Sunday, October 23, 2016

CBS Sunday Morning on 23 October 2016: treating genetic based diseases

Martha Teichner did the cover story Fighting genetic disease with help from HIV virus, which highlighted the work of Dr. Alessandra Biffi, who is now the leader of the gene therapy program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The big take home message of the piece: "So far, not a single gene replacement therapy has been approved by the FDA."

Other stories Jim Axelrod on Phil Collins, receding glaciers at Glacier National Park in Montana, Lee Cowan on the "Seven Magic Mountains" off I-15 near Las Vegas, Anthony Mason on lawyer John Gresham, Mo Rocca on Maureen Dowd.

Almanac was the first plastic surgery on October 23, 1814.

There was a "buzzword" feature on the word "pivot."

Moment of nature was on the White Mountain National Forest in New Hampshire.

"Seven Magic Mountains" was created by Ugo Rondinone. It is about 10 miles south of Las Vegas, near Jean Dry Lake. Earlier, near Jean Dry Lake, there was "Rift," the first of a 530-mile-long series of sculptures Michael Heizer dubbed "Nine Nevada Depressions." Related to "Sunday Morning's" previous discussion of bumper stickers, Magic Mountain uses Day-Glo colors [The Day-Glo colors — brilliant pinks, deep blues and bright greens, eye-searing yellow-orange, Silver State silver, black and white — from review-journal]

Of gene therapy, a paper by Kaufmann et al. [ EMBO Mol Med. 2013 Nov; 5(11): 1642–1661 ] notes

China was the first country to introduce a gene based-drug (Gendicine®), into the market in 2004. Gendicine is an adenovirus-p53 based gene therapeutic approved for the treatment of patients with head and neck squamous cell carcinoma (Wilson, 2005). With more than 10,000 treated patients no overt adverse side effects have been reported for Gendicine®. However, the therapeutic efficacy of this drug is still controversial (Sheridan, 2011; Shi & Zheng, 2009). In Europe, alipogene tiparvovec (also known as Glybera®) was approved for the treatment of familial lipoprotein lipase deficiency (LPLD) at the end of 2012, and thus, was the first commercially available gene therapeutic product in the Western world (Büning, 2013; Miller, 2012; Ylä-Herttuala, 2012). The marketing authorization for Glybera® clearly represents a milestone in the development of gene therapy as an accessible therapeutic option for LPLD patients. The Glybera® example also revealed the multiple layers of complexity that have to be solved before a drug-based product reaches the market. In addition to patent issues, the costs for adequate production of the advanced therapy medicinal product (ATMP) according to good-manufacturing practice (GMP) requirements are enormous. Moreover, costly and extensive pharmacology and toxicology studies have to be conducted in the absence of clearly defined standards, even in cases where very similar vector backbones are used. In addition, the review process and eventual authorization by the respective agencies adds another layer of complexity as exemplified by the hurdles encountered during the review process for Glybera® (as reviewed elsewhere (Bryant et al, 2013)). Thus, there are still multiple issues to be addressed in gene therapy before gene-based products enter routine clinical application to provide safe and affordable therapeutic drugs for otherwise non-treatable overt and chronic diseases.

Kaufmann cites a paper by Biffi: Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341:1233158

In passing, a claim from US Patent 8957044 , related to gene-based therapy:

A method of treating a an X-linked myotubular myopathy (XLMTM) in a mammal in need thereof, the method comprising systemically administering to the mammal a composition that increases expression of myotubularin in a muscle of mammal, wherein the composition comprises an adeno-associated viral (AAV) vector comprising a nucleic acid sequence encoding the myotubularin gene (MTM 1) operably linked to a muscle specific promoter, further wherein the function of the diaphragm of the mammal is improved, as compared to the diaphragm of the mammal in the absence of administration of the composition, wherein strength is increased in the muscle.


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