Gene Therapy at St. Jude

Gene therapy treats genetic diseases by giving patients a healthy version of a defective gene. St. Jude is developing innovative gene therapy approaches for patients with blood diseases, immune disorders and other conditions.

GENE THERAPY:

Potential for a Cure

Graphic: What is gene therapy?

A baby is born with a defective gene, leading to a life-threatening disease. Standard therapies are limited; the child is faced with battling a chronic condition for life. 

But perhaps there is an alternative — one that may lead to a permanent cure.

Gene therapy is designed to restore the function of a patient’s defective gene by introducing a healthy copy, with the potential to permanently correct a genetic disease. This compelling concept has intrigued the medical community for more than 20 years. While still primarily performed as part of research studies, gene therapy is becoming more widely adopted for clinical treatment of some conditions.

Designing Better Gene Therapy Vectors

A major step forward has been the development of safer approaches following lessons learned from early clinical trials. In gene therapy, new genetic material (DNA or RNA) is introduced into a patient’s cells, most often via a disabled virus called a vector. The new genetic material either floats free in the cells or is inserted into the patient’s chromosomes, depending on the type of vector.

St. Jude has played a key role in vector development, pioneering innovative vector designs for patients with hemophilia and the devastating immune disorder X-linked severe combined immunodeficiency (SCID). Other vectors are in development. St. Jude has also developed exclusive manufacturing processes to produce large amounts of clinical-grade genetic material for clinical trials.

Vectors designed and manufactured at St. Jude have already helped transform the lives of patients participating in gene therapy clinical trials for immune and blood disorders.

 
 

GENE THERAPY FOR SCID:

Bubble Boy Disease

Brian P. Sorrentino, MD

Brian P. Sorrentino, MD, St. Jude Children's Research Hospital

For children born with SCID, a parent’s touch can be life-threatening. Often called “bubble boy disease,” SCID devastates the immune system and leaves patients vulnerable to lethal infections. Early death is common, even with existing therapies. 

X-linked SCID, the most common form of SCID, is caused by defects in a gene encoding a critical protein called the common gamma chain. Without it, immune system cells called T cells, B cells and natural killer cells do not develop normally. 

With the aim of pioneering a safe, effective gene therapy approach, St. Jude scientists have spent years developing an innovative vector for X-linked SCID. The vector is manufactured in the on-site Good Manufacturing Practice (GMP) facility using a process developed at St. Jude. The process, which uses stable cultured cell lines to produce the vector, addresses the challenge of manufacturing large quantities of clinical-grade vector in a reproducible manner.

The vector has been designed with features to reduce the risk of activating cancer-causing genes. It has also been subjected to extensive laboratory testing to ensure it does not readily insert into chromosomes near such genes.

We believe that this new form of gene therapy may offer X-linked SCID patients the best available treatment for their disorder.

Brian P. Sorrentino, MD, director, Division of Experimental Hematology

Clinical trials led by St. Jude and the National Institute of Allergy and Infectious Diseases (NIAID) are assessing whether this vector can safely provide long-lasting health benefits to patients with X-linked SCID.

Read about the St. Jude trial: LVXSCID-ND: Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants


 

Featured Research: Early Success for SCID Gene Therapy

In 2016, early results have been published from the X-linked SCID gene therapy trial at NIAID using the St. Jude vector. The outcomes are promising: Two years after gene therapy, the first two patients showed a high level of normal immune function. They stopped taking immune replacement therapy for the first time in their lives. Three other patients have also showed promising immune changes six to nine months after treatment.

Read full article.

Gene Therapy for Hemophilia and Other Blood Disorders

In 2014, St. Jude investigators and colleagues published historic results from a gene therapy trial for hemophilia B. A vector developed and manufactured at St. Jude had transformed the lives of young men with this inherited bleeding disorder.

Andrew M. Davidoff, MD

Andrew M. Davidoff, MD, St. Jude Children's Research Hospital

Hemophilia B is caused by defects in the gene for factor IX, a blood clotting protein. Hemophilia B can be managed with lifelong regular injections of factor IX protein, which can cost $250,000 per year.

Years after receiving a single dose of gene therapy, patients on the hemophilia B trial continued to produce their own clotting factor from the normal transferred gene with minimal side effects. The treatment dramatically decreased their need for protein replacement injections, and some were able to participate in sports without worrying about bleeding. 

The trial stemmed from a decade-long collaboration between St. Jude and University College London to discover effective gene therapies for this blood disorder. The St. Jude team was led by Andrew Davidoff, MD, chair of St. Jude Surgery and Arthur Nienhuis, MD, of St. Jude Hematology. Vector development was a critical aspect of the project, with years of careful improvements required to produce sufficient levels of factor IX to relieve symptoms.

Read about the hemophilia B study.

 
 

THE FUTURE OF GENE THERAPY:

Challenges and Opportunities

The Good Manufacturing Practice (GMP) facility at St. Jude

To date, results from clinical studies of gene therapies pioneered at St. Jude have been promising. It will be important to follow patients for many years to confirm the therapy’s long-lasting safety and health benefits. 

St. Jude researchers are now focused on applying investigational gene therapy approaches to treat X-linked SCID, hemophilia B and a related disorder, hemophilia A. The long-term vision is to apply these technologies to other genetic diseases, such as sickle cell disease, and to explore applications in developing effective immune therapies for cancer.

References

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