Glycogen synthase

Glycogen branching enzyme

Glycogen Synthesis

GS ~ BE

↑GS Or ↓BE

↑GS Or ↓BE

Adult Polyglucosan Body Disease ↓BE

Lafora Disease ↑GS

GS ~ BE

GS ~ BE

GS

PP1

PTG

GS

PTG -/-Laforin -/-

X

PTG -/- Laforin -/-

0

0.05

0.1

0.15

0.2

0.25

0.3

1

LKODKO

GS ~ BE

PTG -/-Malin -/-

X

PTG -/- Malin -/-

Adult Polyglucosan Body DiseaseLafora Disease

Glycogen synthase

Glycogen synthase

Adult Polyglucosan Body Disease

GS ~ BE

PTG -/-GBE1 -/-

X

PTG -/- GBE1 -/-

Glycogen synthaseSmall molecule

siRNA

Amylase +/+GBE1 -/-

X

Amylase +/+ GBE1 -/-

SummaryExperiment I: GBE-/- x

PTG-/-

Will prove whether downregulating GS STOPS and PREVENTS APBD.

Will focus subsequent work on finding a small molecule that interferes with and slows GS activity.

Polyglucosan accumulation is probably a NET accumulation, i.e. the difference between their production and elimination. Potentially, stopping production could result in natural gradual elimination, and cure.

Experiment II: GBE-/- x Amylase +/+

Will prove whether introducing amylase into neurons clears polyglucosans and cures APBD.

Will focus subsequent work on finding a way to introduce amylase into the brain, ONLY ONCE. Single introduction should clear polyglucosans accumulated for 50 years and thus allow freedom from disease for the next 50 years.

Experiment III: Introducing amylase (or other) across the blood brain barrier

This experiment would be the way to actually apply the previous experiment, and introduce amylase into the brain and neurons and eliminate polyglucosan bodies.