The National Football League has taken big steps with rule changes, and fine incidence and costs in the last couple years to try and better protect players, especially from head injuries. Citing Football Outsiders as their source, PBS.org reports that there have been 135 concussions in the NFL through week 15 this year, equating to a projection of 153 for the 2013 season. This would be a decrease from 171 in 2012, but up from 129 in 2010, the year the NFL started implementing rule changes.
Safe to say, the results have been mixed. The bottom line is that football is not a contact sport; it is a collision sport and, like it or not, concussions are going to happen. That is, unless defensive players slow to a walk before contact or offensive players simply fall down anytime anyone is in their way.
Not that long ago, the NFL was denying correlations between concussions suffered on the playing field and neurological problems and behavioral changes in players once they retired. That attitude has changed 180 degrees with scientific evidence and the suicides of high-profile NFL alumni, including future Hall of Famer Junior Seau in 2012. Seau, along with other former NFL players, was shown to have chronic traumatic encephalopathy (CTE), a degenerative brain condition tied to repeated head trauma that, unfortunately, can only be diagnosed in an autopsy.
The NFL settled a paramount lawsuit in August involving more than 4,500 former players and their families for $765 million, with a portion of the settlement costs being earmarked for research into the effects and prevention of concussions. The National Institute of Health announced earlier this month that it has selected eight projects designed to understand some fundamentals of traumatic brain injury, with part of the funding coming from a 2012 donation of $30 million made by the NFL.
Understand that this is not an exercise to pat the NFL on the back for putting more money into research after thousands of accusations that the league downplayed the severity of concussions, possibly resulting in countless former players ending up with Alzheimer’s, CTE, dementia, depression and many other diseases or conditions. It is encouraging, though, to see the power of an organization the magnitude of the NFL being used to finally put a brighter light on a problem that is in such dire need of research and new therapeutics. The benefits can extend far beyond the list of the relatively small population that actually make it to the professional level to help military personnel, sports players of all ages and games, accident victims and many, many more.
Researchers at the UCLA recently made what is probably the breakthrough of the year (maybe all time) in CTE, saying that they believe that they may have come up with a diagnostic for the disease. Scientist built upon their studies for Alzheimer’s Disease using a chemical marker called FDDNP and a PET scan to detect for accumulation of tau, a protein that builds-up in the brain of Alzheimer’s Disease patients and, as it happens, CTE patients. Preliminary results from a small patient population of nine former NFL players, including Hall of Famers Tony Dorsett and Joe DeLamielleure, identified tau concentrations, suggesting that the ex-players are at risk to develop CTE. The research is still in its infancy, but as the library of data grows, researchers should be able to identify where tau accumulates, which subsequently can hopefully lead to new therapies to treat.
In the public domain, there are hundreds of biotechnology companies targeting cancer, heart disease and other “popular” diseases, but comparatively few in the neurological space. The reason is pretty simple as there is somewhat limited research underscoring the mechanisms of the conditions, which doesn’t lend to rapid development. Further, the regulatory process can be long and expensive to try and commercialize a product, resulting in the majority of companies opting for alternatives that are less-risky pathways to potential revenue.
Amarantus Biosciences, Inc. ($AMBS)
Amarantus Biosciences is one of the few public companies that has said they are looking at CTE. The Sunnyvale, California-based company is focused on developing treatments and diagnostics for diseases associated with neurodegeneration and apoptosis. Amarantus has completed a Phase I clinical trial of its blood test, called NuroPro, as a diagnostic tool for Parkinson’s disease and two Phase I trials of LymPro as a blood test for Alzheimer’s Disease.
Similar to the methodology behind UCLA’s expansion into CTE from Alzheimer’s, Amarantus believes that the basis of cell-cycle dysfunction that forms the cornerstones of LymPro test for Alzheimer’s can be employed to diagnose CTE. LymPro works by identifying immune-based biomarkers in the blood to differentiate Alzheimer’s patients from those without the debilitating disease and those with other forms of dementia. The technology is still conceptual related to CTE, but could prove very valuable if Amarantus scientists are correct in their contentions, as a blood test would have many advantages over the more extensive procedure at UCLA. Investors will be looking for the company to conduct some proof-of-concept studies to confirm LymPro as a CTE diagnostic.
Neuralstem announced in April that it is working with the NFL Alumni Association to develop a trial for treating ex-NFL players suffering from traumatic brain disorders (TBI). The Rockville, Maryland-based company is developing NSI-189 as the leading small molecule compound in its neurogenic drug platform. Apropos, the company is also conducting some cutting-edge clinical research with NSI-566 for Amyotrophic Lateral Sclerosis, often known as “Lou Gehrig’s Disease.” Neuralstem completed dosing in a Phase 1b trial of NSI-189 to treat major depressive disorder (MDD) during the third quarter. Data from the trial is being compiled, which investors should be looking for in the near term.
This data will also be utilized in design work for a study of TBI. Research has shown the oral drug to stimulate new neuron formation in the hippocampus, a region of the brain that atrophies in depression and could play a role in other conditions, such as those resulting from repeated mild head trauma. The compound has also been shown to increase hippocampal volume, as volume levels are known to be lower in patients suffering from MDD. Groundbreaking research called the Professional Fighters Brain Health Study has determined that the reduction in size of the hippocampus is a prelude to physical symptoms of cognitive changes in boxers. With that in mind, the data from Neuralstem’s Phase 1b trial brings with it many possibilities to expand research into other brain conditions, such as Alzheimer’s disease and Post-Traumatic Stress Disorder.
Exosomes, tiny vesicles excreted by cells into body fluids, are a compelling new area of research that may play a big role in diagnosing and treating neurological conditions (as well as other diseases, such as cancer). For years, scientists thought exosomes to essentially be “garbage cans” for cells, but newer research shows the key role that they play in homeostatic health.
Life Technologies, Inc. ($LIFE)
From a diagnostic perspective, an increase in exosomes can be indicative of a particular condition or disease. In cancer, for example, research shows that tumors release exosomes to trigger the death of cancer fighting immune cells and facilitate metastasis. Life Technologies has stepped up as a clear leader in this field with a litany of tools and technologies to isolate and analyze exosomes and the cargo they are carrying. If investors want a piece of that action, though, they’re going to have to grab shares of Thermo Fisher Scientific ($TMO), who in April said that they are acquiring Life Technologies for $13.6 billion plus the assumption of $2.2 billion in debt.
In September, Eli Lilly ($LLY) showed its interest in exosomes by striking a partnership with privately-held Exosome Diagnostics, a maker of biofluid-base diagnostic tests. With the deal, Lilly gains early access to the Exosome Diagnostics’ EXO50 technology to identify expression levels in blood and gene mutations that could be connected to disease recurrence or a response to drugs.
Exosome Sciences, Inc.–Subsidiary of Aethlon Medical, Inc. ($AEMD)
Exosome Sciences is certainly noteworthy alongside its much larger peers. The company has ELLSA, an enzyme-linked lectin-specific assay that has demonstrated the ability to identify and quantify the presence of exosomes underlying human immunodeficiency virus, tuberculosis, and all forms of cancer tested to date. Aethlon’s Hemopurifier, a filtration device, has been proven to be able to capture exosomes from within the blood. Dr. Douglas Taylor has taken the position of Chief Scientific Officer at Exosome Sciences. While Dr. Taylor’s name may not sound familiar to those outside the industry, he’s a household name to those in it, as he is credited with the discovery of tumor-secreted exosomes and is a leading published author on the topic.
Interestingly, Aethlon’s founder, president and CEO James Joyce played professional football for the Denver Broncos. With very limited competition in the industry, a global leader heading up the scientific team and a connection to the NFL, it will be interesting to see what developments occur at Aethlon and Exosome Sciences in 2014, especially considering the moves this year by two majors to expand into exosome research.
Because of a strong cellular communication ability and the fact that they can to maneuver freely throughout the body, exosomes hold extreme promise as drug delivery vehicles. They are a nearly perfect biological package. Cobi Heijnen, a professor of neuroimmunology at the M.D. Anderson Cancer Center at the University of Texas, envisions being able to treat neurological conditions like Alzheimer’s by utilizing exosomes in a nasal spray. Research at the University of Alabama in 2010 showed that exosomes were capable of crossing the blood/brain barrier and reaching the neuronal cells in the brain of mouse models, even if they were carrying anti-inflammatory drugs.
Again, this all still is fairly new research, but the potential of exosomes, as well as the technologies of the aforementioned companies, is plainly evident and could revolutionize treatments for diseases and conditions that have evaded traditional therapeutic approaches. These companies are pushing the envelope in neglected areas that affect millions of people each year that are suffering from irreparable brain damage. Whether it takes the efforts and awareness created by the likes of Muhammad Ali, Michael J. Fox or the NFL, it’s encouraging that the conditions are finally receiving some extra attention.
For investors, none of the mentioned smaller companies are one-trick ponies, helping to mediate some of the risks of small and micro-cap firms. There is a long developmental road in front for each, but meeting milestones along the way should mean a lot to share value.