Category: NEJM Highlights

Hitting reset for the immune system Every time I get into a new issue of the NEJM, I have a sense of anticipation as in “will this one have an article that blows my mind?” It doesn’t happen very often, perhaps once or twice a year, but when it does, it’s an awesome feeling. From Germany, an application of CAR-T (CD19 directed) therapy to severe autoimmune disease reporting on 15 patients, 8 with severe SLE with renal involvement, 3 with myositis, and 4 with scleroderma, all progressing despite treatments with

A step forward for kidney xenotransplantation A report on the recent, well-publicized, temporary transplantation of kidneys from genetically modified pigs in two deceased individuals at NYU. The kidneys functioned well and there was no sign of acute rejection, but because these experiments took place over only 54 hours, this is not indicative of longer term compatibility of the transplant of kidneys from this particular strain of pigs. A question in my mind is why there have not been kidney xenotransplants in live patients yet – especially given a recent porcine

What makes an indication especially tough? The combination of a lack of understanding about the mechanism of disease and a lack of clarity on what endpoints would be sufficient for approval of a therapy in studies of reasonable duration. This month, two good examples in the NEJM.   A phase 2b success in NASH Non-alcoholic steatohepatitis (NASH) is a common slow-progressing disease and for most affected individuals the timescale to liver-related morbidity is at least 20 years, although some progress much faster. NASH is also a graveyard of clinical programs

The weird world of synthetic biology In biology 101, one learns about the alphabet that translates DNA/RNA code into amino acids sequences ultimately resulting in proteins. Given that there are 64 possible triplet codons and 20 amino acids, multiple codons can map to the same amino acids. But this mapping can be reassigned including incorporating new amino acids – it has been done in E. coli with the promise of generating biologics with novel properties, although applications are not yet clear. A more practical application is to create strains of

A new approach to schizophrenia Antipsychotic agents treat schizophrenia by manipulating the dopaminergic system. While they are effective at treating psychosis, they can have major side effects and they lack the ability to address so called negative symptoms e.g. apathy, lack of social connection, poverty of thought.  Enter the muscarinic cholinergic system which is tricky to manipulate in the CNS without untoward systemic effects as Lilly found out with their M1/4 agonist xanomeline.  Karuna Therapeutics has now licensed the molecule and cleverly combined with it with trospium, an antagonist with