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Month: October 2024

Dear Dr. K; 

Dear Dr. K; 

I heard on the news that there is a new nasal EpiPen, can it really work for anaphylaxis? 

The short, simple and sweet answer is “yes”.  But if you’ve read this newsletter previously you know how I like to elaborate on simple answers.    

The FDA did recently approve “Neffy” a single dose nasal spray containing epinephrine.  It can be used in adults and children who weigh 66 pounds or more.  There is a pediatric spray for smaller children that is also undergoing clinical trials.   

In addition to being “needle free” some additional advantages over the injectable forms (EpiPen and AuviQ) are its compact size, heat stability and ease of use.   

As you may know the mucus membranes in the mouth and nose provide a medium for almost instant absorption of medicines and recreational drugs.  Speaking of recreational drugs, far too many Americans die from opioid overdose.  In this regard the nasal spray Narcan has saved many lives.  Narcan (naloxone) is an opioid antagonist, and the spray is immediately absorbed and can prevent death from an overdose.   

In terms of medications Calcitonin nasal spray is an option for treating loss of bone density (osteopenia/osteoporosis).  It is a salmon derived bone building hormone that is absorbed intact through the nasal membrane.  If it were swallowed its breakdown in stomach would render it useless.   

Two commonly used “instant onset medications” that are absorbed in the mouth are nitroglycerine for angina/heart attacks and ondansetron for relief of nausea/vomiting.    

Currently 33 million Americans have a prescription for injectable epinephrine with this many people at potential risk for anaphylaxis it is not difficult to appreciate that unfortunately there have been some deaths due to fear of injection or due to inadvertent mishap while trying to inject the medicine.  The simple single dose nasal spray should prevent these issues.   

Because of its ease of use and safety it is also being studied for possible use to treat acute severe hives and acute severe asthma.  But the jury is still out in these applications.  However, if it is approved for these situations keep in mind that it is an urgent stop-gap, and as is true with its anaphylaxis application, immediate urgent care is still necessary.   

Protein Degraders 

Protein Degraders 

Inflammation is the causative common denominator for most of the allergic and autoimmune conditions that plague humans.  Inflammation is mediated at a cellular level by inflammatory proteins.  Many current therapies work by inhibiting the function of inflammatory proteins.  But a new evolving strategy is to develop protein degraders to remove these inflammatory proteins completely. 

Targeted protein degradation is a process using a new class of medicines that may revolutionize the treatment of inflammatory diseases.  These medicines are designed to selectively target and promote the degradation of disease-associated proteins.  By ramping up the body’s natural protein disposal system targeted protein degradation can remove the pathological proteins that are causing cellular inflammation.   

All of our human cells have a garbage disposal system for removing unwanted or senescent proteins.  It is a good system but of limited capacity.  When cells are overwhelmed with a myriad of inflammatory proteins the disposal system simply can’t keep up, think sanitation strike scenario.  The system works in large part by tagging unwanted proteins with a molecule called ubiquitin.  (In my adopted home state of Alabama, we’d pronounce that as “you-be-quitin”  as in “you’re out of here”).   

So, protein degrader medicines work by dramatically enhancing the ubiquitin targeting process, thus speeding removal.  Keep in mind it is only the unwanted proteins that are specifically targeted.  One benefit of this approach over protein inhibitors is the complete removal of the bad proteins, not just inhibiting them.  In the latter case a log-jam can occur where there is such a large buildup of the bad proteins not all of them can be inhibited and hence inflammation continues.  Another benefit of degraders over inhibitors is that inhibitors can also block important cellular processes thereby suppressing desirable immune function (i.e. they can suppress the immune system leading to a greater chance for infections).   

Early research trials with a degrader IRAK4 have shown it to be effective in treating two skin diseases:  atopic dermatitis and hidradenitis suppurativa (a chronic condition of boils/cysts in the armpits).  As in all new research there is a lot more study to be done, but the outlook is very promising.   

Lucky 13 

Lucky 13 

13% of Americans have not been infected with Covid-19.  Roughly the same number is true in other developed countries where epidemiologic studies have been done.  Is it simply good luck or is some other force at work?   

As it turns out a recent bit of research published in the journal Nature points toward genetics.  Scientists in the UK placed infecting doses of Corona virus in the nostrils of study volunteers.  The small minority who did not become ill had high levels of gene HLA-DQAZ a gene that controls the production of interferon (an immune protein that does what the name implies:  interferes with viral replication).  The study participants who became ill produced modest amounts of interferon, but not enough to stop the virus from reaching the critical mass necessary to cause infection.  

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL is a recently FDA approved therapy for treating certain types of metastatic cancer.  It has been referred to as a “living drug” as it is made up of the individual patients T lymphocytes.  It does so by taking cancer-targeting T cells from the patient’s own tumor and then growing them into billions more of the same cells in the lab and then re-infusing them into the patient.   This massive influx of warrior T cells can destroy the tumor whereas the previous small number of T cells were just holding it at bay.  

The initial FDA approval is for metastatic melanoma but it’s used for other solid tumors such as breast, pancreas and colon cancers.   

TIL is not the first use of immune cells to fight cancer.  CAR T-Cell therapy is another FDA approved method to fight certain “liquid” cancers, primarily leukemia, lymphoma, and multiple myeloma.  So far it has not proven effective for solid cancers.  CAR T-Cell therapy is so named because it involves making a chimeric antigen receptor (CAR) on T-cells.  It uses genetic engineering to modify the patient’s own T-cells so they can recognize (and then destroy) a specific cancer cell signal (antigen).  CAR-T therapy has helped and cured thousands of patients but one drawback of its use is that it is tricky to find a molecular signal (antigen) that is totally unique to the cancer.  Since healthy cells may also share this molecular signal, they can sometimes be damaged by the chimeric T-cells.  TIL on the other hand doesn’t modify the innate targeting system of the T-cells it simply uses a normal immune cytokine IL-2 (interleukin-2) to boost cell growth.  As it turns out one “target” that the TIL cells seem to pick out is the mutated protein that would otherwise control healthy cell growth.  Once this protein undergoes a Jekyll-Hyde transformation it allows uncontrolled cell growth otherwise known as cancer.