CORRECT and REPLACE ASC Therapeutics, UMass Chan Medical School, and the Clinic for Special Children Announce Podium Presentation on Safety and Efficacy of Murine and Bovine Models for Novel Gene Therapy in Maple Syrup Urinary Disease

MILPITAS, Calif.–(BUSINESS WIRE)–Please replace the version dated May 16, 2022 with the following corrected version due to multiple revisions.

The updated version reads as follows:


  • First known bovine model used to demonstrate the safety and efficacy of gene replacement therapy

  • MSUD is a serious genetic disease with liver transplantation or dietary restriction as the only treatments currently available

ASC Therapeutics, in partnership with UMass Chan School of Medicine and the Clinic for Special Children (CSC), presented safety and efficacy results of a dual-function gene replacement vector therapy in mouse models and Cattle of Classic Maple Syrup Urinary Disease (MSUD) as a podium presentation at the 25th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) held May 16-19 2022 in Washington D.C.

The UMass Chan research group, led by Guangping Gao, PhD, director of UMass Chan’s Horae Gene Therapy Center, and Dan Wang, PhD, assistant professor of RNA therapy at UMass Chan, developed models mice and cattle for the MSUD with clinical expert collaboration, Dr. Kevin Strauss, MD, of the Clinic for Special Children.

Three animal models were generated to test safety and efficacy: two mouse models representing two common genetic forms of MSUD and a newborn calf naturally homozygous for a mutation that causes MSUD. All animals showed severe biochemical abnormalities within hours of birth and died within 10 days if untreated.

The partnership designed a dual-function AAV9 gene replacement vector delivered by intravenous (IV) injection. The surviving mice grew and behaved similarly to their normal counterparts and had normal or nearly normal biochemical markers on an unrestricted diet for 16 weeks.

Compared to MSUD patients, MSUD calves display a similar phenotype and are closely matched for height and metabolic rate. Without treatment, they show cerebral edema on day 3 of life and die soon after. In October 2021, an MSUD calf was born and developed biochemical signs of MSUD shortly after birth. The calf received the gene therapy vector AAV9 at 40 hours of life. After AAV therapy, biomarker measurements indicated a significant restoration of the missing enzyme activity. 70 days post-treatment, the calf is transitioned to a normal unrestricted diet and continues to thrive 100 days post-infusion with stable biochemical markers.

These data provide an early demonstration of the safety and efficacy of the MSUD AAV9 gene therapy replacement vector as a one-time treatment for the most common and severe forms of MSUD.

“The development of MSUD gene therapy builds on the combined AAV gene therapy expertise of UMass Chan Medical School, such as AAV vector design, rodent and large animal modeling, vector production at scale and in vivo preclinical testing,” said Drs. Gao and Wang commented.

Dr. Kevin Strauss, MD, Medical Director of the Clinic for Special Children in Pennsylvania, a collaborating clinical expert, added, “An innovative collaboration between the Clinic for Special Children and the Horae Gene Therapy Center at UMass Chan has allowed us rationalize the process in a thoughtful way. to develop replacement vectors for the AAV gene. In just three years after project initiation, we have safely corrected an otherwise lethal MSUD phenotype in mice and a newborn calf using a novel dual-function system BCKDHA-BCKDHB vector, which has the potential to treat 70-80% of MSUD cases reported in humans. The newborn calf with MSUD may represent the largest non-human experimental animal ever treated with AAV-mediated gene replacement. The calf provides unique information that can directly inform the design of a clinical trial, which we hope to pursue through an alliance with ASC Therapeutics. »

Dr. Ruhong Jiang, CEO of ASC Therapeutics, said: “The significant progress achieved through our research collaboration with Professors Gao, Wang and Strauss underscores the intrinsic value of bringing together highly specialized academic and industrial teams in gene therapies. complex.

About Maple Syrup Urinary Disease

Maple syrup urinary disease (MSUD) is a rare genetic disorder affecting the breakdown of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine and their ketoacid derivatives. MSUD is caused by biallelic mutations in one of three genes that code for subunits of the branched-chain ketoacid dehydrogenase complex (BCKDC), namely BCKDHA, BCKDHBand DBT. BCAA dietary restriction is the mainstay of treatment but has insufficient efficacy and offers no protection against episodic and life-threatening encephalopathy attacks. Severe (“classic”) MSUD is fatal without treatment. MSUD affects approximately 1 in 185,000 births worldwide.

About ASC Therapeutics

ASC Therapeutics is a pioneering biopharmaceutical company in the development of gene replacement therapies, in vivo gene editing and allogeneic cell therapies for hematological, metabolic and other rare diseases. Led by a management team comprised of industry veterans with significant global experience in gene and cell therapy, ASC Therapeutics is developing multiple therapeutic programs based on four technology platforms: 1) In vivo gene therapy for inherited blood clotting disorders, initially focusing on ASC618, a second-generation gene replacement therapy for hemophilia A; 2) In vivo gene therapy in metabolic disorders, initially focusing on maple syrup urinary disease; 3) In vivo gene editing, initially focusing on ASC518 for haemophilia A; and 4) allogeneic cell therapy, initially focused on deciduous stromal cell therapy for acute steroid-refractory graft-vs-host disease. To learn more, please visit

About the Clinic for Special Children

The Clinic for Special Children (CSC) is a non-profit organization located in Strasbourg, Pennsylvania that provides primary care and advanced laboratory services to those living with genetic disorders or other complex medical conditions. Founded in 1989, the organization provides services to more than 1,200 people and is recognized as a world leader in translational and precision medicine. The organization is primarily supported by community fundraising events and donations. For more information, please visit

About UMass Chan School of Medicine

UMass Chan Medical School, one of five campuses in the University of Massachusetts system, includes TH Chan School of Medicine, Morningside Graduate School of Biomedical Sciences, Tan Chingfen Graduate School of Nursing; a thriving research enterprise and innovative public service initiative, Commonwealth Medicine. UMass Chan’s mission is to advance the health and well-being of our diverse communities across Massachusetts and around the world by leading and innovating in education, research, health care delivery, and the public service. In doing so, it has earned a reputation as a world-class research institution and a leader in primary care education, permanently ranked in the top 10% of medical schools for primary care by US News and World Report. UMass Chan attracts more than $400 million annually in research funding, placing it among the top 50 medical schools in the nation. In 2021, the medical school received a $175 million gift from the Morningside Foundation and was renamed UMass Chan Medical School.

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