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.
The ALS Therapy Development Institute is a non-profit biotech fully devoted to finding a treatment for ALS. A few years ago they undertook a genome-wide association study (GWAS) on the animal model of ALS (the G93A mouse).The results implicated the costimulatory pathway which links the innate and adaptive immune systems. In an attempt to address that pathway, TDI used a monoclonal antibody against CD40L. This decreased a specific T-Cell interaction which led to the body attacking the axons of the motor neurons. A very good description of the study can be found at the Alzheimer Research Forum (Alzheimers, Parkinsons, and ALS are selective neurodegenerative diseases so research in one can provide clues into the pathways of others).
This finding is interesting for a few reasons. For the first, it marks a shift in looking at ALS as a motor neuron disease to seeing it as some other dysfunction in which the neurons are injured. Second, while the treatment described isn’t a “cure”, it does point towards a significant pathway of disease management.
Another important point is the success reported by TDI. Since the development of the murine model of ALS numerous researchers have claimed varying degrees of success in preclinical work only to have the candidate substance fail in human trials. TDI undertook an internal study to figure out why and discovered numerous variabilities for which researchers must account when designing trials. TDI’s mouse program is now recognized as the “gold standard” for that model. The fact that they can report measurable and repeatable results is significant.
Of course mice aren’t men and this isn’t a cure, but it does give quite a bit of hope that a truly effective treatment may be within reach.
[UPDATE 04-02-2010: TDI discusses this via MP3 podcast.]
[UPDATE 04-05-2010: The study is now available free of charge in PDF format. Very good of Nature Publishing Group to make this available to PALS and CALS!