Closing one big door, as many more swing open!

Few landmark institutions in Montreal have made as characteristic an imprint on the city's collective zeitgeist as the legendary Royal Victoria Hospital on Pine Avenue, which is finally closing down completely this afternoon. In what is the largest hospital relocation in Canadian history, today saw the transportation of some 154 patients (most estimates were considerably bigger - between 220 and 250) from the RVH down to the new MUHC Glen site. 

I live extremely close to the old hospital so couldn't resist popping up to grab a little slice of history on what turned out to be a lovely, sunny, spring Sunday morning. The first thing that I noticed was how little fuss being made, with no sign of police or traffic control anywhere, and ambulances slipping seamlessly and quietly in and out of the RVH driveway with apparent military precision and ease. It was actually more tranquil than a typical day, which is something I imagine that was intentional and benefited the patients greatly.

Many reports had the move slated for something like 7am until 3pm (or later if need be) but in fact, so smooth was the procession of ambulances up and down Atwater to-and-from the RVH that the last and 154th patient arrived safely at MUHC by around 12:30PM, which underlines what was an incredibly organised process for what could have been a logistical nightmare! That is probably down to the chosen partner for this move, which was Health Care Relocations from Peterborough - an outfit renowned for transfer of hospitals from one site to another. Kudos to them and Team MUHC for what was an undoubted success. 

 

On the picture at left above is patient #58 (there were already an impressive 57 patients safely arrived at the Glen site by 9:30am!) departing the RVH for their own very personal voyage and introduction to the new superhospital, while at right is the fleet of ambulances returning to RVH for their next pick-up. The pictures truly do tell the story of what was a very calm scene and if you didn't know better, you could have been forgiven for simply thinking that it was just a normal quiet Sunday morning at the hospital!

There was news from MUHC at the Glen site that became a perfect kickstart to the day just before the move commenced, and that was the birth at 6:55am of the very first baby born at the new site - a healthy 7.9lb boy. That may well turn out to be quite an historic birth, even if it might take a decade or two for it to sink in as far as he is concerned, but I wouldn't be surprised if he gets a ward named after him some day!

There were 2,500 hospital staff and volunteers, various medic vehicles, and a fleet of 32 ambulances that were involved in the move, and there are already celebrations going on after a glitch-free operation and smiles from patients arriving to what appeared to be "like hotel rooms" in comparison to their previous premises up the hill. Even as healthy adults, moving home is considered to be one of the most stressful events in our life, and I can only imagine what that means and feels like when it necessitates being moved from your hospital bed into totally unfamiliar surroundings. 

 

As happy a day as it no doubt is, I am a huge fan of big old buildings like the RVH, and seeing it cleared out and closed down on a sunny Sunday after some 122 years in residence, perched on high above the cityscape, well, it was also a day tinged with nostalgia, memories and some pathos. Who knows how many lives passed through those doors, lives changed forever by illness and disease, many never exiting again, as well as the extended families who were transformed by events that transpired there. Over a century of medical and individual history swirling inside the corridors behind that greystone, as the big door gets closed and sealed for the very last time.

But you know, as one big door gets closed, so do many others swing open, which is exactly what happened at the new MUHC today, and collectively they represent one massive door opening on improved contemporary healthcare for Montrealers, for hopefully many generations to come. I just hope that as chic and modern as the new MUHC undoubtedly is, that the authorities demonstrate a desire to preserve the old hospital facade as a permanent reminder of its existence and service to the community, and don't permit its demolition and conversion into the pervasive and even seemingly inevitable installation of condominiums. 

But that's a question and a problem for another day, and right now it's best to just marvel at our new superhospital and the settling in of those 154 former RVH patients as brand new MUHC-RVH patients! I had the privilege of visiting the unopened hospital last December (as reported in an earlier post on this blog) and it's clear that they are going to be exceptionally comfortable and well taken care of there. On that note, I shall leave you with a photograph of that last patient arriving at the Glen site shortly after noon today. Bravo to all @MUHC!

Taking the high road when it comes to epilepsy?!

Medical marijuana continues to make the news these days, and not just over the ethical and legal issues involved in destigmatising and legalising of this heretofore illicit substance; this week the news was abuzz about its potential use as a new candidate therapeutic for severe epilepsy. There have been other proposed benefits in adults of the plant-derived substance that maybe seemed more obvious (pain, for example) but it is very intriguing that researchers may have stumbled upon something that will benefit children in particular. 

The UK's GW Pharmaceuticals has been a proponent of the more pharmaceutically-minded sector of the medical marijuana movement for the past several years, and has hinted at promise for the green stuff in the treatment of severe, treatment-resistant epilepsy. This is an extremely debilitating condition and regulatory authorities have granted GW entry to an expanded access program which allows such patients to receive unapproved products in the face of little other option or hope. 

What got the attention of the big news networks this week was the announcement by GW at the American Academy of Neurology that their experimental drug Epidiolex reduced seizure rates by as much as 50% (or more) in an open-label study. Now, no one wants to overreach on this and claim that the data obtained replaces the need for a full placebo-controlled clinical trial, but the idea was to get an early read on things and generate some excitement on GW's aligned Phase III trial for the drug candidate.  

Notwithstanding the use of the word "high" in the title above, the active ingredient in GW's treatment is cannabidiol, a component of marijuana that is not involved in inducing the high associated with the plant's use. This aspect should help to somewhat legitimise the use of the drug (because we can't have terminally sick people experiencing a high, can we?!) and even separate it from the term "medical marijuana" given that no smoking is involved - which is a very good thing given that children are going to be primary recipients of the therapy. 

GW has developed an oral droplet form of the cannabis-derived molecule which does retain the beneficial medical effects of the compound, including its recognised anti-seizure and anti-inflammatory properties. Like marijuana itself, the legality of cannabidiol is somewhat hazy (you have to peer through the smoke!) in that it varies from territory to territory. But in many cases (including in the USA), cannabidiol remains classified as a Schedule I controlled substance, making even possession of it illegal.

The clinical study being run by NYU's Dr. Orrin Devinsky has achieved a remarkable 54% reduction of seizures observed in 137 patients who were on the therapy for 12 weeks, including reaching similar numbers in those afflicted with either Dravet or Lennox-Gastaut syndrome. GW has or is preparing to enrol patients in Phase III trials in the latter two categories (electrically distinct forms of seizures) this year, and such data are extremely encouraging, especially as Epidiolex will be given fast track review by the FDA as an orphan-designated drug candidate. 

As esoteric as the venture may seem alongside more classical pharma medicines, GW is building a solid development pipeline from its cannabinoid platform, and there are ongoing trials in cancer pain, diabetes, ulceritive colitis, schizophrenia and epilepsy. If they are on the right track, as they appear to be based on some of the recent data shared with the media, then they could be in for a very substantial payday via their relatively diverse pipeline. They previously partnered their oral cabbaninoid Sativex (for multiple sclerosis) with Bayer, have also partnered it for cancer pain, and this drug has since been launched in 15 countries with regulatory approval in another dozen - so they are going places. 

GW's cause is garnering attention from various epilepsy advocate organizations such as the Epilepsy Foundation in the USA, who are lobbying federal agencies to build on the promise achieved to date by loosening regulations and increasing access to cannabis-derived medication when it is warranted. Their current mandate includes - 

• Calling on the Drug Enforcement Administration to implement a lesser schedule for marijuana so that it can be more easily accessible for medical research
• Supporting appropriate changes to state laws to increase access to medical marijuana as a treatment option for epilepsy, including pediatric use as supported by a treating physician
• Supporting the inclusion of epilepsy as a condition that uses medical marijuana as a treatment option where it is currently available
• Supporting research on multiple forms of cannabis and seizures

There is definitely some movement in the right direction for advocates, patients and drug developers alike, and if GW can achieve the data hoped for in their placebo-controlled Phase III trials then they may well be riding high while keeping seizures in epileptics low. Their current high of $114 on Nasdaq is surely a reflection of that optimism and the future for all concerned might be looking very green indeed when the smoke begins to clear!

A long time coming - the BAPtism of Alzheimer's disease!

The prevalence of true "age-dependent" diseases is on the rise, due in large part to game-changing successes in modern medicine whereby previous major killers such as heart disease and certain cancers are largely survivable, today. A major outcome of such success is that we are an increasingly aging population, and inevitably, the reduction in deaths due to maladies generally associated with middle age means that we are experiencing an avalanche in the occurrence of those directly related to old age. 

We are of course talking about CNS diseases, and hardly a week goes by in the news media without hearing something about cognitive decline, dementia, Alzheimer's disease or Parkinson's disease. Alzheimer's disease in particular is a very feared diagnosis which has been "spreading" explosively in the aging population - it is estimated that some 15 million people globally are afflicted - with that number predicted to rise to a massive 75 million by 2030. Houston, we have a problem!

Notwithstanding the amount of research that has gone into better understanding this devastating condition, one of the confounding aspects of developing better drugs (or in this case, any drugs that work) for Alzheimer's disease is defining a unifying mechanism underlying it's onset and progression. While we have heard much bout beta-amyloid plaques in the brains of patients suffering from the disease, as a causative phenomenon, to date any clinical trials targeting such plaques have been disappointing to say the least. 

The non-baptists (beta-amyloid peptide) certainly got more attention due to the lack of any convincing proof that amyloid plaques cause the disease, but their favourite target, tau, and hyperphosphorylated tau-containing neurofibrillary tangles, has been equally problematic. Tau was eventually shown to be downstream of amyloid plaque and in fact it has been suggested that tau (and even plaque) may be a protective mechanism arising due to the brain injury underlying the disease.

After years of hearing nothing but depressing news on the subject, it was rather shocking recently to actually hear something very positive-sounding indeed, from none other than Biogen Idec. While I think we all believe that it is too much of a medical challenge to successfully treat patients in later stages of this brain-destroying disease, the hope remains that with better and earlier diagnosis, we can get to patients earlier and slow or prevent the progression of the disease, in a disease-modifying fashion - that is the holy grail for an Alzheimer's therapeutic. 

Thus the announcement from Biogen that they had slowed cognitive decline in a small study of early or mild cases of Alzheimer's disease was striking - apparently in a small group of less than 200 people, Biogen's aducumab not only significantly slowed cognitive decline (a read-out directly associated with the disease) but did so in correlation with reduction in the levels of plaque in their brains! This is tremendously exciting not only because the end result is precisely what physicians and drugmakers have been desperately asking and searching for, but also because it may have finally underlined the causative role of brain plaque in the disease. 

If brain degeneration is the result of plaque buildup and we can loosen and remove that plaque, then we can slow the degeneration and treat the disease. Although other major players such as Pfizer and Eli Lilly (among other) have failed to achieve this small but hugely significant success, Biogen may have gotten ahead by very carefully confirming the actual presence of the disease, and eliminating patients suffering from other forms of dementia who previously would have been diagnosed with Alzheimer's and included in clinical trial groups. Study design may be the key factor that has allowed Biogen to separate themselves from the pack. 

On the back of this extremely hopeful news, another much smaller outfit saw enormous advantage for them and weren't shy about saying it. Martin Tolar, formerly head of Pfizer's Alzheimer's disease group and current CEO of Framingham-based Alzheon, is using the Biogen data as formal proof of the amyloid hypothesis, while provocatively claiming that Alzheon is way ahead of even Biogen. 

The reason? Well, Alzheon not only have an oral plaque-busting pill, as opposed to Biogen's injected biologic, but further, Alzheon are working on a molecule which has seen some very serious Phase III testing by a Canadian company, no less. The drug, tramiprosate, was yet another candidate that got buried in the Phasee III graveyard of Alzheimer's clinical trials, but Tolar points out that he knows what was wrong with it and the reformulated version of it is the real deal - he also has a dataset more than 10-fold larger than Biogen's that he can draw on, thanks to the trials sponsored by Neurochem (now Bellus Health) of Montreal. 

There is a lot at stake here, and not only for the healthcare system which could be bankrupted in decades by caring for patients in the absence of any disease-modifying treatment.  The fact that Biogen's market cap jumped by a massive $10B in one recent day and has increased 5-fold in five years emphasizes the aniticipated income if they get there in the end - that fiscal excitement arose in large part via the confidence evident in their move to bypass Phase II trials completely and to enter Phase III trials later this year. 

It's estimated that Biogen should get to market by 2020, but Alzheon say they can get there by 2018 given that their molecule has already been in Phase III and is considered extremely safe for human use. Two years earlier is huge in the Alzheimer's market, and will not only rake in billions of dollars, but if Alzheon's pill works then it could have a serious impact on market entry of Biogen's biologic. 

Unquestionably, if Alzheon can get to market, it will serve as a form of vindication for the discoverers of the drug here in Montreal, but it would be somewhat of a bitter pill to swallow at the same time. The benefit to mankind would be huge, and that's a massive payoff in an of itself, but I dare say the original investors in Neurochem/Bellus would turn in their graves in the Azlheimer's clinical trial cemetry, at the mere thought of others making billions annually from a discovery they funded. Such is life in the high stakes high risk venture of drug development in the CNS segment - the few, the proud, the brave!

[Shortly after the news from Biogen, the Mayo clinic came out with new data from the tauist side of the pews, claiming that it is tau that is most clearly associated with cognitive decline and memory loss, and it drives disease progression, not amyloid - from a study of over 3,000 post-mortem brains. It looks like the baptist versus tauist argument rages on!]

Nanoparticles - tiny tools with huge potential!

When the sequencing of the human genome was completed over a decade ago, there was enormous hope that the equally enormous potential encoded in those 3 billion base pairs of DNA would unlock the mystery of human disease if not of our very existence itself. However, I don't think it's too much of an exaggeration to say that the code from which we derive remains pretty much that - a code - and that there is much that still needs decrypting regarding tthe double helix and this mortal coil. 

One area where we have made significant progress thanks to genome sequencing is in medical diagnostics and predicting the likelihood of not only succumbing to a particular disease but also of how a patient may respond to standard-of-care treatment. As the public becomes more and more educated about the value of the information intertwined in their double helix, personalized medicine became the goal and the race was on to get to the magical "thousand dollar genome", thereby making it much more of a test reachable for "everyone".

We are currently in the era of thousand dollar genome sequencing and personalized medicine is becoming more of an everyday term, but to routinely use DNA sequence analysis as a tool in contemporary medicine there remains a need for faster, cheaper high throughput DNA sequencing. A new development referred to as "atomic chicken wire" may represent the future in this area, with one atom layers of hexagonally arranged carbon (graphene) being the key - the authors of a recent paper in Nature reporting that graphene can measurably detect adenine, guanine, cytosine and thymine - the four nucleobases making up our DNA. 

The ability of each base to impact the electronic structure of the graphene sheet allows that impact to be measured electrically, potentially permitting major improvements in speed, throughput and accuracy of DNA sequencing. The idea is that a single DNA molecule passes through a nanopore in the graphene sheet "like a string of beads passing through chicken wire" and the graphene sensor reads the sequence in high throughput fashion in real time. It's a potentially explosive technology and one can imagine bulk graphene sensors simultaneously reading multiple molecules of DNA with individual costs being reduced dramatically. 

Another diagnostic area where nanoparticles are making a big splash is prostate cancer. Never mind the thousand dollar genome, researchers at the University of Central Florida (UCF) have developed a $1 blood test using gold nanoparticles that outperforms the current PSA screen for prostate cancer. This is eztremely exciting given that the earlier we detect basically any cancer, the better the chance that we can resolve it before it becomes unmanageable.

The simple test developed by UCF scientist Qun Huo makes significantly earlier detection possible, and that's massive for one of the deadliest cancers in men. Huo's test takes advantage of the unique ability of gold particles to absorb and scatter light, and is focused on the body's immune response to cancer whereby certain biomarkers (antibodies) that are upregulated adhere to the gold nanoparticle surface, changing their size and light scattering properties. 

Huo's team at UCF's NanoScience Technology Center developed a technique known as nanoparticle-enabled dynamic light scattering assay (NanoDLSay) to measure the size of the particles by analyzing the light they scatter - that size reveals whether a patient has prostate cancer and additionally indicates how advanced it may be. Although we normally associate gold with great expense, in this case the nanopartciles mean a nanocost and this could make such a test totally routine from a finger prick of blood in the doctor's office. 

Prostate cancer is the #2 cause of deaths due to cancer in men, with close to a quarter of a million new diagnoses and 28,000 deaths each year. To date, the PSA test is the most routine screening tool available, but it produces many false positive results -- resulting in painful biopsies and elaborate treatments -- and detractors have likened it to nothing more than a coin toss in terms of reliability. The need is real and Huo's test could be a total game changer in men's health and medical treatment.

Pilot studies on Huo's test have shown that it determines with 90-95% confidence that the result is not a false positive, while in terms of false negatives, the test is less reliable (50% confidence); however this is still significantly higher than the PSA test's 20% confidence in false negatives, and Huo is working to improve this number. The data from this pilot study were published recently in ACS Applied Materials & Interfaces and Huo is also scheduled to present her findings in June at the TechConnect World Innovation Summit & Expo in Washington, D.C.

She hopes to complete major clinical trials quickly and get the test in doctor's hands in two or three years, while also researching how the technique could be used for various other cancers, stating that she could be onto a "potentially universal screening test for cancer". On the back of her discoveries, Huo has co-founded Nano Discovery Inc., a UCF startup which will commercialize the new diagnostic test once it obtains marketing approval. 

This cheap test using nanoparticular gold could be worth way more than its weight in gold, and the only aspect of it that will remain "nano" will be the size of the particles themselves! At AmorChem, we have a keen eye on the nanotechnology space and in fact we recently invested in a nanoparticle technology discovered at the University of Waterloo. The field is forging ahead and it's only a matter of time until approaching medicine from the most minute viewpoint will pay off enormously in terms of the bigger picture.