Baby Steps

I recently came across a video of a talk given by Dr. Hans Keirstead, whose work I have mentioned in a previous post. In the video, posted June 29, 2009 (almost exactly a year ago), Dr. Keirstead showcases his research on a stem cell therapy for SMA. He shows how he was able to grow functional motor neurons (proving it by showing them innervating muscle fibers) and explaining the then-current status of a proposed human trial to replace damaged tissue. The proposed trial is for infants who suffer from Type 1 SMA. SMA (Spinal Muscular Atrophy) occurs from a malfunctioning SMN gene and the Type 1 (infantile) version is rapidly fatal. Like with a form of ALS called PMA (Progressive Muscular Atrophy), the motor neurons between the spinal cord and muscles die leaving the person paralyzed. When the diaphragm muscle is eventually denervated the person dies of respiratory failure. Regenerative medicine offers a way to replace lost tissue and restore function. In lab and animal tests it appears Dr. Keirstead has been successful. now for the next step. There seem to be good reasons to try this in SMA infants. I am going to be coldly blunt but I beg the reader to take a breath and stay with me. First, the infants are going to die very soon so the trial length is short; you will see quick benefit or have rapid access to post-mortem tissue (also the reason Neuralstem included late-stage ALS patients in its trial). Because of the infants small size, the grafted neurons don't have far to go to innervate muscle. In an adult such as myself motor neurons would have to grow a bit over a meter to reach fingers and toes. Even the phrenic nerve (the "money" nerve in neurodegenerative disease) would need to grow nearly half a meter to innervate my diaphragm muscle. Nerves grow slow so that could take as much as two years (for the more distal muscles). Infant bodies are still also in a rapid growth mode which may assist the grafts (mentioned in the Stanford study in a previous post). I could also guess that an immature immune system may be beneficial for anti-rejection purposes (pure speculation on my part). Time is in critically short supply in SMA (and ALS) so having short trial lengths is crucial. June 22, 2010 update on program progress. Because SMA is so similar to ALS, if this trial goes well it would be huge news for PALS. In fact, ALS is the next disease in line for this treatment. With this program and the concurrent ongoing programs by Brainstorm, TCA, and Neuralstem either soon to be or currently in trial, I have great hope for regenerative medicine. As always I invite responsible comments or questions.

Because Someone Has To

A few years ago a report came out claiming some fantastic results involving Lithium's efficacy in ALS. The paper was published in a respectable journal. However, reaction was surprisingly cool. Because Lithium has been used for years in much higher doses for maintenance of bipolar disorder and was cheap and easy to get, many PALS started their own off-label "trial" which collected valuable data (unfortunately to the contrary of the results of the original study). This first in history patient-driven trial forced multiple professional clinics to stage real, placebo controlled, clinical trials (with results which matched the patient-driven trial). Recently there has been interest in a natural bile acid which has anti-apoptotic effects, specifically in the mitochondria. There are two companies already in clinical trials with proprietary substances intended for mitochondrial support. Ursodeoxycholic Acid (UDCA) is found to be anti-apoptotic, easily crosses the blood-brain barrier, has an excellent safety profile, and is inexpensive and easy to obtain. A Phase 1 trial was already done which showed excellent safety for ALS patients. A few scattered PALS have been safely using UDCA and some anecdotal reports from S. Korea (using a version with a starch binder) have indicated efficacy. Unfortunately no clinic is interested in performing the trials necessary to fully investigate UDCA. So I have created the second patient-driven clinical trial intended to provide some good data on the efficacy of UDCA as a treatment for ALS. While not a true clinical trial it should be a decent indicator. I did this because the risk is low and the potential benefit high. I did this because doing nothing gets you nothing. I did this because someone has to.

Paradigm Shift

I support ALSA because of their patient services programs. My life would be more difficult without them. But I strongly support ALSTDI because they take an engineering approach to finding a cure. Throughout my life I have learned that the engineering approach is the _only_ way to properly solve a complex technical problem. I encourage you to walk for ALSA but if you want to do more than bandaid a fatal disease, strongly support ALSTDI. TDI is a paradigm shift in thinking not just about ALS but in addressing the translational research gap for orphan diseases altogether.

Insane in the Membrane

I really love the Public Library of Science because they encourage and publish research articles in the Public domain. This gives a dilettante like myself access to current peer-reviewed medical research without emptying my bank account. A couple of fascinating (if not immediately applicable) studies recently showed up in my search results. First was a study which researched how embryonic stem cells (ESCs) are not necessarily all created equal (good summary here). I rubbed that against this study which tracked how cells convert from Inner Cell Mass to ESCs. This is just basic research, so what? Well add this study from Stanford (mentioned in an earlier post) and that basic research gets more exciting. There is one company already developing methods to use placental stem cells for pharmaceutical purposes. Knowing how these cells change themselves, thereby facilitating in vitro manipulation, would be crucial. The second study demonstrated making functional neurons out of astrocytes without first reverting them to a pluripotent state (as is done with skin cells to create induced pluripotent stem cells). Sounds great, except harvesting the astrocytes can be a bit tricky. While I consider that there are multitudes from whom whole lobes could be removed with no appreciable cognitive or behavioral impact, poking holes in the brain for experimental raw material probably isn't a good idea. And the study used retrovirus to deliver the genetic information, which for in vivo application could cause problems. (apologies for the inaccurate humor stretch) While these studies don't appear to be immediately applicable to human disease (and regenerative medicine), they demonstrate how far knowledge has advanced at an extremely rapid pace. This continues to give me hope for an effective treatment very soon. While the word "soon" has been used for decades (resulting in much cynicism among PALS), the techniques explored above are extreme changes in paradigm. And as human trials with stem cell technology are already underway, the time from basic research to effective therapies is now being greatly compressed.

Stem Cell Update

In a previous post I made mention of the Neuralstem clinical trial currently ongoing at Emory University. Recently, CNN ran a story on the trial which provided welcome news to the ALS community. Three implantations had been performed with no complications so far. Today I received a press release which carried forward the good news. Based on the results so far with the first three, they are going ahead with a fourth with double the injections (both sides of the spine). This is great news as it is showing the procedure and product to be safe (the primary objective of this trial). It is still too early to determine any efficacy and the trial isn't designed to measure that anyway. With each success the barriers are pushed back a little further. The success of the Neuralstem trial will pave the way for other trials.

Advocate

Autism, Breast Cancer, Parkinson's, etc. all have internationally-recognized A-List celebrities advocating for them. As a consequence they have high public profiles with commensurate research funding levels. It is time that ALS joined the club. Hugh Laurie (Dr. House, among many other roles) would be a perfect spokesman for ALS because he has personal knowledge of its effects. If Betty White can be "drafted" to host Saturday Night Live by a Facebook page, perhaps Hugh Laurie can be drafted to be a spokesman for ALS.

Off Topic

(sort of) I resisted posting this here because it is not in keeping with the mission of this blog (I originally posted it on my Facebook page - the more proper venue). However, due to numerous requests and delays in preparing my next intended entry, here goes: My Strings Sing for Renaissance The strings To my Meat Marionette Have been cut! And so we Round up the usual suspects. As they are released One by one I realize that Lying around in bed all day Isn't as decadent as it sounds. The floppy foot Made a Goofy step As it marched up the leg. After the Fall Season I decided to have a seat. Then I Let my fingers do the walking Until they took a hike. I can't even Give myself a hand. And the creeping uneasiness Took my breath away. Unlike Mick Time is not on my side Although I seem to have more Than ever before. Now cyborg is as cyborg does And I wait for The bright near future Where once again Gravity is my friend. © 2010 Eric N. Valor