Microparticle Therapy Offers a Glimmer of Cure for Multiple Sclerosis

The
study appears today in the journal Science Advances.

Revolutionary Promise of Microparticle Therapy

For
an unknown reason in people with MS, some of the body’s first line
of defense against foreign invaders — immune cells known as CD4+ T
cells — fail to recognize that myelin (the fatty material
surrounding and protecting nerve cells) is a normal part of the human
system.

If
these wayward, or effector T cells, become dominant, they
may provoke inflammation that damages or destroys the
myelin sheath, which in turn, can severely disrupt or curtail
transmission of nerve impulses from all parts of the body to the
brain.

“We
developed a method for ‘tipping the balance’ of the T cells
reaching the central nervous system from effectors to regulatory T
cells, or T regs, that modulate the immune system and have been shown
to prevent autoimmune reactions,” says study co-senior author
Giorgio Raimondi, Ph.D., M.Sc., associate director of the
Vascularized Composite Allotransplantation Research Laboratory and
assistant professor of plastic and reconstructive surgery at the
Johns Hopkins University School of Medicine.

“Using
this therapy on mice bred to exhibit symptoms modeling those seen in
humans with MS, we found we could enhance the growth of T regs while
simultaneously reducing the number of effectors, resulting in
reversal of the MS-like symptoms in 100% of the mice, and even more
exciting, achieving a full recovery in 38% — in other words, more
than a third were cured of their disease.”

Breakthrough Study Reverses MS-like Symptoms

The
researchers achieved these intriguing results by using biodegradable
polymeric microparticles — tiny bioengineered polymer spheres —
to deliver three key therapeutic agents: (1) a fusion of
two proteins: interleukin-2 (IL-2), which stimulates T
cell production and growth, and an antibody that blocks certain
binding sites on IL-2 to optimize the ones relevant to T reg
expansion; (2) a major histocompatibility complex (MHC)
class II molecule with a myelin peptide (protein fragment)
“presented” on its surface to immunologically select
myelin-specific (and therefore, protective of the nerve cell
covering) T regs rather than other T cell types; and (3)
rapamycin, an immunosuppressant drug that helps lower the
number of effector T cells.

“We
inject the loaded microparticles near lymphatic tissues to stimulate
the production and growth of T regs and facilitate their travel to
the central nervous system via the lymphatic system,” says study
co-senior and corresponding author Jordan Green, Ph.D., director of
the Biomaterials and Drug Delivery Laboratory and professor of
biomedical engineering at the Johns Hopkins University School of
Medicine.

“Our
study findings showed that in all of our mice, the T regs stopped the
autoimmune activity of the effectors against myelin, prevented
further damage to the nerves, and gave them the time needed to
recover.”

Furthermore,
Raimondi says, the MS-like mouse disease, experimental autoimmune
encephalomyelitis, was completely cured in more than a third (38%) of
the animals.

Promising Approach to Tackling Autoimmunity

Along
with further studies to confirm the effectiveness of their potential
MS therapy, Raimondi, Green, and their colleagues plan to try their
microparticle therapy-delivery system on other autoimmune
diseases.

“First
in line will be a mouse version of type 1 diabetes,” says study
co-senior author Jamie Spangler, Ph.D., director of the Spangler Lab
at the Johns Hopkins University School of Medicine, and assistant
professor of biomedical engineering and Chemical and biomolecular
engineering at The Johns Hopkins University Whiting School of
Engineering. “To engage and grow T regs specific for the
insulin-producing cells in the pancreas damaged or threatened by that
disease’s autoimmune activity, we’ll exchange the myelin peptide
we used in the MHC-peptide portion of the MS therapy with one from
those cells.”

“The
belief is that by simply changing the presented peptide each time, we
can target our therapy to tackle a wide variety of autoimmune
diseases,” adds Green. “We hope to have a cache of potential
therapies ready to go before moving forward to safety and efficacy
studies in mice, followed hopefully by human trials.”

Source: Eurekalert