass to develop via angiogenesis.

Efforts to develop a synthetic version of the molecule are currently underway.  One article I came across referred to the potent anti-neoplastic activity of the compound in pancreatic cells lines, which would be a good tumour type to test it in given the high unmet need and poor survival reported with existing therapies either with single agent gemcitabine or in combination with other chemotherapy agents.

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Lipid technology and cancer therapy for GBM

Continuing the recent theme of new and interesting technologies in cancer therapeutics, today’s blog post looks at neolipid technology and examines how a novel Trojan horse strategy might make existing chemotherapy more efficient and effective.

Tumor cells need to consume large amounts of fat to sustain their rapid growth (angiogenesis).  Neolipid technology takes advantage of this by entrapping anti-cancer agents inside liposomes, which are microscopic membrane-like structures created from lipids (fats).  The tumour then eats the liposome and absorbs the anti-cancer agent at the same time.

One company that is looking at this liposome technology is NeoPharm, a small biotechnology company based in Illinois, who are developing a NeoLipid drug delivery system.  Their lead compound in R&D, cintredekin besudotox, is about to enter phase III trials for glioblastoma multiforme (GBM).  While GBM is one of the most common types of malignant brain cancers, it is also one of the most aggressive.  It typically spreads and grows tentacle-like within normal brain tissue, often damaging adjacent tissues as it grows uncontrollably.  The NCI described the agent thus:

"... composed of interleukin-13 (IL13), a pleiotropic immunoregulatory cytokine, linked to a mutated form of pseudomonas exotoxin A; this agent targets and kills tumor cells that express the IL13 receptor (IL13R). The IL13 moiety attaches to the IL13R on the tumor cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis."

Over the last 20 years there has been very little improvement in treatment success in GBM and patients often survive only a year or so, despite aggressive surgery, radiation and chemotherapy.  The biggest barrier to treatment is targeting the cancer cells without damaging the normal healthy brain cells.  GBM is also more resistant to treatment than most cancers because few drugs are able to successfully cross the blood-brain barrier. 

How is NeoPharm’s compound cintredekin besudotox different from others that have failed in R&D?  Firstly, it is delivered by micro-infusion into the brain rather than via traditional intravenous infusion, which limits its toxicities elsewhere in the body.  Secondly, it is hoped that the liposomes will be absorbed by the fat hungry tumour, thereby enabling more chemotherapy to reach the intended target where it is most needed.  Thirdly, it targets IL13, which is found on the surface of some cancers.  It will be interesting to see if inhibiting IL13 is critical to the survival of the brain tumour.

This combination of regional and molecular targeting is both novel and fascinating; the results for the ongoing phase III trial will determine whether the scientific approach is a valid one or not.

A genetic cause for neutropenia associated with cancer chemotherapy?

A fascinating article in the New England Journal of Medicine caught my eye this morning basically saying that a genetic cause has been found for severe congenital neutropenia. The German study found that severe congenital neutropenia can arise from mutations in the gene for glucose-6-phosphatase. Studies in five patients from two interrelated families of Middle Eastern descent revealed that all were heterozygous for the same mutation in the gene.

The researchers then looked for it in 104 other patients with severe congenital neutropenia with previously unknown genetic origins. Seven of those patients had distinct mutations affecting both alleles. Several different mutations were found.  None of the patients had mutations in other genes known to cause severe congenital neutropenia. The condition is seen in about one in 200,000 births and involves the lack of functioning neutrophils. 

Depending on the gene responsible, other abnormalities may be present as well, including neurological and cardiovascular defects.  In some cases, only neutrophil development is affected.  The gene encodes part of the catalytic region of the glucose-6-phosphatase enzyme, which is involved in multiple glucose metabolism pathways.

Why does this matter?

Well, one of the complications associated with some chemotherapy regimens or drugs is severe neutropenia where the white blood cell count drops drastically below normal and weakens the patient's ability to recover from the treatment because they cannot fight infections. Standard treatment for cancer related symptoms is often to use a growth stimulating factor called G-CSF such as Neulasta (Amgen). Other conditions may also cause a low white blood count such as Lupus, Malaria, Hepatitis viruses, Rheumatoid Arthritis, Aplastic Anemia, Myelodysplastic Syndromes, Parvovirus and others.

Altogether, defects in six separate genes with a variety of functions, are now known to cause neutropenia and explains why some patients suffer from it and others do not.  In addition to the glucose metabolism enzyme encoded by G6PC3, the other mutations are related to mitochondrial function, cytoskeleton integrity, and G-CSF signaling.  One gene encodes a transcription factor of uncertain function, and still another is for the multifunctional neutrophil elastase enzyme. 

What does this all mean?

Well, if you have a condition which is known to sometimes cause low counts and you have the genetic defect, then those patients would most likely benefit from upfront G-CSF treatment to protect against the potential count drop.  This would ensure the patient has a better chance of doing well and also target the costly medication where it is most likely to be needed. 

That's a win-win solution for everyone.

Time is the most priceless commodity we have, especially for cancer patients

Today's Thought for the Day comes in the form of a story a friend shared with me.  It made me think about my own family and the many friends who are going through cancer treatment right now.  Sometimes we need to stop and smell the roses and think about what is really important to us.

A man came home from work late, tired and irritated, to find his 5-year old son waiting for him at the door. 

SON: 'Daddy, may I ask you a question?' 

DAD: 'Yeah sure, what it is?' replied the man. 

SON: 'Daddy, how much do you make an hour?' 

DAD: 'That's none of your business. Why do you ask such a thing?' the man said angrily. 

SON: 'I just want to know. Please tell me, how much do you make an hour?' 

DAD: 'If you must know, I make $50 an hour.' 

SON: 'Oh,' the little boy replied, with his head down. 

SON: 'Daddy, may I please borrow $25?' 

The father was furious, 'If the only reason you asked that is so you can borrow some money to buy a silly toy or some other nonsense, then you march yourself straight to your room and go to bed. Think about why you are being so selfish. I don't work hard everyday for such childish frivolities.' 

The little boy quietly went to his room and shut the door. 

The man sat down and started to get even angrier about the little boy's questions. How dare he ask such questions only to get some money? 

After about an hour or so, the man had calmed down , and started to think: 

Maybe there was something he really needed to buy with that $25.00 and he really didn't ask for money very often. The man went to the door of the little boy's room and opened the door. 

'Are you asleep, son?' He asked. 

'No daddy, I'm awake,' replied the boy. 

'I've been thinking, maybe I was too hard on you earlier' said the man. 'It's been a long day and I took out my aggravation on you. Here's the $25 you asked for.'

The little boy sat straight up, smiling. 'Oh, thank you daddy!' he yelled. Then, reaching under his pillow he pulled out some crumpled up bills. 

The man saw that the boy already had money, started to get angry again. 

The little boy slowly counted out his money, and then looked up at his father. 

'Why do you want more money if you already have some?' the father grumbled. 

'Because I didn't have enough, but now I do,' the little boy replied. 

'Daddy, I have $50 now. Can I buy an hour of your time? Please come home early tomorrow. I would like to have dinner with you.' 

The father was crushed. He put his arms around his little son, and he begged for his forgiveness. 

It's just a short reminder to all of you working so hard in life. We should not let time slip through our fingers without having spent some time with those who really matter to us, those close to our hearts. Do remember to share that $50 worth of your time with someone you love. 

If we die tomorrow, the company that we are working for could easily replace us in a matter of hours. But the family & friends we leave behind will feel the loss for the rest of their lives.

Thanks to Nigel Grainger of Fleet Risk Consultants for sharing the story.

With regards to a cancer patient's real life story, you can't get any better than the delightful Alicia Staley (@Stales) who shared this great post on her experiences - read it, it will make you stop and think a bit - LINK.  I am truly humbled to be her online Twitter buddy and follow her story of courage and determination.  Alicia, you ROCK!

Quote of the Day

"Thinking is the hardest work there is. Which is probably the reason why so few men engage in it."

Henry Ford