Although Alkahest and Ambrosia were inspired by the same studies, their goals and approaches to research are very different.

The Academic

Stanford professor Tony Wyss-Coray co-founded San Carlos-based Alkahest in 2014, based on his findings that transfusions of young blood into old mice improve learning and memory and promote the growth of new connections between cells in the hippocampus. That’s a key memory center located in the middle of the brain. Alkahest is now working to translate these benefits to patients with Alzheimer’s disease.

In 2014, Alkahest sponsored an FDA-approved clinical trial at Stanford to give Alzheimer’s patients between the ages of 50 and 90 four small, weekly transfusions of plasma. The plasma is obtained from the Stanford Blood Center, which has a dedicated research arm that accepts blood donations specifically for Stanford clinical trials.

Joe McCracken, vice president of business development at Alkahest, says that for now, the study is focused on safety and feasibility rather than the efficacy of the treatment.

“We’re trying to avoid creating expectations of a Eureka moment that we’ll have people who have severe Alzheimer’s disease acting as though they’re adolescents again,” he says. “The expectation we have is that we will demonstrate that administration of young plasma to elderly patients with Alzheimer’s disease is safe.”

The patients are also undergoing memory assessments, brain scans and blood tests to detect any potential changes in disease symptoms. The trial has completed testing on all 18 patients, and McCracken hopes to publish the results by the end of the year. If all goes well, Alkahest plans to conduct a second, larger study to test for efficacy.

The company’s long-term goal is to identify the proteins in the blood that change with age, and then synthesize these factors into pharmaceutical drugs.

The Entrepreneur

Jesse Karmazin, CEO of Ambrosia, is taking an unconventional—and more controversial—approach to anti-aging research. Ambrosia, which has clinics in Monterey, California and Tampa, Florida, acts as a “pay-to-play” clinical trial, giving one large plasma transfusion to anyone over the age of 35 for a fee of $8,000. The plasma is purchased from local blood banks, which often have a surplus of the material because hospitals typically only require red blood cells for medical procedures.

Karmazin, who graduated from Stanford medical school, has gotten some heat for the price his participants are paying. He says his company has no investors, and without the fee the clinic and the study would be impossible. In contrast, Alkahest received a $37.5 million investment in 2015 from Grifols, a Spanish-based company that is the leading producer of blood- and plasma-based products.

“You don’t think about it, but you—or your insurance company—ultimately pay for the clinical trial over 20 years after the drug has been approved,” Karmazin says. “Companies patent the drug, they pay up front tens or even hundreds of millions of dollars [for a clinical trial], and then they hope to make a billion dollars over the next 20 years.”

Karmazin also justifies the cost of his study by saying that what people choose to do with their money is their decision.

“This amount of money for some people is nothing,” he says. “Not for me, I have $200,000 in loans.”

Ambrosia is analyzing data from its first 60 participants to look for changes in biomarkers of aging in the blood taken one month after treatment. The company doesn’t have any conclusive results yet.

It’s difficult to say whether Ambrosia’s study, as designed, is capable of producing conclusive results. Karmazin is accepting people with a vast range of ages and with different diseases or reasons for wanting the injection. That means the amount of data he gathers on any one condition will likely be limited and may not be useful.

The Question of Ethics

Neither company would comment on the work of the other, although Wyss-Coray took some shots in an article in Science last year, saying that Karmazin was “basically abusing people’s trust and the public excitement around” the research.

Bioethicist Karen Maschke from The Hastings Center, a research institute in New York, says the payment model of the Ambrosia trial “raises a lot of a red flags,” and that the design of the study sounds “very suspect.” She is particularly concerned that participants will think they are paying for a known therapy when in fact they are paying for an experimental and unproven procedure.

For his part, Karmazin says that he is "totally transparent that it is experimental.” Consent documents for the trial do describe the procedure as experimental and do not guarantee any improvements.

There have been no serious adverse events from the transfusions reported by either company, and both researchers are optimistic the treatment will provide real benefits to patients.