p75 as a Biomarker for ALS / MND

You may remember the ice bucket challenge. And the cause behind it, Amyotrophic lateral sclerosis (ALS) (for a very good editorial on this, have a look here).

ALS or Motor neuron disease (MND) is a disease characterised by progressive, debilitating paralysis from loss of motor neurons in the cerebral cortex, brain stem and spinal cord and is almost always fatal. The average life expectancy following diagnosis is just 36 months with, most often, patients succumbing to the disease because of denervation of muscles involved in respiration. There is only one therapeutic option for patients, a Glutamate antagonist, riluzole, which offers a modest 3–6 month extension in survival.

Objective biomarkers for ALS would facilitate the discovery of new treatments. Recent published work on p75NTR Neurotrophin Receptor has now added evidence for its use as a Biomarker for ALS / MND.

The Nerve Growth Factor Receptor (NGFR), also known as p75 neurotrophin receptor, is a common receptor for the neurotrophins NGF, BDNF, NT-3 and NT-4/5.

In neurons, p75NTR mediates a variety of physiological functions including survival, apoptosis, neurite outgrowth and synaptic plasticity. The extracellular domain of neurotrophin receptor p75 was identified in the urine of ALS patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75.

Pilot data of disease progression rates in ALS patients indicates that p75NTR^ECD levels were significantly higher in rapidly progressing patients as compared to patients with slowly progressing disease. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in ALS.

This ELISA is now commercially available for serum, cell culture supernatants and brain extracts. The ELISA renders results less than 4 hours, and is available for human and mouse. Antibodies are also available for human and rat.

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