ALS Therapies


The only approved drug for ALS, riluzole extends survival by 2-3 months but does not have any lasting protection and is certainly by no means curative.  It’s acute effects (animal models) include:

  • decreasing persistent V-gated Na currents
  • potentiation of calcium-dependent K currents
  • inhibiting glutamate release

which all act to decrease excitotoxicity in motor neurons.

Novel Targets

1. Glutamate Transport

Ceftrixone is an antibiotic that increases glial mediated glutamate transport by stimulating expression of EAAT2.  In animal models, it prolongs life and increases EAAT2 mRNA levels.  It is currently in trials for therapeutic use.

2. Protein Misfolding and Aggregation

Heat shock proteins are involved in protein folding and degradation.  Abnormalities in HSPs promote motor neuron degeneration in ALS.  Arimoclomol is an oral drug that increases expression of HSPs involved with neuroprotective mechanisms, and delays progression and extends life in mouse models (SOD1 mutants).  It is also thought to be able to penetrate the BBB.  Clinical trials are also underway.

3. Mitochondrial Targets

Agents that improve mitochondral function (creatins) have beneficial effects in SOD1 mutant mice, but have been disappointing in trials.

Olesoxime is a mitochondrial pore modulator which also delays disease progression and prolongs survival in models.  Trials are underway.

Dexpramipexole lowers oxidative stress and maintains mitochondrial function (also extends life in models).  While it is known to be safe in humans, trials specific for ALS are underway.

Stem Cell Therapy

In theory, stem cells could be implanted to replace dying motor neurons.  However, because of the rapid progression of ALS, even if this does work, it might not work in time.

A more likely approach is to use stem cells to differentiate into non-neuronal cells that will release neuroprotective factors.

Muscle Targets

ACE-031 is a protein that inhibits negative regulators (e.g. myostatin) of muscle growth, promoting lean muscle growth and strength.  Subcutaneous treatment with ACE-031 is well tolerated in humans.

CK-2017357 activates fast skeletal muscle troponin complex by increasing its sensitivity to calcium, and thus increasing muscle force.  It is being tested in clinical trials (where it has been shown to be both effective and safe at increasing pulmonary function so far).

RNA targets

Using antisense oligonucleotides and small inhibitory RNAs to inhibit mutant SOD1 in familial ALS has therapeutic potential.  It has been shown to slow disease progress and increase survival in mouse models, and clinical trials are underway.  However, this approach will NOT help the majority of patients with the sporadic form of ALS.


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