Biomedical subjects

Nick Giannoukakis

Publications and source records attributed to Nick Giannoukakis.

22 records · Page 2Linked to original sources

PubMed2002

Gene therapy strategies to prevent autoimmune disorders.

Autoimmunity accounts for a significant percentage of human disease and remains a challenging syndrome to treat. While systemic immunosuppression can be beneficial, the associated toxicity of the pharmacologic agents necessitates an antigen-specific approach to silence, eradicate or prevent the genesis of autoreactive immune cells. Gene therapy offers the possibility of providing precise antigen-targeted therapies, thereby sparing the patient the significant toxicity associated with lifelong commitment to chemical immunosuppressives. Gene-based therapies could include, but are not limited to the manipulation of immune networks of tolerance by antigen presenting cell engineering, pro-inflammatory cytokine blockade using soluble antagonists expressed from viral vectors as well as modulation of immune regulatory networks. The potential utility of gene therapy strategies promoting tolerance in two model autoimmune disorders, type I diabetes mellitus and rheumatoid arthritis are discussed in this review.

Arthritis, Rheumatoid↗

PubMed2002

Genes and engineered cells as drugs for type I and type II diabetes mellitus therapy and prevention.

Despite the manageability of diabetes mellitus, complications associated with the disorder necessitate novel approaches to prevent immune-mediated impairment and destruction in type 1 diabetes, as well as the pancreatic insufficiency and peripheral resistance to insulin in type 2 diabetes. Islet transplantation is evolving into a clinical reality to treat type 1 diabetics and novel uses of gene engineering technology promise to result in tolerance to auto-, allo- and xenoantigens as well as microenvironment-specific immunosuppression. Through the use of a variety of gene delivery vehides, an increasing number of studies demonstrate the feasibility of shielding islet transplants and surrogate beta cells from immune rejection by the local secretion of immunosuppressive soluble molecules and anti-apoptotic factors. Although the achievements of gene and cell therapy in type 2 diabetes mellitus are less clear, seminal studies demonstrate the relevance of this approach to the treatment and perhaps prevention of the underlying causes of the disease, including obesity and insulin resistance. In this review, we attempt to illustrate pivotal studies demonstrating the suitability of genes and cells as drugs in type 1 and type 2 diabetes mellitus, and also provide some other targets that may be suitable for clinical utility.

Animals↗

PubMed2002

NBI-6024 (Neurocrine Biosciences).

Neurocrine is developing NBI-6024 in collaboration with Taisho, as part of Neurocrine's altered peptide ligand (APL) program, as a potential treatment for type I diabetes. By July 2002, Neurocrine had completed four phase I/II trials of NBI-6024 and the compound was in phase IIb studies in Europe and phase Ib studies in the US. By October 2002, a second phase IIb trial was scheduled to begin in the US later in 2002 or in early 2003.

Journal Article↗

PubMedDate not supplied

Gene therapy for type 1 diabetes.

The most intensively studied autoimmune disorder, type 1 diabetes mellitus (DM1), has attracted perhaps the greatest interest for gene-based therapeutic and prophylactic interventions. The final clinical manifestation of this immunologically and genetically complex disease, the absence of insulin, is the major starting point for almost all the gene therapy modalities attempted to date. Insulin replacement by transplantation of islets of Langerhans or surrogate beta cells is the obvious choice, but the allogeneic nature of the transplants activates potent antidonor immunoreactivity necessitating gene and cell-based immunosuppressive strategies as an alternative to the toxic pharmacologic immunosuppressives indicated for classic solid organ transplants. Accumulating knowledge of the cellular mechanisms involved in onset, however, have yielded promising tolerance induction prophylactic approaches using genes and cells. Despite the early successes in a number of animal models, the true test of efficacy in humans remains to be demonstrated.

Animals↗