Metabolic Disorder – VJRegenMed

Treating Krabbe disease with FBX-101

Simon Ng — Thu, 17 Feb 2022 12:04:56 +0000

Krabbe disease is a rare genetic disorder caused by a deficiency of the enzyme galactocerebrosidase (GALC) and can result in mortality in infants. John Maslowski, CCO, Forge Biologics, Columbus, OH, provides a brief overview of FBX-101, an adeno-associated virus (AAV)-based gene therapy for patients with Krabbe disease. The therapy is currently being assessed in the Phase I/II RESKUE trial (NCT04693598), where patients also receive a bone marrow transplant. FBX-101 has demonstrated preliminary efficacy and the trial will additionally assess safety as well as mobility in patients. This interview took place at Advanced Therapies Week 2022.

LYS-GM101 AAV gene therapy for GM1 gangliosidosis

admin_vjr_user — Thu, 23 Dec 2021 16:24:52 +0000

GM1 gangliosidosis is a rare autosomal lysosomal storage disorder caused by mutations in the GLB1 gene which encodes β-galactosidase (Beta-gal), resulting in toxic accumulation of GM1 ganglioside predominantly in the central nervous system (CNS). Michael Hocquemiller, PhD, Lysogene, Paris, France, describes ongoing research into LYS-GM101, an adeno-associated virus serotype rh.10 (AAVrh.10) vector carrying GLB1 cDNA, administered via a single injection into the cisterna magna. Following promising results obtained in pre-clinical studies in mouse, cat and non-human primate disease models, an open-label two-stage adaptive design study (NCT04273269) is currently underway which will evaluate the safety and efficacy of LYS-GM101 in patients with GM1 gangliosidosis. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

GNT0003: AAV gene therapy for Crigler-Najjar syndrome

admin_vjr_user — Thu, 23 Dec 2021 16:24:51 +0000

Lorenzo D’Antiga, MD, Hospital Papa Giovanni XXIII, Bergamo, Italy, describes the Phase I/II CareCN (NCT03466463) clinical trial evaluating GNT0003 therapy, an adeno-associated virus vector serotype 8 (AAV8) encoding hepatic UGT1A1, in patients with Crigler-Najjar syndrome (CN). In this dose-escalation study, no GNT0003-related serious adverse events were reported in the five patients treated. In patients treated with a higher dose, GNT0003 was demonstrated to be safe and restored UGT1A1 expression to levels allowing safe phototherapy withdrawal. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

The safety of AVR-RD-01 gene therapy for Fabry disease

admin_vjr_user — Wed, 22 Dec 2021 18:29:34 +0000

Mark Thomas, MD, Royal Perth Hospital, Perth, Australia, provides an update on the ongoing combined Phase I and II FAB-GT clinical trials (NCT03454893) of AVR-RD-01, an investigational ex vivo lentiviral gene therapy for Fabry disease (FD). In these studies, two conditioning agents, low-dose melphalan or busulfan, were used. Interim safety data from five patients with FD receiving enzyme replacement therapy (ERT) the Phase I study and eight treatment-naïve patients in the Phase II study indicates a favorable safety profile for AVR-RD-01, with no adverse events, serious adverse events or allergy development related to the investigational product reported to date. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

The unmet medical need for Crigler-Najjar syndrome

admin_vjr_user — Wed, 22 Dec 2021 18:29:32 +0000

Lorenzo D’Antiga, MD, Hospital Papa Giovanni XXIII, Bergamo, Italy, describes Crigler-Najjar syndrome (CN), an inherited liver metabolism disorder cause by a lack of hepatic uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1), which results in severe unconjugated hyperbilirubinemia that can cause irreversible neurological injury and death. The current standard-of-care is daily phototherapy, however this treatment becomes less effective with increasing age, making liver transplantation ultimately necessary. This has prompted the investigation of gene therapy approaches with the aim of finding novel, less invasive curative strategies for CN. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

LYS-SAF302 AAV gene therapy for MPS IIIA

admin_vjr_user — Wed, 22 Dec 2021 18:29:28 +0000

Michael Hocquemiller, PhD, Lysogene, Paris, France, provides an overview of the ongoing Phase II/III AAVance (NCT03612869) study of LYS-SAF302 in patients with Mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo type A. LYS-SAF302 is an adeno-associated virus serotype rh.10 (AAVrh.10) vector carrying functional human N-sulfoglucosamine sulfohydrolase (SGSH) cDNA. This study aims to evaluate the efficacy in improving the neurodevelopmental state of MPS IIIA patients following one-time intracerebral administration of LYS-SAF302. Cerebrospinal fluid biomarker data obtained at one-year follow up supports the biological activity and therapeutic potential of LYS-SAF302. This interview took place at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021.

Overcoming immunogenicity of gene therapies

Simon Ng — Mon, 06 Dec 2021 09:29:02 +0000

Timothy Miller, PhD, Forge Biologics, Columbus, OH, discusses the impact of pre-existing immunogenicity against adeno-associated virus (AAV)-based gene therapies. Patients who have an immune response to recombinant AAV vectors will require immunosuppression to benefit from gene therapies. Various strategies can be employed to overcome this issue by utilizing combination therapies, especially in the case of FBX-101, an AAV-based gene therapy for patients with Krabbe disease. This interview took place at Meeting on the Mesa 2021.

RESKUE: AAV-based gene therapy for Krabbe disease

Simon Ng — Mon, 06 Dec 2021 09:29:01 +0000

Timothy Miller, PhD, Forge Biologics, Columbus, OH, describes the trial design of the Phase I/II RESKUE trial (NCT04693598), assessing FBX-101, an adeno-associated virus (AAV)-based gene therapy for patients with Krabbe disease receiving a bone marrow transplant. The preliminary results of the dose escalation trial will aim to be released by 2022. This interview took place at Meeting on the Mesa 2021.

Treating Krabbe disease with AAV-based gene therapies

Simon Ng — Mon, 06 Dec 2021 09:28:59 +0000

Timothy Miller, PhD, Forge Biologics, Columbus, OH, provides an overview of the current treatment landscape for Krabbe disease and the potential for gene therapy as a curative treatment. Krabbe disease is a lysosomal storage disorder that affects the nervous system, and the current standard of care is a bone marrow transplant. Dr Miller additionally describes an adeno-associated virus (AAV)-based gene therapy that when administered in conjunction with the bone marrow transplant, lacks the immunogenicity-related issues associated with AAV vectors. This interview took place at Meeting on the Mesa 2021.

The role of regenerative medicine in treating diabetes

Simon Ng — Tue, 30 Nov 2021 18:07:22 +0000

Lorenzo Piemonti, MD, Università Vita-Salute San Raffaele, Milan, Italy, discusses the importance of advanced therapies in treating Type 1 diabetes. Cell therapies have the potential to reverse the loss of insulin-producing β cells and Prof. Piemonti highlights the advantages of utilizing regenerative medicine in the field. The efficacy of treatments can be effectively measured with well-established biomarkers, and β cells are not required to be in a specific part of the body to be producing insulin. Islet transplantation has additionally proven that cell therapies is a viable treatment for diabetes. This interview took place at the 6th World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021).