Lysosomal Storage Disorders – VJRegenMed

Novel gene therapies for metachromatic leukodystrophy

Simon Ng — Thu, 03 Mar 2022 17:46:25 +0000

Kent Christopherson, PhD, Orchard Therapeutics, Boston, MA, describes the development and mechanism of action of atidarsagene autotemcel, a gene therapy consisting of an autologous CD34⁺ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced using a lentiviral vector. The gene therapy, which has been approved in the EU, aims to treat metachromatic leukodystrophy (MLD) and the vector encodes the human arylsulfatase-A (ARSA) gene, which is faulty in patients with MLD. HSPC cells with the functional gene can subsequently produce the correct protein, which can be trafficked and permanently integrated in the central nervous system (CNS). This interview took place at Advanced Therapies Week 2022.

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.

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.

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.

Neuraminidase could improve AAV9 gene therapy for Batten disease

admin_vjr_user — Thu, 12 Aug 2021 10:07:41 +0000

Kathrin Meyer, PhD, Nationwide Children’s Hospital, Columbus, OH, discusses the administration of neuraminidase prior to or in combination with AAV9 gene therapy in Batten disease, a neurological condition that can lead to macular degeneration. In a mouse model, intravitreal administration of neuraminidase resulted in enhanced delivery of AVV9 into the eye by removing certain sugar residues on entry receptors, improving penetration of the virus into deeper structures of the eye. While additional research is required to assess safety in larger models, neuraminidase pretreatment holds potential in a range of neurological conditions affecting the eye, particularly when targeting the inner nuclear layer. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

AVR-RD-01: ex vivo lentiviral gene therapy for Fabry disease

admin_vjr_user — Fri, 14 May 2021 14:11:25 +0000

Mark Thomas, MD, Royal Perth Hospital, Perth, Australia, provides an overview of the current treatment landscape for Fabry disease and the rationale behind the application of gene therapy technologies and their potential to offer a one-time curative therapy for Fabry disease. He describes updated results from the ongoing Phase I and II FAB-GT clinical trials (NCT03454893) of AVR-RD-01, the first investigational ex vivo lentiviral gene therapy for Fabry disease. The results presented at ASGCT 2021 indicate sustained enzyme activity and a 100% globotriaosylceramide (Gb3) kidney clearance at one-year in the most recent Phase II study patient. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.