JCR Pharmaceuticals Showcases Preclinical Gene Therapy Findings Demonstrating Strong CNS Uptake at the American Society of Gene and Cell Therapy 29th Annual Meeting
JCR Pharmaceuticals presented new preclinical findings highlighting the potential of its proprietary JUST-AAV gene therapy platform during the American Society of Gene and Cell Therapy 29th Annual Meeting, held in Boston, Massachusetts. The presentations showcased a series of experimental studies demonstrating the platform’s ability to improve delivery of gene therapies to the central nervous system while reducing unwanted accumulation in the liver, a longstanding challenge associated with conventional adeno-associated virus-based therapies.
The company’s presentations included oral and poster sessions detailing investigational approaches for severe neurological disorders such as GM1 gangliosidosis and neuronal ceroid lipofuscinosis, also known as CLN disease. In addition, Alexion, part of AstraZeneca, shared collaborative preclinical research utilizing JCR’s JUST-AAV technology in a separate oral presentation.
The data collectively underscore growing industry interest in next-generation gene therapy delivery systems capable of overcoming biological barriers that have historically limited the effectiveness and safety of gene transfer technologies targeting neurological diseases.
Adeno-associated virus vectors have become one of the most widely used delivery vehicles in gene therapy development because of their ability to transport therapeutic genetic material into cells. However, traditional AAV vectors such as AAV9 can face several limitations, including insufficient penetration into the brain and central nervous system, high liver exposure, immune-related concerns, and challenges achieving broad tissue distribution after systemic administration.
JCR’s investigational JUST-AAV platform was designed to address these issues through engineered vector capsids optimized for targeted tissue delivery. The platform includes multiple vector variants focused on different therapeutic applications, including liver-sparing, muscle-targeting, and brain-targeting approaches.
According to the company, the technology aims to improve both the efficacy and safety profile of AAV-mediated gene delivery by enhancing transgene distribution into disease-relevant tissues while reducing off-target accumulation, particularly in the liver.
Hiroyuki Sonoda, President and Chief Scientific Officer of JCR Pharmaceuticals, stated that the new preclinical findings demonstrate the ability of the company’s novel capsid technologies to deliver therapeutic agents to the central nervous system more efficiently than conventional AAV9 vectors while simultaneously decreasing liver accumulation.
Sonoda noted that the results represent progress toward potential therapies for difficult-to-treat neurological disorders and reinforce the company’s commitment to advancing innovative treatment approaches for severe neurodegenerative diseases.
One of the featured presentations focused on the development of an AAV-based investigational therapy for GM1 gangliosidosis, a rare inherited lysosomal storage disorder caused by deficiency of the enzyme β-galactosidase. The disease leads to accumulation of GM1 gangliosides in the brain and other tissues, resulting in progressive neurodegeneration, severe neurological impairment, and early mortality.
The oral presentation, delivered by Saki Matsushima of the The Jikei University School of Medicine, described a novel strategy combining liver-directed AAV gene therapy with a transferrin receptor-targeted, blood-brain barrier-penetrating enzyme construct.
Researchers engineered a plasmid encoding β-galactosidase fused to an antibody-derived transferrin receptor-binding domain. This design was intended to exploit receptor-mediated transport mechanisms across the blood-brain barrier after systemic administration, enabling therapeutic enzyme delivery into the central nervous system.
In preclinical mouse models of GM1 gangliosidosis, intravenous administration of the investigational liver-specific AAV vector produced strong hepatic expression and elevated circulating levels of the engineered enzyme. The TfR-targeted β-galactosidase subsequently distributed efficiently to peripheral tissues and the brain.
The experimental therapy markedly reduced GM1 ganglioside accumulation in brain tissue and produced meaningful neurological improvements in treated animals. Researchers also reported significantly prolonged survival compared with untreated disease models.
Importantly, investigators demonstrated comparable biodistribution, central nervous system penetration, and therapeutic efficacy in humanized GM1 mouse models expressing human transferrin receptors. This finding is considered particularly relevant for translational development because it supports the feasibility of adapting the strategy for potential use in human patients.
The researchers reported that no apparent toxicity related to hepatic transgene expression or systemic enzyme exposure was observed during the preclinical studies.
According to JCR, the findings provide proof-of-concept evidence that AAV-mediated expression of transferrin receptor-targeted lysosomal enzymes may enable robust correction of neurological pathology in lysosomal storage disorders characterized by central nervous system involvement.
Another major presentation highlighted the long-term efficacy and neuroprotective effects of systemically administered JUST-AAV therapies in preclinical models of neuronal ceroid lipofuscinosis, including CLN1 and CLN2 disease.
Neuronal ceroid lipofuscinoses are a group of rare inherited neurodegenerative disorders commonly referred to as Batten disease. These conditions are characterized by progressive loss of motor and cognitive function, seizures, vision impairment, and premature death due to accumulation of lysosomal storage material within cells.
In the CLN1 disease study involving PPT1 deficiency, researchers compared outcomes across multiple experimental groups, including untreated controls, recombinant enzyme replacement therapy, conventional AAV9-mediated therapy, and JUST-AAV-based treatment.
The untreated disease control group and animals receiving recombinant PPT1 enzyme replacement therapy showed no survival benefit, with deaths occurring between weeks 31 and 41. Mice treated with conventional AAV9-PPT1 demonstrated improved survival extending into weeks 53 through 65.
However, animals receiving the investigational JUST-AAV-PPT1 therapy experienced survival durations approaching those of healthy wild-type control animals, representing a substantial improvement compared with both conventional approaches and untreated disease controls.
The study also demonstrated meaningful reductions in neuropathological markers associated with lysosomal storage and neuroinflammation. Investigators observed decreased areas positive for SCMAS, CD68, and GFAP, biomarkers commonly associated with inflammatory activation and disease progression in CLN disorders.
Brain tissue analysis confirmed elevated PPT1 enzyme activity in JUST-AAV-treated mice, supporting successful gene transfer and sustained therapeutic expression within the central nervous system.
Researchers additionally reported preservation of locomotor function in treated mice at 54 weeks of age, with motor performance described as nearly indistinguishable from healthy control animals. Retinal integrity was also preserved, with significant protection against retinal ganglion cell layer thinning compared with diseased untreated animals.
In a parallel CLN2 disease study involving TPP1 deficiency, systemic administration of JUST-AAV-TPP1 similarly produced substantial therapeutic benefits. Investigators reported survival outcomes approaching those observed in healthy control animals, along with elevated TPP1 enzyme activity in brain tissue during post-mortem analyses.
According to JCR researchers, the findings collectively demonstrate that JUST-AAV-mediated therapies can efficiently deliver transgenes to the central nervous system following systemic administration while producing long-term therapeutic effects in severe neurodegenerative disease models.
The company stated that these preclinical results support the broader potential of the JUST-AAV platform as a next-generation gene therapy approach for lysosomal storage disorders and other CNS diseases.
Separately, Alexion presented additional collaborative preclinical findings involving a transferrin receptor-targeted JUST-AAV capsid incorporating a miniaturized anti-TfR antibody binder displayed on the capsid surface.
The engineered capsid also included sequence modifications designed to minimize liver exposure, one of the major limitations associated with many traditional AAV vectors.
Following a single intravenous administration in both mouse models and non-human primates, the investigational capsid demonstrated broad central nervous system biodistribution while achieving higher brain-to-liver exposure ratios relative to conventional AAV9 vectors.
Researchers additionally observed dose-dependent transgene expression and favorable tolerability profiles in the preclinical models studied.
According to the presentation, the findings support the translational potential of the platform for achieving widespread brain distribution while reducing liver accumulation, an important consideration for improving the therapeutic index of systemically delivered gene therapies.
The ASGCT presentations come amid increasing industry focus on improving the precision, safety, and efficiency of gene delivery technologies. While multiple AAV-based therapies have already reached the market for rare genetic diseases, limitations involving immune responses, insufficient tissue targeting, and dose-related toxicities continue to challenge the field.
New vector engineering strategies such as JCR’s JUST-AAV platform seek to overcome these barriers by optimizing capsid structure and biodistribution characteristics for specific therapeutic applications.
For neurological diseases in particular, successful delivery across the blood-brain barrier remains one of the greatest challenges in gene therapy development. Conventional systemic AAV administration often results in substantial liver exposure while only limited quantities of therapeutic material reach the brain.
The transferrin receptor-targeting strategies presented by JCR and Alexion are part of a broader scientific effort to harness endogenous receptor-mediated transport mechanisms to improve central nervous system access for biologic therapies.
Although the findings remain preliminary and derived from preclinical research, the data presented at ASGCT 2026 contribute to growing evidence that engineered next-generation AAV platforms may significantly expand the therapeutic possibilities for severe neurological and neurodegenerative disorders.
JCR emphasized that the studies remain investigational and that limitations of the preclinical models were not discussed during the conference presentations. Nonetheless, the company believes the emerging data provide important translational support for advancing these technologies toward future human clinical development.
About the American Society of Gene and Cell Therapy (ASGCT)
The American Society of Gene and Cell Therapy (ASGCT) is the primary professional membership organization for gene and cell therapy. The Society’s members are scientists, physicians, patient advocates, and other professionals. The mission of the ASGCT is to advance knowledge, awareness, and education, leading to the discovery and clinical application of genetic and cellular therapies to alleviate human disease. For more information, please visit www.asgct.org.
About the JUST-AAV Platform Technology
JUST-AAV is a proprietary platform technology that utilizes modified adeno-associated virus (AAV) vectors. The technology entails insertion of miniaturized antibodies against receptors on selected tissues, organs or the blood-brain barrier onto the capsid surface, enhancing targeted delivery to those tissues and organs. Further capsid modifications minimize liver tropism and potentially mitigate hepatoxicity, which is a commonly observed safety concern. The name is derived from “JCR” “Ultimate destination of organ” “Safeguarding against off-target delivery” and “Transformative technology” reflecting its potential for broad application across various diseases.
About JCR Pharmaceuticals Co., Ltd.
JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceutical company that develops treatments that go beyond rare diseases to solve the world’s most complex healthcare challenges. We continue to build upon our 50-year legacy in Japan while expanding our global footprint into the U.S., Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, MPS II (Hunter syndrome), Fabry disease, acute graft-versus host disease, and renal anemia.
Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), MPS II, MPS IIIA and B (Sanfilippo syndrome type A and B), and more. Our core values – Putting people first, Forging our own path, Always advancing, and Committed to excellence – mean that the work we do benefits all our stakeholders, including partners, patients and employees. We strive to expand the possibilities for patients while accelerating medical advancement at a global level. For more information, please visit JCR’s global website: https://jcrpharm.com/.
