Understanding ALS Disease Biology to Pursue Repair and Regeneration
Using Stem Cells to Improve Motor Function: Brian Wainger, MD, PhD
When motor neurons are injured, whether due to traumatic injury or neurodegenerative diseases such
as ALS, the muscle will no longer contract, and undergoes unrecoverable wasting from disuse. Preventing
this degeneration of muscle is the key factor to successful restorative nerve surgery and may lead to
improved motor function in those with ALS.
Brian Wainger, MD, PhD, is developing a novel therapy to help improve motor outcomes in nerve injury
and ALS in collaboration with Justin Brown, MD in the Department of Neurosurgery. The strategy is to
transplant engineered motor neurons that have been derived in the laboratory from human stem cells.
Such motor neurons have already shown promise in animal experiments. Motor neurons are injected
near the muscle, and the neurons then grow and
make connections to thatmuscle. These connections
have the potential to maintain muscle health and
prevent muscle wasting.
The same approach may yield benefit in those
affected by aALS. in two separate ways: first, motor
neurons injected into the phrenic nerve can supply
the diaphragm, the primary muscle for breathing. By
using an implanted cuff electrode around the
phrenic nerve, sufficiently strong respiratory function
could be maintained without the need for a
mechanical ventilator. Second, an increasingly large
number of studies suggest that a vicious cycle of
motor neuron dysfunction and muscle wasting are
responsible for disease progression. When muscle
atrophies, it can no longer provide sustenance to
nearby motor neurons, which then accelerates
motor neuron loss. By maintaining muscle
innervation, the same strategy of injecting engineered motor neurons has the potential to reduce motor
neuron loss and maintain motor function in ALS.
Brian Wainger, MD, PhD is the inaugural incumbent of the Alexander Healey
Endowed Chair in ALS at Mass General, an attending physician nd Assistant
Professor in Anesthesiology and Neurology at Harvard Medical School. His clinical
expertise spans the intersection of neurology and pain medicine. His research
focuses on understanding how the physiological properties of motor and sensory
neurons may yield insight into relevant diseases such as ALS and painful
neuropathy.
