Some skepticism was called for in science writers’ responses to the news that a protein from human umbilical cord blood improves memory in aging mice. Most posts I saw included caveats of some sort, although in a few cases they were minimal.
For instance, Sumit Passary at TechTimes repeated only the pro forma cautions that mice-are-not-people and that even if the protein’s rejuvenating properties prove out, a human therapy would still be many years away.
But others were clearer about the counterarguments and uncertainties surrounding the protein’s capabilities.
The protein is TIMP2. It inhibits a group of enzymes called metalloproteinases (or metallopeptidases), which break down molecules that provide structural and biochemical support to cells. TIMP2 appears to be critical to maintaining tissue homeostasis.
BLOOD REJUVENATION SCIENCE SINCE 1863
The most thorough and cautious exploration of TIMP2’s potential came in a longish post from Ed Yong at The Atlantic. He summarizes past research–some dating back to 1863!–showing that young blood seems to rejuvenate several organs in older individuals, including the brain.
(In 1863, “French physiologist Paul Bert surgically stitched together the blood supplies of two mice, with a technique called parabiosis that has since been used to study cancer, the immune system, organ transplants—and aging.” Yong also points out that this real-world research links uncomfortably with the fictional world of vampire tales. A blood-as-rejuvenation connection with vampires has also been noted by others, such as Ronald Bailey at Hit & Run.)
CAN ALKAHEST TURN BLOOD PROTEINS INTO GOLD?
Yong reports that a juicy feud is developing between Irina Conboy, who does rejuvenation research at Berkeley, and the Stanford senior author of the new paper, Tony Wyss-Coray. In addition to her scientific objections to some conclusions the Stanford group has drawn from its research, Conboy charges that financial interests are shaping their views.
Wyss-Coray has launched a company, Alkahest, to identify rejuvenation molecules. (Fun etymological fact, perhaps not irrelevant: alkahest, a sham Arabic word, was the universal solvent sought by alchemists. Paracelsus believed it could turn base metal into gold.)
Alkahest is running a small clinical trial (18 subjects) looking at delivery of plasma from young donors on Alzheimer’s disease. I can’t resist sharing its title with you; the gyrations involved in devising a memorable acronym for a clinical trial are always entertaining: The PLasma for Alzheimer SymptoM Amelioration (PLASMA) Study. Results have not yet been published.
There’s also a startup called Ambrosia, which is charging customers $8000 for transfusions of young plasma. (Another fun etymological fact: ambrosia means “immortality” in Greek. Ambrosia was thought to be the food of the gods that conferred immortality, or at least longevity, on mortals who consumed it. That was before it became a fruit salad of oddments often featuring citrus, pineapple, coconut, and miniature marshmallows.)
“They’re treating anybody—people with Lyme disease, Alzheimer’s, people who are old and rich, whoever wants to get treated,” Wyss-Coray complained to Yong. “They claim they’re doing a clinical trial but I think every serious scientist agrees that this is abuse of the term. I think that they’re harming the whole field.”
TIMP2 vs EXERCISE?
Conboy also shared her complaints about the new paper with Jocelyn Kaiser at Science. Conboy “notes that the paper doesn’t put the modest memory and learning improvements from TIMP2 in context by comparing them to, say, putting an old mouse on an exercise wheel, which can also improve cognitive function.”
TIMP2 has broad effects, increasing the difficulty of figuring out exactly how it might be contributing to memory. Conboy pointed out to Angela Chen at The Verge that TIMP2 is actually high in Alzheimer patients, so it’s hard to argue convincingly that it’s low levels of the protein that are damaging cognition.
Conboy believes more than a single factor is probably involved. “I am sure there is not just one silver bullet,” she said. (She meant magic bullet, but never mind.) And once again Conboy mentioned researcher relationships with Alkahest, noting, “there is a very high temptation to say this is a miracle drug.”
Some are worried about potential negative consequences of administering TIMP2. That uncertainty gives even the new study’s enthusiastic first author pause. Joseph Castellano told Rae Ellen Bichell at Shots that even if TIMP2 and other blood proteins are beneficial for babies, they might not be good for older people. He said, “Maybe there’s a reason that older brains aren’t exposed to certain proteins any longer.”