NIH grant Archives - Sanford Burnham Prebys

Tag: NIH grant

Institute News

Randal Kaufman included in $12 million initiative to improve hemophilia treatment

AuthorMiles Martin
Date

March 8, 2022

Randal J. Kaufman, PhD

The new project will help researchers better understanding why current gene therapy treatments aren’t working.

A multi-institute research collaboration including Sanford Burnham Prebys has just received a $12 million grant from the National Heart, Lung, and Blood Institute to improve hemophilia therapy. The award will fund three projects that could lead to safer and potentially curative treatments for the disorder. One of these projects will be led by Randal J. Kaufman, PhD, who directs the Degenerative Diseases Program at Sanford Burnham Prebys.

How viruses could be help treat hemophilia
Hemophilia is an X-linked genetic condition that prevents the blood from clotting properly. It occurs in about one out of 5,000 male births. In patients with severe forms of the disease, internal or external bleeding can be life threatening. Standard treatments for severe hemophilia involve intravenously replacing the clotting proteins that patients are unable to produce adequately on their own. However, a gene therapy approach uses viruses as a delivery mechanism to provide the body with the information it needs to start making its own clotting factors.

“Several companies have taken this forward into clinical trials, and in some of these trials, the patients initially looked like they were cured,” says principal investigator Roland W. Herzog, PhD, the Riley Children’s Foundation Professor of Immunology at Indiana University School of Medicine. “But what they all have in common is that they need to deliver a lot of the virus in order to get the desired results, and over time, clotting factor levels started to decline. So it’s clear that we need to further study the biology of this phenomenon.”

How this grant will help improve the process
In hemophilia A, which accounts for about 80% of all cases, patients do not produce enough of a clotting protein called factor VIII (FVIII). To better understand the mechanisms that are mitigating the effects of current drug candidates, Herzog is teaming up with some of the nation’s leading experts. 

Their program will focus on three major projects in gene therapy for hemophilia A:

  • Project 1 will focus on cellular toxicity and stress that can be induced by FVIII protein production. This project is led by Kaufman. 
  • Project 2 will focus on molecular virology and the development of viral vectors used in gene therapy to deliver the FVIII-encoding gene.This project is led by Indiana University School of Medicine professor of pediatrics Weidong Xiao, PhD
  • Project 3 will examine the immune system and its role in the interference of FVIII production over time. It is jointly led by Herzog and Ype P. de Jong, MD, PhD, assistant professor of medicine at Cornell University. 

Together, they hope to provide new insight that can lead to lower levels of toxicity and improved longevity of FVIII production in patients who are treated with gene therapy for hemophilia.

“This is an incredibly significant and urgent medical question, and it requires the synergy of multiple groups with different expertise to come together and solve a problem that they wouldn’t be able to solve on their own,” says Herzog. “My hope is that our studies will help the field as a whole move toward curing hemophilia A.”

The grant is titled “Toward Safer Gene Therapy for Hemophilia A” (P01HL160472). This post was adapted from a press release published by Indiana University School of Medicine.

Institute News

Sanford Burnham Prebys scientist joins historic effort to help children with rare disease

AuthorMonica May
Date

October 3, 2019

Hudson Freeze, PhD

Hudson Freeze, PhD, professor of Human Genetics at Sanford Burnham Prebys, has joined a historic effort that establishes—for the first time—a nationwide network of 10 regional academic centers, Sanford Burnham Prebys researchers and patient advocacy groups to address decades of unresolved questions surrounding congenital disorders of glycosylation, or CDG, a rare disease that affects children. The consortium is funded by a $5 million, five-year grant from the National Institutes of Health (NIH). 

“We are extremely pleased that the NIH is investing in an initiative that will improve the lives of people affected by CDG,” says Freeze, who leads efforts to develop and validate disease biomarkers that will aid in diagnoses, and measuring treatment benefits during clinical trials. “Although globally the number of people living with CDG is relatively small, the impact on the lives of these individuals and their families can be profound. We look forward to working with the patients, families, physicians, scientists and other stakeholders focused on this important study.”

CDG is caused by genetic mutations that disrupt how the body’s sugar chains attach to proteins. First described in the 1990s, today scientists have discovered more than 140 types of mutations that lead to CDG. Symptoms are wide-ranging, but can include developmental delays, movement problems and impaired organ function. Some children may benefit from a sugar-based therapy; however, developing treatments for those who need alternative treatment options has been hindered by a lack of natural history data—tracking the course of the condition over time—comprehensive patient registry, and reliable methods to establish the CDG type.

Working together, the consortium will overcome these hurdles by: 

  • Defining the natural history of CDG through a patient study, validating patient-reported outcomes and sharing CDG knowledge 
  • Developing and validating new biochemical diagnostic techniques and therapeutic biomarkers to use in clinical trials 
  • Evaluating whether dietary treatments restore glycosylation to improve clinical symptoms and quality of life

Freeze will lead the efforts to develop and validate biomarkers for CDG, working alongside the Children’s Hospital of Philadelphia and the Mayo Clinic. The principal investigator of the CDG Consortium Project is Eva Morava, MD, PhD, professor of Medical Genetics at the Mayo Clinic. The patient advocacy groups involved are CDG CARE and NGLY1.org. 

Sanford Burnham Prebys and CDG Care will host the 2020 Rare Disease Day Symposium and CDG Family Conference from February 28 to March 1 in San Diego, which welcomes researchers, clinicians, children with CDG and their families, and additional CDG community members. Register to attend. 
 

Institute News

NIH grant aims to boost heart muscle

AuthorMonica May
Date

August 23, 2019

striated muscle fibers

Heart disease is the number one killer of Americans. Now, the National Institutes of Health (NIH) has awarded a four-year grant totaling nearly half a million dollars to Sanford Burnham Prebys to find medicines that could help people repair damaged heart muscle—and potentially reduce the risk of heart attack or other cardiovascular events. 

“Each year we lose far too many loved ones to heart attacks and other heart conditions,” says grant recipient Chris Larson, PhD, adjunct associate professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys. “Now, we have the opportunity to find medicines that may help more people live long, active lives by strengthening their heart muscles.”

Nearly half of American adults—approximately 120 million people—have cardiovascular disease, according to the American Heart Association and NIH. The condition occurs when blood vessels that supply the heart with oxygen and nutrients become narrowed or blocked, increasing risk of a heart attack, chest pain (angina) or stroke. Current medications for cardiovascular disease can lower blood pressure or thin the blood to minimize risk. Still, five years after a heart attack, 47% of women and 36% of men will die, develop heart failure or experience a stroke. No medicines that repair heart muscle exist. 

To identify drugs that may stimulate heart muscle growth, Larson and his team will screen hundreds of thousands of compounds against human heart muscle cells, called cardiomyocytes. The work will be done in collaboration with Alexandre Colas, PhD, assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys, who developed the high-throughput screening system that will be employed.

Once the scientists identify drug candidates that promote heart muscle growth, they will study these compounds in additional cellular and animal models of heart disease in the hopes of uncovering insights into the biology behind the repair process. 

“After experiencing a heart attack or other cardiovascular event, many people live in fear that it will happen again,” says Colas. “Today we embark on a journey toward a future where people living with cardiovascular disease don’t have to be afraid of a second heart attack.”

Institute News

SBP researcher receives NIH Outstanding Investigator Award to study deadly pathogens

AuthorSusan Gammon
Date

June 7, 2016

Francesca Marassi

Francesca Marassi, PhD, professor in SBP’s NCI-designated Cancer Center, has been awarded an Outstanding Investigator Award from the National Institute of General Medical Sciences (NIGMS). The $4 million grant is to study how proteins on the surface of pathogens promote virulence by mediating the first-line interactions with human host cells. The project has important implications for biology and medicine.

“Our initial focus is on a protein called Ail (attachment invasion locus) that is expressed on the outer membrane of Yersinia pestis, the causative agent of plague,” said Marassi. “The Y. pestis bacterium is highly pathogenic, spreads rapidly and causes an extremely high rate of mortality. Ail is critical for suppressing the human immune defenses and for promoting bacterial invasion”

Although it is sensitive to some antibiotics, the potential use of Y. pestis as a biological weapon has led to its classification as a Tier 1 Biothreat Agent – a designation used by the U.S. Department of Health and Human Services to identify pathogens and toxins that can be misused to threaten public health or national security.

“The emerging threat of bacterial drug resistance makes our work particularly important,” added Marassi. “We will be using a technology called NMR (nuclear magnetic resonance) to determine the three-dimensional structure of Ail and examine how it associates with its human protein partners. Visualizing these biomolecular complexes helps us understand how pathogens engage their human host, and advances our ability to design effective drugs and vaccines for bacteria and viruses,” added Marassi.