Rare Diseases – VJRegenMed

Overcoming manufacturing issues in gene therapies for rare diseases

Simon Ng — Wed, 20 Apr 2022 16:45:46 +0000

John Maslowski, CCO, Forge Biologics, Columbus, OH, discusses strategies to optimize the manufacturing of gene therapies for rare diseases. In addition to regulatory barriers, maintaining the consistency of the product is vital, especially when manufacturing occurs in large-scale bioreactors. To ensure the cost of production remains low and the patients’ needs are successfully met, he emphasizes the need to use automated analytical tools in a closed system. Assessing product quality via high throughput systems can expedite production times on a larger scale. This interview took place at Advanced Therapies Week 2022.

Innovations in treating rare diseases with gene therapies

Simon Ng — Wed, 20 Apr 2022 16:45:46 +0000

John Maslowski, CCO, Forge Biologics, Columbus, OH, comments on the current treatment landscape for rare diseases, especially in the field of gene therapies. With a large number of rare diseases lacking any form of treatment, finding curative solutions for these rare diseases remain an unmet need. Finding a suitable clinical model is essential to develop treatments, especially when the natural history group in a clinical trial is preferable to placebo groups, as in the case of studies targeting Krabbe disease. Introducing closed automated systems in the manufacturing process will additionally enable the production of gene therapies in an economical manner. This interview took place at Advanced Therapies Week 2022.

Applications of single-cell multi-omics analysis

Simon Ng — Thu, 25 Nov 2021 14:55:39 +0000

Yan Zhang, PhD, Mission Bio, San Francisco, CA, describes the capabilities of the Tapestri Platform, which utilizes single-cell multi-omics technology. Tapestri can accurately measure the efficacy and safety of cell and gene therapies by monitoring genomic and protein changes at a single-cell level. The platform can additionally elucidate mechanisms of relapse or resistance to cancer therapies. Resistance can occur due to mutations or changes in the tumor microenvironment, and the platform enables analysis of resistant cells to gain insight into disease progression. This interview took place at Meeting on the Mesa 2021.

Expanding the repertoire of CRISPR-based genomic editors

Simon Ng — Thu, 04 Nov 2021 18:04:42 +0000

Devyn Smith, PhD, Arbor Biotechnologies, Cambridge, MA, provides a brief overview of the tailored nuclease therapies developed at Arbor Biotechnologies. Multiple nucleases have been discovered that are superior to the original Cas9 endonuclease and a portfolio of nucleases, which have been modified to improve efficacy, has been developed. Certain nucleases can be adapted for specific diseases such as Huntington’s disease, a trinucleotide repeat disorder, by having the optimal protospacer adjacent motif (PAM). This interview took place at Meeting on the Mesa 2021.

Tailored nucleases for primary hyperoxaluria

Simon Ng — Thu, 04 Nov 2021 18:04:40 +0000

Devyn Smith, PhD, Arbor Biotechnologies, Cambridge, MA, discusses utilizing tailored nuclease-based CRISPR therapies to treat primary hyperoxaluria, a genetic condition that leads to the accumulation of oxalate in the liver and subsequent end-stage renal disease in children. Current treatments have a mixed efficacy and new genetic therapies aim to treat primary hyperoxaluria by multiplex gene knockout, where the nuclease targets two known protein targets. This interview took place at Meeting on the Mesa 2021.

Combining rAAV gene therapy with standard-of-care for the treatment of citrullinemia

admin_vjr_user — Wed, 18 Aug 2021 16:32:46 +0000

Gloria Gonzalez-Aseguinolaza, PhD, Universidad de Navarra, Pamplona, Spain & Vivet Therapeutics, Paris, France, discusses ongoing research into gene therapies for citrullinemia type I (CTLN1) in pediatric patients, a rare autosomal recessive genetic disorder caused by mutations in the ASS1 gene, that can result in early-onset hyperammonemia crisis. Combining standard of care nitrogen scavenger therapy with arginine administration prior to administration of VTX-804 gene therapy, a recombinant adeno-associated virus (rAAV) vector expressing the human ASS1 enzyme, has been demonstrated to control initial disease symptoms and improve therapeutic efficacy in a mouse model. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

HSC gene editing highlights from ASGCT 2021

admin_vjr_user — Wed, 18 Aug 2021 16:32:42 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, discusses her highlights from the American Society for Cell & Gene Therapy (ASGCT) Annual Meeting 2021. Exciting advances in gene editing technology include the development of CRISPR-associated transposase systems and prime editing, which can overcome toxicities associated with double-strand breaks in hematopoietic stem cells. In vivo genome editing is another promising area of research, despite safety and efficacy challenges that still need to be addressed before this technology can be used in the clinic. Dr Vavassori also highlights ongoing research into the potential of adverse events and toxicity caused by genome editing, including chromothripsis and translocations, as gene therapies approach clinical approval. This interview took place during the ASGCT 24th Annual Meeting 2021.

Cardiosphere-derived cells in myocardial regeneration

admin_vjr_user — Fri, 13 Aug 2021 12:05:07 +0000

Linda Marban, PhD, Capricor Therapeutics, Beverly Hills, CA, introduces CAP-1002, an allogeneic cardiosphere-derived cell (CDC) therapy that promotes the regeneration of cardiac muscle by stimulating the release of exosomes, thus inducing endogenous repair mechanisms, a reduction in inflammation and ultimately, muscle tissue generation. Clinical trial data indicates that CAP-1002 therapy can result in significant improvements in cardiac and skeletal muscle in patients with Duchenne muscular dystrophy (DMD). CDC-derived extracellular vesicles (EVs) are also being investigated as a therapeutic given their tropism to cardiac and skeletal muscle and ease of storage and delivery. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

CRISPR-Cas9 gene-edited HSPCs for Friedreich’s ataxia

admin_vjr_user — Fri, 13 Aug 2021 12:05:06 +0000

Stephanie Cherqui, PhD, University of California, San Diego, La Jolla, CA, describes a CRISPR-Cas9 gene-edited hematopoietic stem and progenitor cell (HSPC)-based therapy for Friedreich’s ataxia (FRDA), a rare mitochondrial neurodegenerative disorder. The transplantation of wild-type HSPCs into an FRDA mouse model led to the successful prevention of neurodegeneration in the dorsal root ganglia. Given that FRDA is predominantly caused by a GAA repeat expansion mutation within the frataxin gene (FXN), CRISPR-Cas 9 technology was used to excise the GAA expansion mutation from patient-derived HSPCs, resulting in the restoration of frataxin expression. Future research aims to evaluate the clinical potential of this autologous therapy for FRDA. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 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.