and Medicine for Seniors
Key to Beating Diabetes May Be in Medicine for
Rutgers study seeks to find a safe, practical way to
diminish fat content in the liver; niclosamide may be it
5, 2014 - New research from Rutgers shows promising evidence that a
modified form of a different drug, niclosamide – now used to eliminate
intestinal parasites – may hold the key to battling the disease at its
source. Type 2 diabetes affects an estimated 28 million Americans and
almost one out of four seniors 60 and over, according to the American
Diabetes Association, but medications now available only treat symptoms,
not the root cause of the disease.
The study, led by Victor Shengkan Jin, an associate
professor of pharmacology at
Rutgers Robert Wood Johnson Medical School, has been published
online by the journal Nature Medicine.
Jin says it is important to find a suitable
medication to correct the cause of the disease as quickly as possible
because the only way now known to “cure” the disease involves major
gastric bypass surgery.
“The surgery can only be performed on highly obese
people,” Jin explains, “and carries significant risks that include
death, so it is not a realistic solution for most patients.”
And the number of patients continues to rise. The
Centers for Disease Control and Prevention projects that 40 percent of
all Americans now alive will develop type 2 diabetes.
Type 2 is the form of diabetes once known as “adult
onset,” in which the body produces insulin that ordinarily would keep
blood sugar under control, but either it does not produce enough insulin
or the body’s ability to use that insulin is degraded.
According to Jin, a major cause of insulin
resistance is the accumulation of excess fat in the cells of the liver,
as well as in muscle tissue. The fat disrupts the process where,
ordinarily, insulin would cause body tissues to correctly absorb glucose
– blood sugar – and use it as a fuel.
With nowhere else to go, much of the excess glucose
remains in the bloodstream, where in high concentrations it can damage
tissues throughout the body – potentially leading to blindness, kidney
damage, cardiovascular diseases and other severe health problems.
“Our goal in this study was to find a safe and
practical way of diminishing fat content in the liver. We used mice to
perform proof-of-principle experiments in our laboratory,” says Jin. “We
succeeded in removing fat, and that in turn improved the animals’
ability to use insulin correctly and reduce blood sugar.”
The modified medication – whose full name is
niclosamide ethanolamine salt (NEN) – burned the excess fat in liver
cells, through a process known as mitochondrial uncoupling. Mitochondria
are the microscopic energy source for each cell in the body, and
ordinarily – like a well-tuned car engine – they burn fuels including
fats and sugars in modest quantities to keep the cells functioning.
Revving up cells' internal engines to burn away
“The cell is like a car and the mitochondria are
the engine,” Jin explains. “What we’re doing inside cells is like
putting the car’s transmission into neutral by uncoupling it from the
transmission. Then you step on the gas so the engine runs full throttle
but the car doesn’t move. If too much of the fuel in the cell is fat,
you keep burning it until the fuel gauge reaches empty. Without the
interference of fat, you hope that sugar will then enter the cell
Getting rid of the interference of fat in liver and
muscle tissue is the key to restoring the cells’ ability to respond to
insulin properly, which would allow the right amount of sugar to be
taken up by cells and ultimately reverse the diabetes entirely. That
outcome is far from certain, but Jin says the positive changes he saw in
the mice are encouraging.
Jin says it also is significant that the drug he
used is a modified form of a medication that the FDA already approved
for human use. That was a deliberate choice.
“We wanted a safe and practical compound to deplete
fat inside cells,” says Jin. “We went to the literature and found an
approved drug that does in parasitic worms what we wanted to do in liver
cells. The modified form of the medication, although itself is not a
drug used in humans, has an excellent safety profile in other mammals –
so very likely it would have a good safety profile in humans too."
Also, excess fat in the liver is not just a
condition of the obese; people of normal weight can develop fatty livers
and type 2 diabetes. Jin says this kind of medication, if shown to be
effective, could safely treat patients of all weights.
Jin is cofounder of a company called Mito BioPharm,
established in 2012, which has the exclusive right to use a patent owned
by Rutgers to develop NEN for potential commercial use.
References on Niclosamide
>> “Tapeworms are treated with
medications taken by mouth, usually in a single dose. The drug of choice
for tapeworm infections is praziquantal. Niclosamide can also be used,”
reference to use of Niclosamide in
>> Reference on