High, apple pie, in the sky, hopes

“Spinal Muscular Atrophy is a motor neuron disease”

(This blog reflects research – and comments on that research – from some years back. As is logical, all things change over time.)

Although alpha motor neurons in the spinal cord remain the primary pathological target in SMA, there is now accumulating evidence suggesting that other cells, tissues, and organs contribute to disease symptoms. For example, there is now experimental evidence suggesting a non‐cell‐autonomous contribution to motor neuron degeneration from astrocytes and Schwann cells. Likewise, low levels of SMN in skeletal muscle have been implicated in SMA pathogenesis with significant disruption of the molecular composition of skeletal muscle evident in presymptomatic severe SMA mice in the absence of detectable changes in lower motor neurons. One potential unifying factor may be a deficiency in the development of vasculature in SMA; the resulting hypoxia would likely impact motor neurons as well as skeletal muscle and possibly contribute to the gastrointestinal defects (gastroesophageal reflux, constipation, and delayed gastric emptying) commonly observed in SMA patients. Although the mechanisms mediating the effects of vascular depletion have not been fully elucidated, hypoxia has been identified as a modifier of SMN2 splicing, potentially explaining some of the splicing alterations observed in SMA.

Pathophysiological findings in SMA. Multiple functional abnormalities in motor networks have been identified in SMA mice and humans, including defects in astrocytes, Schwann cells, motor neurons, and skeletal muscle. Disease‐associated phenotypes have also been reported across a range of other organs in SMA mice (in some cases supported by data from human patients), including cardiac structural and functional abnormalities, gastrointestinal tract dysfunction, and irregular bone remodeling.

SOURCE

Present treatments – either in clinical trials or already approved – work best in asymptomatic, or at best, young patients. Older patients can expect a possible detention of the progression or small improvements.

There is no cure, treatments are very, very expensive.

Stem cells are not an option for neuron replacement.

The longest efferent motor neuron directs muscle activity in the foot. Its cell body is in the basal ganglia near the brain, and its axon runs through the spine and down the leg to the foot! Can you imagine the length of a motor neuron in the giraffe?

Difference neurodegenerative pathologies and spinal lesions:

The nervous system is similar to a complex electrical circuit in which the neurons would come to be those who “give the orders” and make both “switches” and “wires”, forming nerves that transmit by electrical impulses making organs and muscles work. Hence, when the neurons or the nerves themselves are injured or degenerated, the circuit can be interrupted – and consequently, the passage of information – leaving both of them without functionality. The difference is that in neurodegenerative pathologies the circuit is interrupted because there is damage in the complete neuron, “switch” and “cable”, while in spinal injuries what is damaged is only the “cable”, the part that drives the information , leaving the “switch” intact but with the “cable” broken, that is, disconnected.