Here’s something that may seem too good to be true, and in my opinion, it is.  I’m writing about it as a cautionary measure.

Researchers at Guangzhou University, China have published a case report of a man with advanced PSP who received intravenous and intrathecal (into the spinal fluid) infusions of stem cells derived from umbilical cord blood.  His symptoms had started unusually young, at age 53, and 8 years later, his PSP Rating Scale score was 73 – a typical score for that duration of disease.  He received the infusions at that point and has survived another 8 years to date with essentially the same PSPRS score. 

Although the patient is (apparently, but not explicitly) still alive and there has been no autopsy to prove the accuracy of the diagnosis, the clinical history, neuro exam and published MRI images are typical for PSP.  The subtype is probably PSP-Parkinson, as his falls didn’t start until 3 years in and he didn’t need gait aids until 2 years after that.  The authors state that the subtype was PSP-Richardson syndrome because the patient met those criteria at the time they first saw him, 8 years in.  But PSP-P usually evolves into PSP-RS in the advanced stages.  The life expectancy of PSP-P with typical onset age in the 60s is about 10 years, and for those with onset as young as age 53, would be a few years more.  So survival (to this point) of 16 years is not far from expected.

But that’s not the main problem. The main problem is that the PSP Rating Scale has a “ceiling effect.”  That is, patients progress at an average rate of 10 or 11 points per year, and once the score reaches the 70s, it stops progressing although the patients continue to survive and to worsen.  That’s because the worst possible score on many of the scale’s 28 items doesn’t capture the full level of dysfunction that can yet occur.  Another reason for the ceiling effect is that some of the 28 items don’t affect some patients severely or at all, even late in the disease course.  Examples are dystonia, tremor, irritability, emotional incontinence, horizontal eye movement loss, and limb apraxia.  So the patient of Dr. Li et al may simply have reached his PSPRS ceiling and continued to survive by virtue of the unusually good general care that study subjects typically receive.

There are some other issues:

• There’s no objective evidence that the infused cells survived. 
• There’s no measure of any sort of growth factor in the blood or CSF that might provide a mechanism of action of stem cells in halting an otherwise rapidly progressive disease in its tracks. 
• There’s no functional measure of brain metabolism such as fluorodeoxyglucose PET or magnetic resonance spectroscopy to objectively document a halting/slowing of progression.
• The 2 MRI were performed at the time of the infusions and 2 years later.  Although the authors claim “no deterioration” in the MRI over that time, the 2 sets of images do show progression of atrophy, both to my eye and by the formal measurements superimposed on the images.  The midbrain’s diameter on the before-and-after sagittal images (Fig. 1, images A-1 and B-1) declined from 11.84 mm to 10.64 mm and the pons from 21.07 mm to 19.37 mm.  Both are typical for PSP.  The before-and-after axial images (images A-2, A-3, B-2 and B-3), where the measurements seem to indicate some improvement in the atrophy, are performed different scanning planes.  That can seriously affect the simple measurements performed. In fact, comparing the 2 sagittal images shows that the patient’s head is at 2 very different tilt angles in the scanner.  That problem affects the measurements in the axial plane but not in the sagittal plane.

As Dr. Li and colleagues point out, “randomized controlled trials are needed in the future . . . “ I would advise people with PSP not to undergo this, or any, experimental procedure outside of a formal trial at a reputable academic institution.  If you’re considering it, make sure the study is listed in clinicaltrials.gov, although that by itself no guarantee of anything.  Make sure that the researchers have a track record of peer-reviewed publication in this area.  If the doctors doing the treatment are willing to use it for a wide variety of unrelated disorders, be suspicious.  If the claims omit mention of side effects or toxicity, be doubly suspicious. If there’s no mention of success in any sort of animal model, that could be a problem.  Finally, if a “research study” charges a hefty fee, stay away. (We have no evidence that this was the case for Li et al.)

We should encourage fresh ideas for the treatment of PSP and other neurodegenerative diseases.  We should not be biased against research from countries with still-developing research infrastructure and institutional safeguards.  But we should also know how to evaluate the quality of research reports and to be vigilant for signs of quackery.