attack life-saving drugs
Treatment prevents development of antibodies against drugs for hemophilia
A and Pompe disease; could be applied to autoimmune disorders and allergies


Date:
September 30, 2021
Source:
University at Buffalo
Summary:
Researchers have developed a new treatment that uses reverse
vaccination to pre-expose the body to medications and build immune
tolerance. The treatment could be applied to a broad range of drug
therapies, autoimmune disorders and allergies.



FULL STORY ==========================================================================
For nearly a third of patients with hemophilia A and almost all patients
with Pompe disease, their own immune system is their greatest obstacle
to treatment.

When given essential proteins and enzymes, their body perceives the
treatments as a threat and attacks.


========================================================================== However, University at Buffalo researchers have developed a new treatment
that uses reverse vaccination to pre-expose the body to medications and
build immune tolerance. The novel treatment pairs essential proteins
and enzymes with lysophosphatidylserine (Lyso-PS), a fatty acid that
helps the immune system tolerate foreign substances, reducing adverse
reactions to the drugs.

Unlike traditional vaccination, which uses pre-exposure to teach the
immune system to attack potential threats, reverse vaccination uses
exposure to teach the immune system to ignore foreign substances. The
treatment could be applied to a broad range of drug therapies, autoimmune disorders and allergies, says lead investigator Sathy Balu-Iyer, PhD,
professor of pharmaceutical sciences and associate dean for research in
the UB School of Pharmacy and Pharmaceutical Sciences.

The results were published this month in Scientific Reports. Balu-Iyer
recently received funding to continue preclinical research from the Empire Discovery Institute, which will license the technology and advance the treatment to the market.

"The safety and effectiveness of several life-saving therapeutic drugs are compromised by anti-drug antibodies. Once antibodies develop, clinical
options available for patients become expensive and, in several cases, ineffective," said Balu-Iyer.

"Instead of attempting to reverse the anti-drug antibodies, which
is highly challenging, clinical treatments that prevent antibody
development may be a more effective strategy," says Nhan Hanh Nguyen,
first author and pharmaceutical sciences graduate student at UB. "Our
approach is based on the rationale that pre-exposure of a protein in the presence of Lyso-PS teaches the immune system not to mount a response." Hemophilia A is a genetic bleeding disorder caused by the lack of blood- clotting protein Factor VIII. Patients with the disorder are at severe
risk for bleeding after injury or surgery. Recombinant Factor VIII is
the first line of defense in treatment, however, the body may associate
Factor VIII with other threats and produces antibodies that destroy it. A
third of patients experience these adverse reactions, and once antibodies develop, the cost of clinical treatments may rise above $700,000 per year.



==========================================================================
For Pompe disease, a rare genetic condition in which the body lacks the
enzyme necessary to break down complex sugars for energy, more than 90%
of patients develop antibodies to treatments. Without the enzyme, acid
alpha glucosidase (GAA), sugar builds up in the muscles and organs,
causing weakness and shortening life expectancy. Attempts to suppress
the immune system expose patients to risk of secondary infection.

Findings published in August in the Journal of Thrombosis and Haemostasis
found that four weeks of co-administration of Lyso-PS with Factor VIII significantly reduced the development of antibodies without impacting
the effectiveness of the protein.

The new research designed and tested a Lyso-PS nanoparticle with the
ideal size and surface characteristics for cellular uptake, binding and survival in the digestive tract.

The study found that the designed Lyso-PS nanoparticle prevented the development of antibodies against Factor VIII in 75% of subjects, and significantly reduced antibody levels against GAA.

The treatment was effective when delivered intravenously as well as
orally, the latter of which could allow for easier consumption and
improved medication compliance by patients, says Balu-Iyer.

Additional investigators on the September study include Fiona Glassman,
PhD, senior clinical pharmacologist at CSL Behring, and Robert Dingman,
PhD, at Regeneron Pharmaceuticals, both former students in Balu-Iyer's
lab; Gautam Shenoy, PhD, research scientist in the Jacobs School of
Medicine and Biomedical Sciences at UB; Elizabeth Wohlfert, PhD, assistant professor of microbiology and immunology in the Jacobs School; Jason Kay, associate professor of oral biology in the UB School of Dental Medicine;
and Richard Bankert, VMD, PhD, professor of microbiology and immunology
in the Jacobs School.

========================================================================== Story Source: Materials provided by University_at_Buffalo. Original
written by Marcene Robinson. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Nhan H. Nguyen, Fiona Y. Glassman, Robert K. Dingman, Gautam
N. Shenoy,
Elizabeth A. Wohlfert, Jason G. Kay, Richard B. Bankert, Sathy
V. Balu- Iyer. Rational design of a nanoparticle platform for
oral prophylactic immunotherapy to prevent immunogenicity of
therapeutic proteins.

Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-97333-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210930104849.htm

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