Motor neurons diseases

Amyotropic Lateral Sclerosis (ALS), often referred to as "Lou Gehrig's Disease", is the most common motor neuron disease with a prevalence of 2-3 per 100,000 (30,000 patients in US; 45,000 in Europe at any given time).

Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 and half of them die three to five years after diagnosis. The most common form of ALS is sporadic, but 5-10% of cases are inherited in a dominant manner (familial ALS).

Early symptoms of ALS include muscle weakness in arms and legs; later difficulties in breathing and swallowing are generally the cause of death. There is no treatment today that halts disease progression in ALS patients; the only FDA-approved drug, riluzole (marketed in the US as Rilutek®), only modestly prolongs lifespan.

Spinal Muscular Atrophy (SMA) is a disease caused by loss of function of the survival motor neuron-1 (SMN-1) gene resulting in specific loss of spinal motor neurons. Defects in this gene affect 1 in 40 people and the incidence of disease is 1 in 6,000 births.

SMA patients are divided into three subtypes depending on disease onset and severity but all suffer from degeneration of motor neurons controlling voluntary muscles with proximal limb and trunk muscle weakness leading to respiratory distress and in the most severe cases, ultimately death.

A second gene, SMN-2, can produce low amounts of functional SMN protein that partially compensates for the loss of SMN-1. Individuals with more copies of the SMN-2 gene are less severely affected, suggesting that drugs that increase production of functional protein from the SMN-2 gene could be beneficial.

Trophos Research

Trophos has developed screening assays using primary motor neurons subjected to conditions that are believed to mimic motor neuron disease: trophic factor deprivation, excitotoxicity, or mutations in the smn genes. For example, the trophic factor deprivation model uses purified motor neurons and was the basis for the identification of TRO19622 and a chemical optimization strategy that led to the synthesis of TRO40303, TRO51854 and other molecules that favour survival and inhibit death mechanisms operating in motor neurons.

Our motoneuron disease program is supported by the Association Francaise contre les Myopathies (AFM) here in France.