A few days ago we wrote about the role of rare earth metals in imaging and early research into treatment options for DIPG, a rare and deadly form of brain cancer. We interviewed Dr. Russell Lonser of the NIH to better understand his research in Convection Enhanced Delivery (CED) whereby drugs are delivered directly to tumors or other hard to reach places, in the case of other diseases. In addition to CED, rare earth metals play a key role in many areas of medical research. We will attempt to cover some of these areas in future posts.
CED appears to be an extremely complicated process of both identifying in the case of DIPG, specific tumor areas, (DIPG has been described as a tumor which resembles sand in a bed of grass) and then effectively and accurately delivering drugs to that area. We asked Dr. Lonser why the focus on CED and not intravenous drug delivery. He told us that the blood-brain barrier is unique to the central nervous system, if you give a drug into the mouth or vein or artery, the drug will get to where it needs to go. But vessels in the central nervous system work a bit differently. Only very small molecules can successfully cross over the barrier. This is why chemotherapy doesn’t cross into these types of tumors very well. The idea behind CED is to bypass the blood brain barrier.
Gadolinium and gadolinium compounds are commonly used in medical imaging and are a critical component to CED. We spoke with Daniel Sodickson, Vice Chair for Research at the Department of Radiology at NYU about gadolinium and its role in medical imaging. Basically, gadolinium works remarkably well as a contrast agent because it has a very distinctive magnetic field. Gadolinium changes the rate of the decay of the signal (it typically makes it decay faster). This means the signal in the region is clearer, enabling better views of tumors, according to Sodickson.
Dr. Lonser’s focus remains on the drug delivery methodology, mainly because the application of CED could be used for other currently non-treatable diseases such as Parkinson’s and other metabolic disorders. He has completed preliminary research on two patients, one with DIPG and the other with a different metabolic disorder. We asked Dr. Lonser about the results of his study particularly because the one DIPG patient still died within 4 months after infusion. We asked Dr. Lonser if the study results suggested that the drug itself needed to be modified or if there was a problem with the delivery method. He explained, Both the drug will have to be effective and safe and the delivery technology and methodology will have to effectively deliver drugs correctly. This has been used with malignant gliomas for adults. For children, we are at the very early stages.
The research in terms of drug delivery to the brains of adults is a bit further along the path though there has not been a significant increase in survival compared to the control group. According to Dr. Lonser, infusions weren’t done with imaging tracking, it’s essentially a big black box around distribution.
Because we are really at the front edge of understanding this, unfortunately, more questions than answers remain. How much of the brainstem needs to be treated? Do we need to treat multiple times? Do we need to treat other non-tumor areas? These are some of the things that will emerge from the research. Dr. Lonser’s study is currently waiting an IND (Investigation of a New Drug) approval from the FDA to do the trial, which he hopes will come soon. Results will be made available in one year.
We will cover gadolinium in greater detail, in another post.