Tag: gene therapy

Recon takes an analytical look behind select developments in healthcare

An opinionated take on NEJM highlights for January-February 2021

Gene therapy in beta-thalassemia and sickle cell anemia Beta-thalassemia and sickle cell anemia are common genetic diseases of hemoglobin (Hb) which manifest themselves in the former through transfusion dependence, in the latter through painful vaso-occlusive crises that frequently land patients in the hospital in a pitiful state. BlueBird’s lentiglobin therapy is an ex-vivo gene therapy in which autologous stem cells are harvested, transfected with new HbA gene, and then returned to the patient. Because the HbA is slightly modified via a single amino-acid substitution (HbAT87Q), expression is trackable.  Now in

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Wrapping up 2021: An opinionated take on NEJM highlights for November-December 2021

In search of a diagnosis: deploying genomics at scale A substantial number of children have a disease identified as “rare” without having any kind of causative diagnosis (autism is not a causative diagnosis!). In a UK pilot study, 2,183 proband children were referred for exome sequencing with additional sequencing of family members if warranted. The overall diagnostic yield was surprisingly high, about 25% overall. Of the approximately half of probands who had neurological or sensory disorder, an explanatory diagnosis was reached in almost 40% of the cases. Two thoughts: 1)

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An opinionated take on NEJM highlights for July 2020

Stunting and the microbiome Stunting (low growth for age) affects > 20% of children across the globe and has major impact on the brain, on health, and on opportunities for success in life. The precise mechanism of stunting has remained elusive. Sanitation and diet diversity play a role but targeted interventions in these areas have had less impact than hoped for. Jeff Gordon from WashU has spent the last decade exploring the relationship between stunting and the microbiome, and now his group reports on a study that shows a clear

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Coronavirus and more: An opinionated take on NEJM highlights for January/February 2020

Keeping up with COVID-19 It’s not easy for a refereed weekly print periodical to keep up with an epidemic that evolves on a daily basis, but the NEJM is doing its best and all articles are free on-line. Most interesting beyond the description of the initial cluster in Wuhan are: (1) the first US case was quite severe and the patient received the antiviral remdesivir (was in development by Gilead for Ebola, but showing activity against coronaviruses) – it is now in testing in China; (2) the rigorous documentation of

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An opinionated take on NEJM highlights for April 2018

Are we nearing an asymptote with implantable cardiac pumps? Severe heart failure is common, and spare hearts for transplant are rare, which has led to the development of implantable mechanical alternatives. In the last few decades, progress has been immense, and in the latest installment of a 3rd (4th?) generation pump, outcomes have reached a level where survival of several years is the rule. Still, at every iteration incremental improvement is less, and performance remains well behind what happens with transplant in terms of complications such as infection, stroke, or

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A golden age for gene therapy: an opinionated take on NEJM highlights for December 2017

Successes in gene therapy for hemophilia B and A Hemophilia A and B are X-linked genetic diseases which prevents the formation of functional coagulant factors VII and IX respectively and cause a propensity to bleeding in about 20,000 people in just the US. The standard of care of intravenous administration of recombinant factors is effective but also burdensome, expensive, and does not fully prevent the disabling sequellae of the disease caused by repeated bleeding in the joints. A possible cure is to deliver a functional copy of the defective gene

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Gene therapy, headaches, and tattoos: an opinionated take on NEJM highlights for November 2017

Two new therapies against a horrible congenital disease – but trouble ahead on pricing… Spinal Muscular Atrophy (SMA) is a genetic disease that declares itself at a few months of age, and typically leads to death before the second birthday. Two studies for two different therapies are reported in the Journal. First, the final results for a phase 3 placebo-controlled trial studying nusinersen (Spinraza, Sarepta, approved by FDA Dec 2016) therapy which involves monthly injections into the infant’s spine of an RNA-based drug. These show a clear beneficial effect over

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Regeneration and mitigation: an opinionated take on NEJM highlights for March 2017

Gene therapy for sickle cell disease Typical diseases targeted by gene therapy are those for which there is a defect that prevents the production of a functional protein needed for normal life; remediation is achieved by inserting functioning copies of the gene, and fortunately, it is usually the case that expression at a low level is sufficient to greatly improve outcomes. The situation is different in sickle cell where the defective hemoglobin is actually harmful, and where success of gene therapy requires not only production normal hemoglobin, but replacement of

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