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MOTOR NEURON DISEASE (MND)
Clinical
Motor neuron disease (MND), also known
as Lou Gehrig’s Disease or ALS, is a devastating
neurodegeneration in which progressive dying away of any
combination of the motor neurons, anterior horn cells or
corticospinal tract results in progressive wasting away
of all of the muscles over several years, culminating in
a wheelchair bound patient unable to speak, swallow and
eventually breathe. It affects 1 in 50,000 of the population.
It is part of a group of motor system degenerations which
include Spinal Muscular Atropy (SMA), the commonest fatal
inherited disease in childhood after cystic fibrosis.
Approximately 10% of human ALS/MND are
inherited, while 90% are sporadic, with unknown cause.
Research over the last ten years has been primarily driven
by the discovery of mutations within the SOD1 gene being
linked to a dominantly inherited form of ALS/MND. Mutations
in the SOD1 gene are complex as over 100 mutations have
thus far been reported. The precise mechanism by which
such mutations contribute to disease onset and pathology
remain unresolved.
Such is the desire to identify a therapeutic
agent, many drugs have been pushed into clinical trials
to try and halt disease progression, including free radical
scavengers, copper chelators, antioxidants, anti-inflammatory
drugs, exogenous and transfected neurotrophic factors,
anti apoptotic drugs, caspase inhibitors and riluzole.
Of these treatments, those that inhibit oxidative mechanisms
have been found to temporarily delay disease onset, yet
do not increase survival, whilst those agents inhibiting
glutamatergic or apoptotic mechanisms temporarily increase
survival time but do not affect onset. The only approved
drug currently available is riluzole, a glutamate antagonist.
Despite only having been shown to have a modest short term
effect, it is routinely prescribed in the US and has been
approved by NICE in the UK.
DanioLabs approach
DanioLabs is identifying therapeutics which
improve motor neuron function and survival. Compounds
which are additive or synergistic to riluzole and which
show a large clinical effect are being prioritized.
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