IL-1R2: A novel approach for gene therapy in atherosclerosis

Abstract Abstract 5 Background: Hemophilia B (HB), an X-linked bleeding disorder, is ideally suited for gene therapy. We investigated a novel approach using peripheral vein infusion of a single dose of a serotype-8 pseudotyped self-complementary adeno-associated virus (AAV) vector expressing a codon-optimized coagulation factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco). Methods: Six severe HB subjects (FIX ≤1%) were enrolled sequentially into one of three dose cohorts with two subjects in each group. Vector was administered without immunosuppression. The subjects were followed for 6–16 months post treatment. Results: AAV-mediated expression of FIX at 2–11% of normal was observed in all subjects. Four of the six have discontinued prophylaxis and remain free of spontaneous hemorrhage. The other two have increased the interval between FIX prophylaxes. A high-dose subject developed asymptomatic, transient elevation of serum transaminases associated with detection of AAV8 capsid specific T cells in peripheral blood. The second high-dose subject experienced a slight increase of liver enzymes, of less clear etiology. Treatment of each with a short course of steroids led to rapid normalization of the transaminases and maintenance of FIX levels in the 3–11% range. Conclusion: Peripheral vein administration of scAAV2/8-LP1-hFIXco was well tolerated and resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype. Immune-mediated clearance of AAV-transduced hepatocytes remains a concern but our data suggest that this process may be controlled with a short course of steroids without loss of transgene expression. Hence, our novel approach shows promise for gene therapy of HB and other protein deficiencies. (ClinicalTrials.gov number, NCT00979238) Disclosures: Nathwani: Amsterdam Molecular Therapeutics: Patents & Royalties. Gray:Amsterdam Molecular Therapeutics: Patents & Royalties. Davidoff:Amsterdam Molecular Therapeutics: Patents & Royalties.

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687. “Same Day” Ex Vivo Regional Gene Therapy: A Novel Approach To Enhance Bone Repair

Molecular Therapy ◽

10.1016/s1525-0016(16)38128-x ◽

2010 ◽

Vol 18 ◽

pp. S268

Keyword(s):

Gene Therapy ◽

Bone Repair ◽

Ex Vivo ◽

Novel Approach ◽

Regional Gene

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W1340 A Novel Approach for Gene Therapy in IBD

Gastroenterology ◽

10.1016/s0016-5085(10)63231-3 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-703

Author(s):

Hamed Laroui ◽

Guillaume Dalmasso ◽

Hang Thi Thu Nguyen ◽

Yutao Yan ◽

Shanthi V. Sitaraman ◽

...

Keyword(s):

Gene Therapy ◽

Novel Approach

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GENE THERAPY: A NOVEL APPROACH TO TREATMENT OF THE DEGENERATION OF INTERVERTEBRAL DISCS

Journal of Musculoskeletal Research ◽

10.1142/s0218957702000897 ◽

2002 ◽

Vol 06 (03n04) ◽

pp. 181-187 ◽

Cited By ~ 1

Author(s):

Jiangwei Tan ◽

Yougu Hu

Keyword(s):

Gene Therapy ◽

Back Pain ◽

Disc Degeneration ◽

Deep Understanding ◽

Intervertebral Discs ◽

Research Field ◽

Clinical Approach ◽

Novel Approach ◽

Physiology And Biochemistry ◽

Lowback Pain

The degeneration of intervertebral discs is one of the pathophysiological causes of lowback pain which has been seriously disturbing human health at the present, No clinical approach can provide prophylaxis or treatment for disc degeneration. But people are now thinking about gene transfer for the prevention of disc degeneration to reduce the incidence of back pain. This idea originated from the development of molecular biology; the deep understanding of the physiology and biochemistry of the intervertebral discs, and the growing scope of gene therapy. The increasing publications on gene therapy for disc degeneration have shown us the future of this research field, and revealed possible difficulties in the process of the study. This article focuses on several important aspects of gene therapy for disc degeneration.

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