Holy smokes! I may have gotten a special advantage because of  a life-long problem I’ve had.

A little bit of context. I was born with a compromised respiratory system. Thanks to a mom who smoked non-stop from the time she was about 16 until she was almost 50. And, she only stopped then because I informed her she wouldn’t be coming to my wedding if she smoked another cigarette.

And, my beloved grandfather, Sol, succumbed to Parkinson’s disease years before. I watched as he lost his ability to write, to hold a cup of coffee, to walk, to talk over a dozen years or so. My grandfather was a willing subject (to a real clinical trial) to freeze part of his brain to alleviate his symptoms. That gave him about 5 years of respite. Which he followed by being among the very first (another clinical trial) to take L-dopa (dopamine), that provided him almost another five years. And, from there, he went downhill fast.

My two cousins, Roger and Lee (both physicians), were worried. Because the data at the time indicated that Parkinson’s skips generations. Which meant we were primed to also so succumb. Lee, unfortunately, died four years ago.  But, not from Parkinson’s. And, my cousin Roger is doing just fine. (As a matter of fact, I am looking forward to spending part of a weekend with him soon; he’s coming up to Virginia.)

Parkinson’s disease affects some 6 million folks around the globe (1 million in the USA)- and it’s the most prevalent neurodegenerative disease after Alzheimer’s.  And, like Alzheimer’s, it’s most commonly diagnosed during the 6th decade of life or later. Which is why the prevalence is about 1% of those over that age.

Data indicates that the protein, α-synuclein, accumulates in the brain cells of Parkinson’s victims. And, that accumulation seems to lead to their death. (It’s called high expression of the α-synuclein gene, or SNCA.) That’s why researchers have been seeking ways to get the compound expressed from the cranium- or, at the very least, stop the protein accumulations from clumping. (By the way, high SNCA expression is also associated with epilepsy. )

Now, back to the real subject of this blog post. Dr. Clemens Scherzer (Harvard Medical/Peter Bent Brigham Hospital) and his team (S. Mittal, X. Dong, J.J. Locascio, K.M. Abo, M. Jin, T. Bartels, D.J. Selkoe, B.J. Caladarone, V. Khurana, and M.A. Glicksman- all from Harvard/Peter Bent Brigham; K. Njornevik, A. Engeland, and T. Riise of University of Bergen in Norway; D.S. Im and D.S. Park of Ottawa, A. Flierl and B. Schule of the Parkinson’s Institute; B. Xu and Y.K. Xiang of UC Davis, J-C. Rochet of Purdue, along with P. Rizzu and P. Heutink of the German Center for Neurodegenerative Diseases) decided that examining methods that would stop α-synuclein production would be a good route to develop effective Parkinson’s therapies. So, his research group grew (human) nerve cells in the lab, so they could test the ability of a slew of materials (drugs, vitamins, dietary supplements, etc.) to preclude synuclein synthesis. It seems the key is to stimulate the β2-adrenoreceptor (β2AR) activity.

Three different drugs that they tested work just this way.   We know that β2AR is one of the cells that “relaxes” the airways.  And, these drugs (β2AR stimulants) alter the coiling of α-synuclein. One of them is salbutamol, aka albuterol- one of the most common drugs those of us who have compromised lung function have at their ready.

How did Scherzer et. al. determine how effective albuterol would be against Parkinson’s? They needed to find a bunch of people who have been larded up with albuterol for years and discern their Parkinson’s incidence.

Voila! Norway maintains a database of drug usage for its 4.6 million residents. Yet, the incidence of Parkinson’s in Norway is pretty low. Only 0.1% of those who don’t use albuterol developed the ailment. And, for those who used albuterol? Their incidence was 0.04%. After correcting the raw data for contributing factors (like age, education, etc.), they found taking albuterol once in their lives would mean they were 1/3 less likely to develop Parkinson’s. As the Scherzer team reported in Science.

However, it may be that another factor besides the direct use of albuterol  that creates this affect.   While albuterol (and related drugs) is capable of entering the brain, it could be a related affect.   Not that using albuterol would be precluded, but there may be a better choice of drug.

(This is going to get technical.  You see,  β2AR is a G protein-coupled receptor (GPCR),  SNCA is a substrate of GPCR kinases, so we could be looking at a negative regulation of dopamine neurotransmission.  And, we know that more dopamine forestalls the symptomology of Parkinson’s [that’s why L-Dopa is administered to the patients in the first place.])

Now that I got that out of the way, it’s still clear that using albuterol still provides a great advantage to those who may be susceptible to Parkinson’s disease.

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