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Dr. Titus’ Insights: Alzheimer’s Research and the Work of Dr. Schubert

This week: MJNA President & CEO, Stuart W. Titus, PhD follows Up on Alzheimer’s research, talking more pharma failures and the profound work of Dr. David Schubert

Next week: Hemp Seed Nutrition

This week, we saw two additional Alzheimer’s studies show more failures in the quest to arrest the decline of mental and cognitive function in our aging population.  Last week, I mentioned in my weekly column Alzheimer’s and its link to the industrial disease of the NFL, CTE.  Further that there is new hope, thanks to the progressive efforts of a Dr. David Schubert of San Diego’s Salk Institute.

Dr. Schubert, pictured below, has spent a good deal of his career as a researcher at the Salk Institute looking into potential approaches to the Alzheimer’s problem in America. Currently, we believe there are 5.4 million Americans diagnosed with Alzheimer’s, and this figure is expected to triple within the next 35 years (Link: http://www.alz.org/facts/).  We spend over $200 billion annually on healthcare for these patients – and if trends continue, it is estimated that by the year 2050, we will be spending over $1 trillion annually.

Dr. David Schubert, Professor and Laboratory Head, Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, San Diego California

Dr. Schubert has described his research career herein:

“I have run a small lab at The Salk Institute for many years.  My undergraduate degree is in chemistry, Ph.D. is in immunology, and my early career was in cell biology and electrophysiology.  I went on to study growth factors, which led to work based upon protein chemistry and proteomics.  For the past decade the laboratory has been working on cell death pathways associated with glutamate toxicity and AD.  Much of the early work on the basic biology of the amyloid precursor protein and Aβ (amyloid-beta) toxicity was from my laboratory.  This work led to the desire to develop drugs for AD (Alzheimer’s disease / Alzheimer’s Dementia) and related conditions such as Parkinson’s disease.  Therefore, we have developed the expertise to do the necessary medicinal chemistry, assays and pre-clinical laboratory work required for this work and have an excellent publication record in this area.”

Link: https://www.michaeljfox.org/foundation/researchers.php?id=1349

Staying with the positive and the potential for future research, Dr. Schubert’s recent research, as reported by the Salk Institute, can be read here:

https://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

Herein, Dr. Schubert makes the case for cannabinoids to not only assist in the decrease of brain-related inflammation – but to also, simultaneously assist in the removal of beta-amyloid Protein aggregation (plaques), which are a likely cause of Alzheimer’s.  This research is especially astounding, particularly when one looks at a report published by Bloomberg reporters Robert Langreth and Cynthia Koons titled: After 190 Tries, Are We Any Closer to a Cure for Alzheimer’s?

In the Bloomberg report, published June 26, 2016, the reporters summarized the findings of our research community to date: “All told, at least 190 Alzheimer’s drugs have failed in human trials, according to Bernard Munos, a senior fellow at FasterCures, a health non-profit.”

Link:http://www.bloomberg.com/news/articles/2016-06-27/after-190-tries-are-we-any-closer-to-a-cure-for-alzheimer-s

Further, Bloomberg goes on to say:

“Big Pharma may have thrown in the towel if Alzheimer’s weren’t one of the industry’s last big untapped markets.  More than 5 million Americans have the disease, and that number may rise to 13.8 million by 2050, according to the Alzheimer’s Association.  Existing medicines, which mostly treat symptoms, have combined sales of $3 billion today.  ‘If any of these drugs actually manage to slow the progress of the disease, their sales potential would be orders of magnitude higher,’ says San Fazeli, senior pharmaceuticals analyst for Bloomberg Intelligence.”

In the world of Alzheimer’s research, there are two distinct schools of thought.  One seeks to focus on these beta-amyloid plaques as the primary cause of brain dysfunction, and the other school focuses in efforts toward tau protein tangles, which have a similar effect to diminish brain communication activities.  The amyloid camp shows certain genetic evidence “has been so compelling,” according to Roger Perlmutter, head of research at Merck.  In 2012, overseas researchers discovered a rare gene mutation that appears to protect against Alzheimer’s by lowering amyloid production. However, as numerous amyloid drugs have failed in clinical efforts, the industry has refocused toward Tau.  Tau is similar to a beta amyloid type of brain protein aggregation, which is more commonly associated with traumatic brain injury (TBI) or Chronic Traumatic Encephalopathy (CTE, aka the “industrial disease” of the National Football League, NFL).

Interest in Tau protein research gained momentum in 2012 and 2013 as studies showed the toxic protein can spread between brain cells, which makes it an easier pharmaceutical target.  Several pharma companies are working toward this Tau tangle aspect, including TauRx Pharmaceuticals, Johnson & Johnson, and AbbieVie.

In an effort to describe the two worlds of clinical thought regarding Alzheimer’s causation, an excellent quote comes from Samantha Budd Haeberlein, VP of Clinical Development at Biogen (NASDAQ: BIIB), a pharmaceutical development company focusing on two drugs that are nearing human trials.  Ms. Haeberlein mentions that “while tau is ‘possibly the executioner’ of brain cells, amyloid is ‘the gun.’”

Since the June 2016 Bloomberg report, there have been an additional two failures in the world of Alzheimer’s, bringing the Bloomberg total now up to 192.  As reported by Damian Garde in STAT Biotech on July 27, 2016: “A closely watched treatment for Alzheimer’s came up short in a late-stage trial, marking the latest setback in a field wracked by years of failure.”

Link: https://www.statnews.com/2016/07/27/alzheimers-drug-taurx/  

The latest failure, TauRx Pharmaceuticals drug LMTX, was meant to block activity of bodily proteins that many neuroscientists believe contribute to the brain destroying effects of Alzheimer’s.  Although the LMTX treatment is still being researched via a second study involving about 700 people, with additional data expected to be released later in 2016.

Further, the STAT News article about TauRx Pharma mentions that the “results are another blow to Alzheimer’s research.  Academics, startups and pharmaceutical giants have poured decades of work and billions of dollars into finding treatments.  One therapy after another has looked promising in the lab – only to crumble when tested in large patient populations.”  An analysis by the Cleveland Clinic shows that 99.6% of Alzheimer’s patients tested between 2002 and 2012 have failed to show progress in clinical trials.

Alzheimer’s is considered irreversibly fatal according to STAT News.

MedPage Today, during the final week of July 2016, also showed the failure of another recent study involving “intense vascular risk management” to prevent dementia in a large trial conducted in The Netherlands.  There was no significant difference in the proportion of patients who developed dementia over about 6 years – whether they received intensive management or just standard care.

Cardiovascular risk factors are associated with an increased risk of dementia.  3,500 patients aged 70 to 78 were followed for a median of 6.7 years with the primary outcome of the study being the development of dementia.  Unfortunately, the effort, though showing benefit for blood pressure and other health benefits, did nothing for the risk of dementia.

Which is why the work of Dr. Schubert becomes so profound with far-reaching implications.  We look forward to further research and study of cannabinoids as an answer to the Alzheimer’s problem our senior citizens face.

As a review, here is a synopsis of Alzheimer’s:

  • There are billions of nerve cells in the brain called neurons.
  • Neurons transport messages and communication throughout the brain using electrical signals.
  • On the surface of the neuron is a protein called Amyloid Precursor Protein (aka APP).
  • Amyloid Precursor Protein (APP) is pulled from the surface of the neuron by enzymes.
  • This frees up a protein called Beta Amyloid.
  • In a healthy brain, these Beta Amyloid protein fragments are broken down and eliminated.
  • In brains of people with Alzheimer’s disease, these fragments accumulate.
  • These fragments then form sticky, insoluble plaques.
  • These amyloid plaques accumulate outside the neuron.
  • These buildups may block cell-to-cell communication at neuronal junctions, known as synapses.
  • Synapses are tiny gaps between neurons where signals (think spark plugs) jump the gap.
  • Whether beta amyloid plaques cause Alzheimer’s disease remains controversial.

And now a review of the brain’s lymphatic system, called the Glymphatic system:

  • Protein fragments are broken down and/or eliminated via the body’s lymphatic system.
  • The lymphatic system breaks protein down into individual amino acid components.
  • These amino acids can be re-combined by the body’s cells to form new proteins.
  • In the brain, we have a separate lymphatic system known as the Glymphatic system.
  • This was discovered by University of Virginia at Charlottesville researchers in 2015.
  • The Glymphatic system is a waste clearance system.
  • It promotes the elimination of soluble proteins and metabolites from the brain.
  • It promotes similar elimination of protein and metabolites from the Central Nervous System.
  • Besides elimination, the Glymphatic system facilitates distribution of several compounds.
  • This includes distribution of glucose, lipids, amino acids, growth factors and neuro-modulators.
  • This distribution goes to and nourishes all brain and neuronal cells.
  • This system functions mainly during sleep and becomes disengaged during wakefulness.
  • Potential neurotoxic waste products, such as beta amyloid are eliminated by this system.
  • The Glymphatic system can be suppressed with various diseases.
  • The failure of the Glymphatic system might contribute to pathology including: neurodegenerative disorders, traumatic brain injuries, stroke.
  • And potentially Alzheimer’s disease.

Link: https://www.nih.gov/news-events/nih-research-matters/lymphatic-vessels-discovered-central-nervous-system  

A NIH Link to the research finding is found here: http://www.ncbi.nlm.nih.gov/pubmed/25947369

Looking to the future:

Can cannabinoids, by removing both brain inflammation and these beta amyloid plaques, jump-start faulty Glymphatic systems back toward their proper function?  Dr. David Schubert and the Salk Institute are earnestly researching these ideas, and answers for Alzheimer’s, dementia, and traumatic brain injury may be at hand.

I look forward to providing readers additional updates in the near future.

 

To Good Health –

Stu

 

Stuart W Titus, PhD

President & CEO

Medical Marijuana Inc. (OTC: MJNA)

 

  • August 5, 2016
  • Eve Ripley