Tag Archives: Gene Therapy

World’s First Gene Therapy Clinical Trial for Glycogen Storage Disease Approved by FDA


Hartford, CT – This week, the U.S. Food and Drug Administration approved the world’s first gene therapy clinical trial for Glycogen Storage Disease (GSD).  This ground breaking clinical trial focusing on GSD Type Ia will be hosted by the GSD Program at Connecticut Children’s Medical Center and UConn Health under the direction of leading pediatric endocrinologist and scientist David Weinstein, MD, MMSc.WeinsteinLab-9639-300x200

Patient clinical trials of Weinstein’s gene therapy are expected to start this year in conjunction with the biopharmaceutical company Ultragenyx based in Novato, California. Connecticut Children’s and UConn Health will coordinate the trials with collaborating centers all over the world. Enrollment in the Phase 1/2 study is expected to begin as soon as next month, with data from the first cohort expected later this year.

GSD is a rare genetic childhood disorder with various forms (types 0, Ia, Ib, III, VI, IX, and XI) that impacts the liver’s storage and release of sugar. It affects one out of every 100,000 people. Healthy livers store excess sugar from food for our body’s future energy needs and release it into our bloodstream when we need it as processed sugar enzymes known as glycogen. However, in GSD, the liver fails to breakdown glycogen into glucose causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death unless there is a constant intake of glucose in the form of cornstarch. Currently, there are no approved pharmacological therapies.

GSD Type Ia, affecting an estimated 6,000 patients worldwide, is caused by a defective gene for the enzyme glucose-6-phosphatase-α (G6Pase-α) which controls sugar release from the liver.  People with this GSD disease type cannot release glucose from the liver during periods of fasting.  Hypoglycemia in GSD Type Ia patients can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, liver tumors, kidney failure, and potentially die in infancy or childhood.

The ultimate goal for the gene therapy, according to Weinstein, is to prevent low blood sugars, eliminate the dependence on cornstarch, and give patients normal lives where oversleeping isn’t a worst-case scenario. The gene therapy is administered through a single, dose injection.

“This gene therapy is designed to replace the deficient enzyme in a patient’s liver to improve glucose control and prevent the devastating short and long-term consequences of this disease,” said Dr. Weinstein, Director of the GSD program at Connecticut Children’s and UConn Health.

“It is the next step toward finding a cure, and I am personally excited that the journey towards new treatments for this condition will begin here in Connecticut.”

Weinstein’s GSD program, is a joint venture of Connecticut Children’s and UConn Health. Connecticut Children’s multidisciplinary team provides comprehensive clinical care to patients while UConn School of Medicine is home to the program’s research laboratories. This GSD Program is the largest in the world for the care and treatment of this condition.  Patients with this condition travel to Connecticut Children’s from 49 states and 48 countries for care.


World’s Top Researcher on Rare, Genetic Liver Disease Coming to Connecticut


Leading pediatric endocrinologist and scientist, Dr. David A. Weinstein and his world-renowned Glycogen Storage Disease (GSD) Program is moving to Connecticut’s UConn School of Medicine and Connecticut Children’s Medical Center in early 2017.

Weinstein’s GSD Program, currently based at the University of Florida, is the largest clinical and research program of its kind in the world. Pediatric and adult patients living with the rare, genetic liver disease travel from across the globe for his team’s expert care, a number which totals more than 500 patients from 49 states and 45 countries.

He will serve as professor in the Department of Pediatrics at UConn School of Medicine and director of the GSD Program, a joint venture of UConn Health and Connecticut Children’s. UConn Health will be home to the GSD program’s research laboratories while the multidisciplinary team will provide comprehensive clinical care at Connecticut Children’s.

“Our team is very excited to be bringing the GSD program to Connecticut at UConn School of Medicine and Connecticut Children’s Medical Center,” said Weinstein. “This is a wonderful opportunity for the GSD community, our program and our institutions.”

Weinstein and his team are on the verge of testing in clinical trial the first gene therapy for GSD, developed in conjunction with Dimension Therapeutics of Cambridge, Mass. Testing of the gene therapy has shown great effectiveness in improving the health and life expectancy of canines born with the disease.

“UConn and Connecticut Children’s is the best place to house our GSD program and launch our clinical trial research,” said Weinstein. “I am very thankful to UConn and Connecticut Children’s for thinking outside the box and their dedication to making this dream a reality. Our team looks forward to working with these outstanding institutions to find better treatments and a cure for the devastating disease of GSD.”

GSD is a rare genetic childhood disorder with various forms (types 0, Ia, Ib, III, VI, IX, and XI) that impact the liver’s storage and release of sugar. It affects one out of every 100,000 people. Healthy livers store excess sugar from food for our body’s future energy needs and release it into our bloodstream when we need it as processed sugar enzymes known as glycogen. However, in GSD, the liver fails to breakdown glycogen into glucose causing the body’s blood sugar levels to drop dangerously low leading to seizure or potentially death, unless there is constant intake of glucose.

The condition was almost always fatal until 1971 when it was discovered that continuous glucose therapy could help these patients. Cornstarch therapy was introduced as a slow release form of glucose in 1982, and it allowed feeds to be spaced to every 3 – 4 hours. Thanks to cornstarch a greater number of patients with GSD are now surviving into adulthood. However, nearly 35 years later cornstarch is the only approved treatment available.

GSD patients are high risk for other health conditions because their bodies try to compensate for the liver’s dysfunction and find alternative energy sources. The harmful complications may include: kidney stones and failure, anemia, cardiovascular disease, elevated triglycerides, high cholesterol, liver tumors (both benign and cancerous), osteoporosis and inflammatory bowel disease.

“Finding a cure as soon as possible for GSD and a way to prevent its complications is critical,” said Dr. Juan C. Salazar, chair and professor of the Department of Pediatrics at UConn School of Medicine and physician-in-chief at Connecticut Children’s. “While the consumption of cornstarch every few hours is a lifesaving treatment for GSD patients, if one dose is missed it can be quite damaging and deadly. This potential burden is too great for any parent to stomach. We look forward to Dr. Weinstein and his team’s steadfast work to further advancing care and research for GSD children and finding a cure.”

“It is simply incredible that Dr. Weinstein and eight other members of his GSD program’s team are moving to Connecticut,” says Bruce T. Liang, dean of UConn School of Medicine. “It symbolizes their true commitment, selflessness and dedication – which mirrors ours– to GSD patients and stopping at nothing to find promising new treatments.”

Members of Weinstein’s prestigious GSD program planning to join him in Connecticut include: Youngmok Lee, Ph.D., the program’s basic science coordinator; Monika Dambska, MD, the clinical-research coordinator; Ana Estrella, MD, the laboratory coordinator; Kathy Ross, RD, LDN, the dietician; and the four registered nurses Gail Butler, Iris Ferrecchia, Betsy Potocik and Emma Labrador.

“Our goal is to very soon finally find a cure for GSD and its complications,” adds Weinstein. “The strong synergies and collaborative team science happening at UConn and Connecticut Children’s is world class and the most fertile ground to make a GSD cure reality.”

“It is good to be back in Connecticut,” shared Weinstein who attended college in the state and has cared for many patients here, especially in the West Hartford community. “For the last 20 years the Connecticut community has really been supportive of my ongoing GSD clinical research work,” said Weinstein.

Weinstein graduated from Connecticut’s Trinity College and earned his medical degree at Harvard Medical School. At Boston Children’s Hospital he completed his residency, chief residency, and fellowship in pediatric endocrinology and completed his masters in clinical investigation at Harvard and MIT. He became the director of the GSD program at Boston Children’s before moving to Florida in 2005 to pursue gene therapy on dogs with naturally occurring GSD.

Prior to joining UConn Health, Weinstein served as professor of the Division of Pediatric Endocrinology at the University of Florida and director of its GSD Program. As a physician-scientist he has authored over 80 articles and 26 textbook chapters on GSD. He is the recipient of the prestigious international humanitarian award, the Order of the Smile, for helping children around the world with GSD, a recognition shared with Pope John Paul II, Mother Teresa, Nelson Mandela, and Pope Francis. Weinstein was named one of the inaugural Goldwater Scholars in 1989. He is a former Jan Albrecht Award winner from the American Association for the Study of Liver Diseases, and he received the George Sacher Award from the Gerontological Society of America. Weinstein was inducted into the Rare Disease Research Hall of Fame in 2013.

In addition to local GSD community outreach, Weinstein’s team partners internationally with institutions and scientists in Argentina, Brazil, Canada, China, Faroe Islands, Israel, Mexico, and the Netherlands.

“Dr. Weinstein’s recruitment to UConn and Connecticut Children’s is yet another example of the strong ties between the two institutions, and more importantly our commitment to providing state of the art clinical care and promoting innovative research that benefits children and adults,” said Jim Shmerling, president and CEO of Connecticut Children’s.

Dimension Therapeutics to Develop Gene Therapy Treatments for Patients with Glycogen Storage Disease Type Ia (GSDIa)


Dimension Therapeutics to Develop Gene Therapy Treatments for Patients with Ornithine Transcarbamylase (OTC) Deficiency and Glycogen Storage Disease Type Ia (GSDIa)

Severe Forms of These Diseases Have Devastating Consequences for Patients and Families, with Few or No Effective Treatment Options

CAMBRIDGE, MASS., April 23, 2015 – Dimension Therapeutics, Inc. (“Dimension” or the “Company”), a rare disease company advancing novel, liver-directed treatments for diverse genetic disorders, today announced that the company is advancing programs to treat two rare diseases with often devastating outcomes for patients and their families – Ornithine Transcarbamylase (OTC) deficiency and Glycogen Storage Disease Type Ia (GSDIa). Both diseases, due to genetically inherited inborn errors of metabolism, usually present in the neonatal period or infancy, and can have grave effects on patients of all ages. For severe forms, there are few or no effective treatment options other than liver transplantation, leaving patients with significant unmet needs. Dimension is developing novel gene therapy approaches to replace the missing or faulty gene, correcting the underlying defect to restore metabolic function.

“In an important step for both patients and for Dimension, we are launching our first two liver-associated, metabolic disease programs to address rare disorders with the greatest needs and fewest treatment options, other than liver transplant. Transplants are often associated with significant risks both during the procedure and over the long term,” said Dimension’s CEO Annalisa Jenkins, MBBS, MRCP. “Our mission – working in collaboration with patient advocacy communities and with the world’s leading clinical investigators and advisors – is to rapidly and responsibly develop new therapies that can offer hope and better health to those patients in the greatest need.”

Dimension looks forward to continuing the work previously championed by advocacy organizations, including The Children’s Fund for GSD Research, which has funded much of the existing preclinical work in GSDIa. Eric Crombez, MD, Dimension’s Chief Medical Officer, commented, “Dimension is developing and strengthening partnerships with the patient communities, families, and physicians focused on improving the lives of patients affected by OTC deficiency and GSDIa. We will ensure that patient organizations, as key partners, will play an active role in developing these clinical programs.” The company anticipates commencing clinical trials in both patient populations in 2016.

Mark L. Batshaw, MD, Principal Investigator of the Urea Cycle Disorders Consortium (UCDC) and Physician-in-Chief of Children’s National Health System, stated, “In order to solve the most pressing issues in pediatric medicine, we encourage diverse constituencies to come together in a true spirit of collaboration. This approach has been critical to the success of programs at the UCDC, and we believe it will be paramount in addressing the needs of patients and families affected by OTC deficiency.”

David A. Weinstein, MD, MMSc, Director, Glycogen Storage Disease Program at the University of Florida, noted, “Our research program, the largest of its kind pursuing treatments for GSDIa, has dedicated substantial resources to enabling gene therapy, which we ultimately believe will be the most promising approach to long-term care of

patients with GSDIa. New therapies are critically needed, and I look forward to Dimension’s progress in advancing its gene therapy program into the clinic.”

Dimension’s Adeno-Associated Virus (AAV) Vector Platform

Dimension is advancing therapies based on a next-generation AAV platform that has demonstrated early validation and compelling preclinical in vivo proof of concept across multiple disease states in leading academic research centers. Dimension’s current efforts focus on AAV8 and AAVrh10, two forms of AAV vectors that selectively target liver cells and have been optimized to deliver missing intact genes in diseases associated with the

liver. Initial indications of positive net benefit of this approach in patients living with hemophilia B, plus demonstration of robust gene expression in multiple preclinical in vivo models and commercially viable novel CMC approaches, provide a strong foundation for Dimension’s proprietary programs.

Background on OTC Deficiency and GSDIa

OTC deficiency, the most common urea cycle disorder, is caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. Individuals with OTC deficiency can build-up excessive levels of ammonia in their blood, potentially resulting in neurological deficits and other toxicities. Neonatal onset disease in males is severe and can be fatal at an early age. The greatest percentage of patients experience late-onset disease, representing a clinical spectrum of disease severity. It is estimated that more than 10,000 patients are affected by OTC deficiency worldwide. Currently, the only curative approach is liver transplantation.

GSDIa, the most common glycogen storage disease, has significant unmet needs. Patients have a defective gene for the enzyme glucose-6-phosphatase, resulting in the inability to regulate blood sugar (glucose). If chronically untreated, patients develop severe lactic acidosis, progress to renal failure, and die in infancy or childhood. There are no approved pharmacological therapies, and no ongoing clinical development beyond dietary approaches. An estimated 6,000 or more patients are affected by GSDIa worldwide.

About Dimension Therapeutics

Dimension Therapeutics, Inc., is a rare disease company focused on developing novel treatments for devastating disorders associated with the liver and based on an industry-leading, extensively validated adeno-associated virus (AAV) platform. The company is advancing multiple programs toward clinical development, including: programs addressing unmet needs for patients suffering from OTC deficiency and GSDIa; a collaboration with Bayer HealthCare in hemophilia A, and a wholly owned program in hemophilia B, which is expected to enter clinical testing in the second half of 2015. Dimension has preferred access to multiple best-in-class AAV vectors from REGENXBIO, which founded Dimension with Fidelity Biosciences in October 2013. The Dimension team and senior advisors include biotech industry veterans and renowned thought leaders in gene therapy and rare diseases. For more information, please visit www.dimensiontx.com.