Finding a cure for Alzheimer's

For the last 8 months or so, I've been part of a research lab on campus.  Our lab studies acetylcholine receptors, which are proteins in the body whose function has to do with both movement and cognition, among other things.  In our research, we study the effects of another protein, beta-amyloid, on the acetylcholine receptor.  Beta-amyloid is a protein whose misfolding causes much of the pathology and neurodegeneration seen in Alzheimer's disease.  When beta-amyloid folds the wrong way, it causes other beta-amyloid copies to fold improperly as well, amplifying the degenerative effect.  We hope to characterize beta-amyloid's effect on the acetylcholine receptor to better understand the pathology of Alzheimer's.

Of course, this is only a piece of the puzzle.  Alzheimer's is a problem that encompasses many molecular players in the brain, which is why so many scientists are working on it right now.  With the scope of the problem so wide, it's hard to feel like your work is making a difference.  In fact, it may not be; it's possible that the key to curing Alzheimer's is something my current lab isn't associated with right now.  Even when labs develop drugs or other therapies that look promising for the treatment of Alzheimer's or other neurodegenerative diseases, there's still the problem of getting them across the blood-brain barrier (BBB), which excludes many molecules from entering the brain (for a good reason, of course, but it makes drug research difficult).

A couple weeks ago, for my advanced neuroscience class, we read a couple journal articles about the difficulties in getting drugs across the BBB and several ways of getting around it.  Some of them seem to do more harm than good, but more recent techniques show promise.  One of these techniques involves introducing a pathological protein like beta-amyloid with an immunologic adjuvant (an adjuvant is something that stimulates an immune response).  The adjuvant both activates the immune system and disrupts the BBB so that beta-amyloid can get across.  But why do we want to put a disease-causing protein in the brain?  Well, while the BBB is disrupted, the immune system is making antibodies against beta-amyloid.  Normally, this wouldn't matter, because if the antibodies can't get into the brain where the problem is, nothing gets solved.  But because of the adjuvant, antibodies for beta-amyloid are introduced into the brain.  And, theoretically, if we could properly introduce these antibodies without overly raising levels of beta-amyloid, it would be like a vaccine for Alzheimer's.  A VACCINE.  FOR ALZHEIMER'S.

Yep.  You heard me right.

Before anyone comes up with conspiracy theories about why this promising technology isn't already being distributed to everybody, understand that there's more that has to be done before this kind of a thing is ready to be safely and effectively used in humans.  But if this is modified to the point that it reliably and repeatedly works, it would solve one of the most expensive and debilitating medical problems in this country.  Not only solve it, but prevent it.  I haven't read much more about it since then, but it's very possible that the blood-brain barrier will be a major research focus of mine for my scientific career.  Whatever I end up doing, I want my research to help alleviate suffering.  I may just be working on a small piece of the puzzle for the rest of my life, not contributing in any noticeable way to any major problems.  But if something I discover helps somebody else to discover something that changes the world, I'm okay with that.  Because I did my part.

Cognitive enhancement

A few months ago, in my behavioral neuroscience class, one of the students was giving a presentation on "nootropics".  I had never heard this word before, but I listened with increasing interest to information about several drugs that supposedly improved attention, focus, intelligence, and even creativity.

I was no stranger to a couple of them.  I had heard of the ADHD treatment drug known as Ritalin (methylphenidate) and had known a couple of friends who had been prescribed the drug.  For a short time in high school, I was diagnosed with mild ADD and took moderate doses of Adderall to increase my focus.  The drug's initial effect was immediately noticeable:  I had intense focus throughout the day, and was more interested in some of the class material at school than I otherwise would have been (we were learning about Emily Dickinson in English that day, and...well, let's just say she's not my muse).  I also experienced the loss of appetite, feeling of stimulation, and mild insomnia that the doctor had told me was pretty likely.  Over time, I started to notice Adderall's effect less and less.  Later, I would only take it on the day of a big test or other important event; and eventually I ceased using it entirely.

This student's presentation caught my attention because it had never crossed my mind that thousands of people with no mental deficiencies whatsoever take these drugs in the hope of becoming smarter, more creative, or more mentally fit than their peers, coworkers, and competitors.  The concept of swallowing a substance to give myself an intelligence boost was intriguing.  I wrote my post about creativity shortly after this experience, spurred on by the idea that a drug might be able to make me more creative.

Noticing the excitement many people have about these "revolutionary" drugs, Hollywood's started to pander to the public's idea of smart pills.  Lucy and Limitless both toy with the idea of a drug that can unleash untold mental power (though the idea that we only use 10% of our brains is completely untrue and ridiculous).

I followed my interest in this topic until I decided to make it the subject of my undergraduate honors thesis, so I've done a fair bit of research into the objective cognitive effects of some of these drugs.  Spoiler alert:  they don't live up to the hype.  Many studies have found a significant enhancement of one or more cognitive skills by Ritalin or Adderall in healthy individuals, but the effect is usually small.  Often, when there is an effect, it is most dramatic for those who started out as low performers; proficiently intelligent people usually didn't benefit and sometimes experienced impairment with increasing doses.

Despite the evidence against the characterization of these substances as "smart drugs", many experts and ethicists push to make pharmaceuticals like these available to anyone who wants them, ADHD diagnosis or not.  Others think that widespread availability will just lead to more social inequality:  the rich will find it easier to get their hands on smart pills, and will simply become more successful while those who are unable to obtain them continue to suffer.  I'm still somewhat divided on the issue, and I'm not sure exactly what position I'll end up taking in my thesis.  Common drugs like Adderall and Ritalin aren't without their side effects; dependency is possible, and one aspiring medical student spiraled into psychosis, addiction and eventually suicide on nothing but Adderall, collected entirely under prescription by licensed psychiatrists.  Still, college students across the nation illegally obtain Adderall from peers to cram for exams or pull all-nighters to write a paper.

More recently, several drugs have come on the market that supposedly have a less severe side effect profile.  Modafinil, an FDA-approved treatment for narcolepsy, and cholinesterase inhibitors, for the treatment of Alzheimer's, are gaining underground popularity as the new generation of neuroenhancers.  Anecdotal evidence is rampant regarding individuals' experiences with these drugs and others, detailing the positive effects and the success stories.

Smart drugs are an interesting ethical issue to debate.  If a drug existed that was proven to have a significant positive impact on whoever took it, and exhibited little to no risk, would you take it?  Would you want friends and family members to take it?  How would you feel if anyone and everyone could take it?  Would you want to limit its distribution in any way?

Comment with your thoughts if you're interested.