In a previous article, I discussed the current state of treatments for Alzheimer's disease, which is the sixth leading cause of death in the United States. Companies such as Eli Lilly (NYSE:LLY), Johnson & Johnson (NYSE:JNJ), and Pfizer have tested various treatments targeting protein fragments known as beta-amyloids, which can build up on brain cells like rust -- causing their degeneration.
Unfortunately, none of these treatments have worked, and researchers still aren't certain that removing or halting the formation of beta-amyloid plaques -- despite being identified as one of the hallmarks of the disease -- is the most effective approach. Johnson & Johnson, for example, recently signed an agreement with Evotec to go back to the drawing board to test solutions on the molecular level, rather than take another swing at beta-amyloids.
Therefore, thinking outside the beta-amyloid box might be a good idea for Alzheimer's researchers. In this article, I'll discuss three fascinating alternative treatments to the disease using currently approved drugs -- and how they could also pull companies like Novo Nordisk (NYSE:NVO) and Amgen (NASDAQ:AMGN) into the market.
Blood pressure treatments
A recent study conducted at Johns Hopkins University revealed that blood pressure medications reduced the risk of Alzheimer's disease by 50%, based on data gathered from a group of 2,200 adults between 75 and 96 years of age.
The discovery was accidental -- the patients had originally enrolled for the program to determine if the herb ginkgo biloba could reduce the risk of Alzheimer's. Although the herb was found to be ineffective, researchers noticed that patients who regularly took blood pressure medications -- such as ACE inhibitors, ARBs, and diuretics -- had a much lower risk of Alzheimer's dementia.
ACE inhibitors constrain the production of a blood pressure regulating enzyme known as angiotensin II, which causes blood vessels to contract. Novartis' Lotensin and Par Pharmaceutical's Capoten are well-known ACE inhibitors.
ARBs also target angiotensin II, but try to keep the enzyme from binding to receptors on blood vessels, rather than preventing their production. Commonly prescribed ARBs include Sanofi's Avapro and AbbVie's Teveten. Meanwhile, diuretics such as Lasix increase urine production, which triggers other mechanisms which can lower blood pressure.
For now, the unexpected correlation between blood pressure drugs and Alzheimer's has perplexed researchers, and will inevitably be the subject of future studies.
Another surprising alternative treatment for Alzheimer's disease is Novo Nordisk's diabetes drug Victoza, which has been tested at Lancaster University as a potential treatment. The researchers believe that Victoza could possibly reverse memory loss in late-stage Alzheimer's disease and prevent the buildup of beta-amyloid plaques.
Victoza is a GLP-1 analog, a new class of drugs that stimulate natural insulin production in diabetes patients. The applications in diabetes are obvious -- they can reduce the number of necessary daily insulin injections and substantially improve the lives of patients. Victoza has become one of Novo's main pillars of growth -- during the first nine months of fiscal 2013, sales of the drug climbed 28% year over year, accounting for nearly 14% of its total revenue.
For the Alzheimer's study, Victoza was tested on 14-month old mice suffering from late stage Alzheimer's. The drug was injected into the mice over a two-month period, after which their brains showed a 30% reduction in beta-amyloid plaques. The study also showed that Victoza could cross the blood-brain barrier to protect brain cells, allowing them to better handle stress and toxins.
As a result of the successful test, a new human clinical trial is under way, led by Dr. Paul Edison of Imperial College London, and could have major implications for the GLP-1 market.
A new opportunity for Eli Lilly
If Victoza shows promise as an Alzheimer's treatment, it could ironically represent a new opportunity for Eli Lilly, which has racked up some major losses chasing its Alzheimer's dream over the past two years.
Eli Lilly's investigational GLP-1 drug for diabetes, dulaglutide, has shown promising safety and efficacy results during phase 3 trials. If approved, it will be the third GLP-1 drug on the market, joining Victoza and Byetta/Bydureon from AstraZeneca and Bristol-Myers Squibb. Peak sales estimates for dulaglutide run as high as $1.7 billion by 2020.
If Victoza shows continuing promise as an Alzheimer's treatment, it's likely that interest will also shift toward dulaglutide and Byetta/Bydureon for the same indication.
Rheumatoid arthritis treatments
Last but not least, rheumatoid arthritis treatments -- which include some of the biggest blockbuster drugs on the market -- could also be viable treatments for Alzheimer's disease.
A new study scheduled to start next year will attempt to use Enbrel -- Amgen's blockbuster arthritis treatment which generated $4.2 billion in sales last year -- to treat Alzheimer's disease. Clive Holmes, a psychiatrist at the Memory Assessment and Research Center at the University of Southampton, is leading the study, which hypothesizes that anti-inflammatory drugs could have a favorable impact on Alzheimer's patients.
Enbrel blocks TNF-alpha, a signalling molecule that immune cells use to communicate with each other. Blocking TNF-alpha reduces inflammation, making it a popular treatment for inflammatory conditions like rheumatoid and psoriatic arthritis. However, studies have shown that the beta-amyloid buildup that previous treatments had targeted did not address the inflammation that was caused by the body's immune response to the plaques. Therefore, although the brain plaques were removed, the damage persisted due to the TNF-alpha response.
If Holmes' theory proves feasible in an upcoming pilot trial, he plans to conduct a clinical study on patients with the earliest forms of the disease. This is a fascinating new approach which means that other top-selling TNF-blocking treatments, like J&J and Merck's Remicade and AbbVie's Humira, might also have potential as Alzheimer's treatments.
The Foolish takeaway
When a problem can't be solved, it's always wise to think outside the box, especially when the Centers for Disease Control and Prevention projects that cases of Alzheimer's will nearly triple by 2050. Beta-amyloid treatments were once considered to be the brightest hope in treating Alzheimer's, but it's becoming increasingly clear that new methods should also be explored.
Therefore, it's encouraging that researchers have gone back to test existing treatments like blood pressure, diabetes, and arthritis drugs to fight this debilitating disease, which could lead to some unexpected discoveries down the road.