Ependymin-dervied Drugs: Behind CereMedix's Absurd Claims A few days ago the headlines read "LIVING TO 120 WITH EASE", "This man could help you live to 120", and "MIRACLE PILL". While the claims that the pill which they describe will get everyone to age 120 seem unfounded, the fashion with which it purportedly increases longevity brings up many interesting topics in aging.

The pill is being developed by CereMedix, a biotech startup at Northeastern University headed by CEO Steve Parkinson and president and lead researcher, Victor Shashoua. The products related to this "miracle pill" are centered around a class of glycoproteins called "ependymins," which are found predominantly in the cerebrospinal fluid of teleost fish (bony fish, eg. goldfish). Ependymin was discovered by Shashoua almost 30 years ago, and there have been many studies implicating ependymin in memory processes in teleost fish (ependymin has been found to play a significant role in memory formation and consolidation in goldfish (1, 2)). But study of ependymin is useful for more than just goldfish memory, as the mammalian gene UCC1 that is upregulated in colorectal cancer is found to have a similar genetic sequence (1, 2, 3, 4). It codes for a protein appropriately dubbed MERP1 (mammalian ependymin-related protein gene). The memory-regulating role ependymin plays in fish, as well as the mammalian homologue of its gene, beg the question "is ependymin neuroactive?"

To pursue the activity of ependymin related compounds Shashoua and others tested small peptide components of the ependymin molecule. Aministration of peptide fragment CMX-8933, a proteolytic cleavage product of ependymin, was found to activate the AP-1 transcription factor in rat brain cortical cultures. Activation of AP-1 is associated with neuronal growth. Additionally, this peptide was found to upregulate superoxide dismutase, one of the body's primary antioxidant enzymes. Free radicals have been implicated in forms of dementia such as Parkinson's and Alzheimer's, and thus the antioxidant-boosting activity of CMX-8933 might prove of clinical use. As a small peptide CMX-8933 can more easily cross the blood brain barrier than the whole ependymin molecule, thus increasing the potential of being used as a "therapeutic peptide."

Based on the results with CMX-8933, another peptide called CMX-9236 was synthesized with similar structure. It is 14 amino acids long and a combination of ependymin and calmodulin, calmodulin being a protein that mediates many calcium-driven metabolic reactions in eukaryotes. To one part of the molecule they complexed a docosahexaenoic acid (DHA) that enchances entry through the blood-brain barrier. CMX-9236's calcium-binding sites are thought to explain why it is neuroprotective in rat stroke experiments. When cerebral ischemia (blockage of oxygen/blood-flow) was induced in the rats to model stroke, CMX-9236 significantly reduced the damage done (41% +/- 20% damage reduction). Shashoua recounts from what I believe to be an experiment with CMX-9236 where stroke was induced in two rats and then one given CMX-9236:

"Around 6pm we left the laboratory for a meal. When we returned two hours later, the control rat -- the one which had had no treatment -- was still flat out, paralysed. The other was moving around feeding and drinking. The effects of the stroke had been almost completely reversed.

"Later when the animals brains were dissected, we could see the normal damage that one might expect from the stroke had been almost completely prevented. The brain appeared near normal

"Geriatric mice at the end of their lives were given an ependymin derived peptide [probably CMX-9236]. Then their activity was monitored as they criss-crossed closed boxes, breaking light beams."

The effect of the drug supposedly did not wear off, and this alleged restoration of youthful vigor in geriatric mice seems to be what is sparking the labelling of this drug as a fountain of youth. I was unable to find anywhere evidence of the experimentation with geriatric mice, which really would be the only piece of information about the ependymin-derived drugs that might warrant them being called "anti-aging drugs." The sustained reinstatement of youthful vigor from geriatric state or augmentation of longevity are by definition the only criteria that would permit a scientist to say a drug is "anti-aging" or that it would add extra years to one's life. While there seem to be many claims by CereMedix that its drugs will allow you to "live to 120 with ease" there seems to be absolutely no evidence of this whatsoever by their published experiments. The same goes with their geriatric mice experiments that don't seem to be published. Additional claims by recent CereMedix articles (see first three links of this post) seem just as absurd:

"the new pill has the equivalent effect of eating 30 lbs of fruit and vegetables every day."
While 30 lbs of fruit may contain an equivalent concentration of ependymin that is used in promising experiments, fruits and vegetables don't simply contain ependymin and then filler. The statement implies that their drug has condensed the nutrititve value of fruits and vegetables to a substitute drug, which is absurd.

"Everyone taking a pill will feel better and have more energy. Instead of pumping the patient full of chemicals we will be giving them a more natural drug."
The published promising experiments deal with derivatives or synthetic mimetics of ependymin, not ependymin itself, so the company's above claim is unfounded because the derived drugs don't exist in nature (as in, they DO want to pump patients full of chemicals). If I interpreted this wrong and they plan on using ependymin and not the derivatives as a product, it won't cross the blood brain barrier well and therefore won't be as useful as a neurological therapeutic drug. Additionally, the evidence for ependymin alone being therapeutic is ambiguous from published experiments.

"genetically, humans are capable of living between 120 and 160 years. However, few even come close, he says, because the human body is unable to repair the damage caused by aging."
Interestingly, CereMedix cites the genome project as for the preceding information (I can't find any such information on Genome Project pages). The average lifespan is about 75 years old for current citizens of the USA by government sites (1, 2). The oldest person I am aware of is Jeanne Louise Calment, who lived to the age of 122. To hint that the drugs they're developing are going to make one live to 160 years of age is astoundingly asinine.

"For smokers and others suffering from lung disease, the only drugs we have to offer at the moment are palliative. Even smokers who have given up suffer from breathlessness and worse. One hope is that the new drug can reverse this.'
Free radicals might play a role in damage resulting from smoking, and antioxidant-related drugs such as CereMedix's might lessen damage done when free radicals are present. However, after the carcinogenic components of smoking have done their damage to DNA, a drug that potentiates antioxidant systems alone will likely do little to alleviate smoking-induced symptoms.

In summary, the ependymin-related drugs have some very promising results with the ischemic rat experiments and the induction of antioxidant systems, and these results make the drugs good candidates (as of this writing public information does not suggest them anything more than candidates) for being used to treat neuropathological disorders. When it comes to CereMedix's PR department and faculties, it is sad that bravado and the presentation of ungrounded wild claims is taking the place of the presentation of experimental evidence and known facts. While such bravado has been abundant on the net and years past when dealing with products labelled such things as "fountains of youth" or "immortality elixers," etc. one would think that the fact that CereMedix is an outgrowth of Northeastern University and Shashoua's scientific reputation would separate CereMedix from such hogwash. Hopefully the ludicrous press that CereMedix is putting out will not scare off intelligent investors from thinking CereMedix has no substantial product. For us to know whether or not the ependymin-derived drugs have a future in true anti-aging medicine, we'll have to wait for CereMedix to publish their experiments and the results from their upcoming clinical trials which start next year in Scotland.