Promise for systemic amyloidosis (and beyond?)
Systemic amyloidosis is an uncommon disease in which abnormal cells (typically antibody-producing B cells) produce large amounts of protein that deposit as amyloid fibrils in various organs (heart, kidney, liver). These are the same kind of deposits that create plaque in the brain in Alzheimer’s disease. In systemic amyloidosis, the deposits cause organ damage, failure, and death and treatment options are limited. GSK is developing a monoclonal antibody directed at serum amyloid P (SAP), a naturally occurring glycoprotein that binds to amyloid fibrils. The attachment of the antibody to SAP which is bound to the fibrils then triggers an inflammatory response, bringing in immune cells that ingest and degrade the fibrils. To test this theory, 15 patients with amyloidosis received the antibody in a phase 1 study, and for most of those who received the higher doses, there were reductions in markers of amyloid fibril burden in the liver. Much more needs to be done to confirm the therapeutic relevance of this effect, but it is a promising start that has implication not only for systemic amyloidosis, but for the much more widespread disease of amyloid deposition that is Alzheimer’s. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component; Out, Out — Making Amyloid’s Candle Briefer (subscription access)
The complex world of Acute Myeloid Leukemia (AML)
Key takeaways of a review of AML: it mentions 13 important main types of gene mutations (which can occur individually or multiply, i.e. the combinatorics come to 213 = 8192 signatures) and lists approximately 50 drugs in clinical development for AML, most of which are targeted to specific molecular defects rather than generically cytotoxic. It is clear that soon, this is a disease(s) that will need to be managed through algorithms that will be too complex to reside in the head of a human oncologist: welcome Watson! Acute Myeloid Leukemia (subscription access)
Chimeric Antigen Receptor (CAR) T-cell therapy for multiple myeloma
The hottest thing in oncology in the CAR technique by which immune T killer cells are genetically reengineered to target a cancer marker and infused to destroy the tumor. Here, a group working with Novartis that has had past success in leukemia with CTL019 autologous cells (so-called because they target the CD19 cell marker, autologous because they are engineered from the patient’s own cells) reports the result of treatment of a patient with multiple myeloma (MM) who had failed no less than 9 prior lines of therapy. It worked – the patient has gone into durable remission at 12 months post treatment. The strange thing though is that most MM cells do not express CD19, in general, and this was confirmed with this patient in particular. So the fact that there was a remission leads one to ponder whether the small CD19 cell population could be an integral element of a “cancer community” without which the community collapses. Many in the past have highlighted the genetic heterogeneity of tumors – but this latest result may indicate that instead of being just a by-product of genetic instability, this diversity could be a sustaining element of some tumors. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma (subscription access)
Get rich with stem cells
A short Perspective highlighting an underworld that few of us are aware of: stem-cell tourism. FDA 361 regulation allows tissue harvested from a patient to be reused for the same patient (e.g. veins from the legs in a coronary artery bypass procedure). It seems that a number entrepreneurial physicians are performing liposuction and reinjecting stem cells (from the harvested fat tissues) in other diseased organs with the intention of improving health. Considering that there is no rigorous evidence that this works (or for that matter, that it does not), the likelihood of desperate patients getting fleeced is high, and the authors encourage the FDA to take action. A major loss here though is that because these clinics live in a netherworld, all this patient experience is not contributing to the overall understanding of what stem cells from fat could actually do for patients. Medicine’s Wild West — Unlicensed Stem-Cell Clinics in the United States (free access)
The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer a brief overview of highlights that might be of interest to our clients and others.