ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) is a disease of the motor neurons — the nerves that control muscles. As the motor neurons are lost, the muscles that they control become weaker, eventually resulting in paralysis. People with ALS generally live three to five years after diagnosis, although about 10 percent live much longer.
In the past 50 years, tremendous efforts have gone into developing treatments for ALS. More than 160 clinical trials have been performed, but the result has been only one approved treatment, riluzole, which has only a modest effect in slowing the progression of the disease. This drug only increases survival by a few months. The rate of success in therapy development reflects the fact that in most cases researchers don't understand the true cause of the disease, or why it progresses
Basic research and genomics technologies are now beginning to offer some clues as to the mechanism of the disease. In January 2007, through an $18 million grant, MDA was instrumental in helping to set up the ALS Therapy Development Institute, a nonprofit research organization focused solely on ALS research. ALS TDI and other MDA-sponsored researchers have made huge steps forward in understanding the nature of the disease, and some of these will lead to potential new therapies.
Perhaps even more importantly, in 2008, ALS TDI published a seminal paper explaining why so many compounds that had been shown to affect the progression of ALS in mouse models failed to work in clinical trials. This work will allow drug development in ALS to be performed in a much more efficient manner.
As of 2012, 62 companies have a product in development for ALS. Strategies for treatments include:
- Anti-excitotoxic compounds that are designed to reduce toxic compounds such as glutamate
- Anti-inflammatory compounds that are designed to decrease the inflammation that occurs around dying motor neurons
- Antioxidant compounds that are designed to protect neurons
- Neuroprotective compounds selected because they protect motor neurons from damage
- Anti-apoptotic compounds that prevent cell death
- Anti-aggregation compounds that break down the clumps of protein that form inside cells in ALS patients
- Growth factors that are hoped to encourage growth of motor neurons and prevent degeneration
- SOD1 reduction techniques that aim to reduce the levels of the protein that is mutated in some inherited forms of ALS
- Various techniques whereby muscles can be strengthened even in an environment where motor neurons are degenerating, thus maintaining motor function.
- Gene therapy techniques that are generally used to get patient cells to produce growth factors.
- Stem cell therapies that are designed to either support existing motor neurons, and/or to replace them with new motor neurons
Many of the drugs in development for ALS also may have uses in other diseases. ALS drugs in development also are being tested for use in Friedreich's ataxia, Charcot-Marie-Tooth disease, multiple sclerosis, Parkinson's disease, etc.
MDA's Translational Research Program was supporting Washington University to plan and run a phase 1 study for a treatment designed to remove, or "block," the mutated protein which causes the most common inherited form of ALS. This project is now running in collaboration with Isis Pharmaceuticals, and a phase 1 trial is nearly completed.
MDA, through its Augie's Quest research initiative, is funding the ALS Therapy Development Institute to investigate several different therapeutic avenues, including gene therapies and immune modulation drugs. MDA awarded ALS TDI a $2 million grant in 2012, following on from more than $24 million invested previously.
In 2012, MVP invested in several additional ALS programs:
- MVP awarded $268,000 to Glialogix to test a small molecule therapy previously tested for other diseases in the mouse model of ALS.
- MVP awarded $250,000 to ALS Biopharma to study its Hsp70-based therapy for ALS. The company will determine if it can improve delivery of the protein to the necessary tissues to be effective in treating ALS. This project has been terminated due to milestone failure.
- MVP awarded $278,850 to ALS TDI to test the mouse version of an existing drug in the mouse model of ALS.