So what have we learn?!
After Luka became stable from the acute liver failure, he did every test under the sun to try and understand what caused the liver to fail. The doctors were at a loss. We would have been in a diagnostic desert without Gene sequencing. So what did we learn?
What’s happening in the body?
This disease is caused by a change (mutation) in a gene that helps control an important system inside our cells called a proton pump.
Proton pumps act like tiny regulators that control acidity (pH) inside different parts of the cell. That acidity is critical — it allows cells to make proteins, move them to the right place, and clean up waste.
When the proton pump doesn’t work properly, many systems inside the cell are affected.
PROTON PUMP
What is the proton pump?
The affected protein is part of something called a V-ATPase (vacuolar ATPase).
Think of the V-ATPase as a battery-powered pump that moves protons to create the right level of acidity inside cell compartments.
These compartments include:
the Golgi apparatus (where proteins are modified and packaged)
the lysosome (the cell’s recycling and waste center)
the endoplasmic reticulum (where proteins are made)
Each of these areas needs a very specific acidity level to work properly.
Why does acidity (pH) matter?
The right acidity inside cells is essential for:
making proteins correctly
modifying sugars on proteins (glycosylation)
moving proteins to where they need to go
breaking down waste
supporting metabolism, muscle function, and brain development
When acidity is off, proteins may be made incorrectly, misplaced, or not broken down at all..
What goes wrong in this disease?
Because the proton pump doesn’t function well:
cell compartments don’t reach the acidity they need
proteins aren’t processed or cleared correctly
waste builds up inside cells instead of being recycled
One major system affected is autophagy.
What is autophagy?
Autophagy is the body’s clean-up and recycling system.
You can think of it like this:
the cell gathers broken or poorly made parts into a “trash bag” (called an autophagosome)
that trash bag is delivered to the lysosome
the lysosome breaks it down into reusable pieces
This process only works if the lysosome is acidic enough.
When lysosomes aren’t acidic:
waste doesn’t break down properly
junk builds up inside cells
cells become damaged over time
How does this affect the body?
Over time, the buildup of under-cleared waste can lead to:
liver disease, including cirrhosis
developmental and neurological challenges
problems affecting multiple organs
Similar problems with waste buildup and lysosomal function have also been linked to age-related conditions such as Parkinson’s, Alzheimer’s, and other neurodegenerative diseases.
Why this matters
Healthy cells depend on:
proper protein production (glycosylation in the Golgi)
effective waste removal (autophagy in the lysosome)
precise control of acidity
Mutations affecting the V-ATPase disrupt all of these systems at once — which is why this disease can affect many parts of the body.
Understanding these pathways helps guide research toward therapies that support both protein processing and cellular cleanup.
OUR AIM:
To create a novel therapeutic that will address both glycosylation and autophagy issues.