The path to medical cures is not a linear one. A couple of years ago scientists appeared to be on the verge of regrowing human limbs. That research has stalled. They haven’t quit trying, they just haven’t had replicable success. A few years ago helping paralytics walk was limited to cumbersome, and expensive, exo-suits. Now clinical trials are ongoing using stem cells and physical therapy. I could go on, but you get the basic idea. What seems promising one day suddenly isn’t, and what seemed like science fiction is suddenly real. But that’s how science works. You learn from failure and repeat success. As one scientist I know likes to say “I’ve never failed at a single thing, but I’ve learned more than anybody should.” She’s part of a team attempting to cure diabetes. The external pancreas, which does allow a person to live without insulin or food issues, works, but it’s not a true cure. What they want is a shot, or series of medicines or treatments, that heal the body, not just work around a part of it.

Now, way way back in January of 2017. I wrote about a group of scientists who’d had a 100% cure rate with Alzheimer’s patients. I made sure to note that their study sample was insanely small, just ten people, but all ten were completely cured. They have started work on larger samples, and are moving forward to make this a reality for all.

Part of their program included some experimental stuff that wasn’t even being developed by its creators. The reasons for that were multitudinous, mostly business related, but the result was still the same. Possible cures were on drawing boards around the world and none of them were getting made.

One of those possible cures involved an esoteric vaccine called an Endobody.

The nice people over at United Neuroscience are kind enough to supply a plain language definition.

ENDOBODY

en • do • body   |   \’en-dō-bä-dē\   |   noun

1. def.: A substance produced by the body that counteracts the effects of other substances that your body produces
2. medical: A synthetically-induced physiological autoantibody that regulates biology
3. examples:
   • An endobody vaccine trains the body’s adaptive immune system to more efficiently and selectively produce antibodies against undesirable endogenous host proteins
   • Endobody targets include cancer cells, hormones, or neurotoxic proteins as aggregated beta-amyloid peptides

Even simpler, they train your body to eject bad things and replace them with good ones.

Easily said, almost impossible to do.

On June 24, Stephen Armstrong at WIRED Magazine, related the tale of Chang Yi Wang and Mei Mei Hu, a scientist mom and her business oriented daughter, respectively. The tale is long, weird, and portrays a relatively dysfunctional family. Anyway, back to endobody vaccines and their development. Read the whole thing if you can. It’s worth your time.

The vaccine research involved a new field in immunology called endobody vaccines. Most vaccines prepare our body’s immune system to fight off so-called exogenous disease, such as measles or flu, caused by bacteria or viruses entering our blood. Endobody vaccines, on the other hand, prime our immune system to deal with malfunctioning internal parts of the body that it would otherwise ignore.

Endobody vaccines are very rare, with only four approved for the market, two for cancer and two for animal healthcare – one of which was developed by Chang Yi in 2003. This particular drug can completely block the production of testosterone in the body and is currently used as a method of pig castration. “It’s like a teenager’s worst nightmare,” Mei Mei says with a dry smile. “Most men find their partner’s parents intimidating. My mother literally developed a drug that can cause men’s testicles to shrivel up and disappear.”

Okay, so that’s not daunting in the slightest.

But …

Mei Mei buckled in and took over the business side of her mother’s research. What had been a hot mess of disparate ideas, many conflicting, was honed down to one single company, United Neuroscience. The old company, United Biomedical, had its fingers in numerous pies, but this one was the one they realized could help save the world and make them boat loads of cash.

United Biomedical had other endobody vaccine candidates in development, the most interesting a vaccine for Alzheimer’s. This vaccine had already been successfully tested on small mammals and monkeys (baboons and macaques). Mei Mei wasn’t versed in the intricacies of the biochemistry so decided to get an outside opinion, approaching prominent vaccine researchers. They were blown away by her mother’s work. One investor suggested that she should search for other endobody vaccines that worked in the same way. Mei Mei couldn’t find any. Her mother had created something unique.

Upon this realisation, Mei Mei urged her mother to focus all her efforts on the Alzheimer’s vaccine through the spinoff company United Neuroscience. This was the chance of a lifetime, the opportunity to change the lives of millions. Chang Yi reflected for a few days before agreeing. She asked her daughter to be the CEO of the new company. She would return to the lab and finish the work she had started, she told her daughter. She was going to find a defence against Alzheimer’s disease.

While chemically castrating pigs, and curing Alzheimer’s might seem unrelated, the basic process for both was the same. They wanted to remove specific proteins and cause the body to generate a specific response. Again, simple to say. From 2003 until 2019, with the company only being restructured over the last couple of years, they finally came up with something that warranted human trials for Alzheimer’s patients.

For reasons that are unclear, damaged beta-amyloid can misfold into a “sticky” form that clumps together in a tangle of fibres – called plaques – that accumulate around nerve cells and disrupt cell communication, metabolism and repair. Tau can also misfold into an abnormal shape and clump with other tau molecules, forming threads that eventually join to form tangles inside neurons, blocking the flow of food.

Both proteins may cause brain cell damage, although researchers aren’t sure if high levels of beta-amyloid and tau cause Alzheimer’s or are symptoms of the condition. Both damaged versions of the proteins can cause neighbouring beta-amyloid and tau molecules to misfold as well – spreading the damaging tangles to other cells, breaking nerve cell connections with other neurons and slowly starving neurons to death.

The risks generally increase with age, but an inheritable form of the disease – early-onset Alzheimer’s – can affect people as young as 30. Symptoms begin with difficulty remembering recent events, progressing to problems with language, mood, motivation and orientation. Patients become isolated and confused as the disease progresses, shutting down physical functions. Some medications can reduce memory loss and aid concentration, but these just boost the performance of unaffected neurons, doing nothing to stop the kill-off of brain cells. There is no known cure. Following diagnosis, life expectancy is typically between three and nine years.

Chang Yi’s vaccine – UB-311 – couples a synthetic imitation of a common disease with a specific sequence of amino acids that are present only in the damaged beta-amyloid protein, and absent in the healthy form. This provokes an antibody response, clearing the tangled proteins away without provoking potentially damaging inflammation.

In January 2019, the company announced the first results from a phase IIa clinical trial in 42 human patients. “We were able to generate some antibodies in all patients, which is unusual for vaccines,” Chang Yi explains with a huge grin. “We’re talking about almost a 100 per cent response rate. So far, we have seen an improvement in three out of three measurements of cognitive performance for patients with mild Alzheimer’s disease.”

Phase IIa trials are small. So small that they’re considered statistically useless. But, they are considered proof of concept. And, for Chang Yi and Mei Mei, it’s opened up a world of possibilities.

Currently, United Neuroscience is proceeding with phase III trials for its Alzheimer’s vaccine, and has adapted the synthetic peptide technology to create vaccines for the hallmark protein in Parkinson’s disease. Known as UB-312, the Parkinson’s vaccine is just about to enter phase I testing. A third vaccine, targeting Tau, is in the pre-clinical phase. Tangled Tau proteins aren’t just a feature of Alzheimer’s – they’re also found in soldiers and athletes who face repeated or significant head injuries, hence the interest from the military.

So where are we at? I’ll let Chang Yi sum it up.

“What if you went to the doctor and they took a measurement that could record protein levels in your brain?” she begins. “If it’s too high, we give you a vaccine and keep toxic proteins at bay. You could do it in a kiosk in a mall or with an iPad at home, if this could be monitored through affordable blood tests or retinal scans. We’re starting work on an anti-migraine vaccine at the end of this year and the technology can be applied to anything.”

… For her, the goal is simply to take what she’s learned with Alzheimer’s and use it to treat everything from cancer to HIV. “If we can do that, I would feel my life’s purpose has been satisfied,” she nods. “My parents gave me the name Chang Yi which, in English, means Always Happy. If we cured Alzheimer’s I would be very happy.”

Follow up research says the Phase III trials are moving along and they hope to be commercially viable later this year. That would be a nice Christmas present for people dealing with Alzheimer’s.

And if it doesn?

The team I mentioned above has also moved into Phase II testing.

At this point it’s no longer a question of “if” Alzheimer’s can be cured, but when and by which method.

By the way, there’s absolutely no reason both may not have value.