Axon-Axoff

Why do axons go downhill? Gravity has nothing to do with it... The linked study, though not specifically aimed at ALS, does seem to tie together a few "hot topics" in the pathology: axonopathy, oxidative damage, and mitochondrial dysfunction. With many plausible theories of damage, trying to link some together may provide more clues as to cause and/or (more importantly) ways to effectively treat the disease. Part of the tie to ALS in this study is the fact that mice bred to lack the SOD1 gene exhibit a similar disease process as mice bred with a copy of the malformed SOD1 gene which is a known cause of familial ALS. Reinserting the gene in the "knockout" mice, but only in the mitochondria, rescued the mice from disease. Mitochondria are the power plants of the cells and as a consequence also produce molecules which can cause cellular damage (ROS, the "industrial waste" of cellular energy production). Anything which disrupts the ability to clear out this waste can cause damage to the cell. Damage to mitochondria impacts their ability to provide energy to the cell. Motor neurons have high energy requirements and due to their extremely long axons have mitochondria operating at large distance from the cell body. There are currently a few clinical trials going into Phase III aimed at mitochondrial support. While the study doesn't provide an answer (except that this problem is "way beyond eating blueberries"), it does provide some important clues for further investigation.

More Baby Steps

In June I posted a discussion about a prospective regenerative therapy. On December 1, I received a press release that the company developing this therapy has filed an IND with the FDA. This is a huge step forward for people suffering from motor neuron disease (especially late-stage PALS like myself). However, it is but the first baby step in the clinical trial journey. Let's hope that the FDA acts swiftly and positively on this IND.

Medical Tourism

It's been over a month since my last post. A couple of interesting things have come over the transom but nothing really compelling for me to write about. Also I have been busy in other areas. Something compelling did show up today. An article on Nature Magazine's website concerning the controversy around stem cell medical tourism and the difficulty in regulation. While stem cells offer tremendous potential, the science necessary to fully and safely exploit that potential is still in its infancy. However, because of the potential, the desperation of people afflicted with horrible disease, and the ability to conjure and proliferate medical buzzwords over the Internet, the unwary and uninformed are preyed upon by the immoral and unscrupulous. As can be demonstrated by reading my previous entries, I am a firm believer in stem cell technology. I am anxious to participate in one or more procedures in the hope of regaining function. But the science needs a little more time to develop. Anyone offering or advocating a stem cell "therapy" is either lying or deluded. Several clinical trials are underway or will soon commence (some of which I have previously discussed). But for now, I urge the reader to save your money and preserve your health by not succumbing to the siren song of an exotic "miracle cure".

Stop the Pop

Apoptosis is an important function in multicellular organisms such as people. It keeps cancer at bay and helps keep organs healthy and fresh. But when it occurs in cells that aren't replaced (like motor neurons) nasty things (like ALS) happen. A couple of clinical trials are currently ongoing to support the mitochondria to delay apoptosis (Knopp with dexpramipexole and Trophos with olesoxime). Recently, a study was published which took a rather more aggressive approach. The approach probably isn't appropriate as a therapeutic because it isn't cell-specific. For a good explanation, please read Amber Dance's article over on the ALZ Forum. Ms. Dance is one of my favorite science writers and actually has some credentials to back up her analysis.

Stem Cell Update

Today (10/12/2010), Geron began a Phase-I clinical trial using embryonic stem cells to treat spinal cord injury. While not directly applicable to ALS, a successful safety trial should open up approvals for similar subsequent trials utilizing human embryonic stem cells. Already there is favorable preliminary information coming from the Neuralstem trial (which uses fetal neural precursors, not embryonic stem cells) and several more are in the approval pipeline. Meanwhile, in Israel, Brainstorm received approval to begin its trial for ALS. As discussed previously, Brainstorm engineers autologous cells to secrete neural growth factors and then implants them in muscle to promote axonal growth and nourish the cell body via axonal uptake. It's a novel approach which doesn't require risky surgery. These are just a few very interesting things going on in research and clinical trials. But keep in mind that they are happening now.

National ALS Registry

The United States National ALS Registry opened this month. There is an introductory page on the ALSA website, and a recorded webinar outlining the Registry can be replayed by clicking here. I believe it is the duty of each PALS to register so that finally accurate numbers can be known of the toll of ALS in the US. The oft-quoted "30,000" is a very rough estimate and in all likelihood much too few. This is an important tool too long missing from researchers' kits. I registered yesterday. How about you?

Laser Focus

For many years now, part of the fight against ALS has been focused on finding reliable biomarkers. This has proven difficult as there is so much variability in progression and phenotype. However, what if you had something better than a biomarker? How about direct observation of the motor neurons and the neuromuscular junctions. This is a sales video of the type of device used (a confocal microendoscope). And here is a news video with the device being used in diagnosis of another condition.The ability to live-image, in-vivo, down to the individual cellular level is super cool and is nearly "Star Trek" in terms of nifty. Professor Richard Ribchester is the person leading the work. This tool may be enormously helpful in studying neurodegeneration and in gauging efficacy of any experimental drugs or treatments.