Advertisement
*
Reproduction permitted for personal use only. For reprints and reprint permission, contact reprints@wistechnology.com.

Madison-based Mithridion seeks to capitalize on Alzheimer's breakthrough

Springing out of a promising research breakthrough on Alzheimer's disease, UW-Madison researcher Jeff Johnson has co-founded Mithridion Inc. in hopes of commercializing an Alzheimer's-inhibiting drug.

Johnson and fellow researcher Thor Stein led a team that began about four years ago by asking a simple question: Why don't mouse neurons die when slammed by a protein thats been shown to kill human neurons in early onset Alzheimer's patients? From there, Johnsons team followed a trail that led to the identification of an amino acid-peptide sequence within a certain very long protein that encourages a protective response in the brain against the onset of Alzheimer's disease.

Mithridion plans to develop its new drug based on that sequence, which the Wisconsin Alumni Research Foundation, the university's licensing arm, has patented.

"If we can find a way to increase this protective pathway that mice have done indigenously themselves, I see no reason why we wouldnt be able to stop the progression of the disease wherever it was diagnosed at," Johnson said.

In the meantime, Mithridion's goal over the next 18 months is to take the drug lead that Johnson has in pocket and develop that into a drug candidate. "We now need to do some chemistry on the initial drug lead to find the ideal drug candidate," said Trevor Twose, CEO of Mithridion. Twose said the company is probably one year away from filing an investigational new drug application with the Food and Drug Administration and has put itself on a three-year timeline to get to Phase I clinical trials.

Quick formation


Mithridion, which draws its name from the word mithridate, an antidote for poison, has risen from combining the science of Johnson and Stein (soon to be Mithridion's chief scientific officer) with Twose's business experience. Twose, who did his post-doctoral work in Wisconsin 30 years ago, began working with Johnson just last September through Biopons, a professional services company for which he also serves as CEO. Biopons specializes in creating and developing homegrown biotech companies and also is working on relocating a couple of overseas companies here in Wisconsin.
Advertisement
Johnson sat down with Biopons in October to discuss the science behind the company and concocted a proposal for forming Mithridion. The company was formed November 19.

Twose said Mithridion will be seeking about $1.25 million in regional venture capital for its first two years of work. The company also is seeking SBIR/STTR grants from the government and support from the Department of Commerce.

Cause for hope


What gives great hope to Mithridion is that where other researchers ran into a dead end, Johnson and Stein were able to attack the problem from a different angle and progress.

When studying the causes of early onset, or familial, Alzheimer's disease, scientists have isolated a mutant gene called amyloid precursor protein. Much research has been done to engineer mice that over-expressed that protein in the hope that the mutation would accelerate in the mice and that scientists would obtain a fast model for research. That approach failed, Johnson said, when one of the hallmarks of Alzheimer's – excessive plaque in the brain – materialized, but the second – tangles in neurons that signify that they are dying – did not.

"There was no tangle formation at all, and really no neurons died in these animals," Johnson recalled. "So the big question was, What's wrong? These [mice] are basically a failed model of Alzheimer's disease because they don't recapitulate. They don't show the whole pathology. All we did was ask, 'Why don't neurons die?'"

What they found was that if the parent amyloid precursor protein was cut a certain way by a certain enzyme, it generated what is called a beta amyloid, which is a toxic protein that also is found in the plaque that leads to cells dying in the brains of Alzheimer's victims. But if that same parent protein is cut by a different enzyme, it generates another protein that counteracts the toxicity of the first.

"So it turns out that this 'good cut' protein from the big parent protein was actually causing this significant induction of these protective mechanism that blocked the bad protein toxicity. That was very interesting," Johnson remarked.

Though Johnson said it will be three to five years before the company can really begin to expand into larger drug trials, rather than trying to activate a foreign system within the human body or produce something altogether different, what Mithridion is trying to do is find drugs that will activate this indigenous system that protects against this pathway to toxicity, he said.

Early-onset Alzheimer's accounts for about 10 percent of all cases. As for the other 90 percent, Alzheimer's contracted sporadically and for no apparent reason, the condition "probably is due to an equilibrium balance shift between the good- and the bad-cut protein," Johnson said.

"So as you age, the good-cut protein goes down and the bad-cut protein goes up, and it's happening in everybody," he said. "The difference is probably when that switch starts occurring and the level at which these protective pathways are activated in each individual is based on their genetic background."

Twose is optimistic about the market for Mithridion's hoped-for drug treatment. The worldwide market for Alzheimer's drugs is about $2.8 billion and could be five to 10 times that when one considers that current drugs are taken by only 25 percent of patients. And with North America's Baby Boomers rapidly approaching the age at which Alzheimer's typically sets in, the number of sufferers is due to rise.

"There is enormous medical need," Twose said. "Alzheimer's is a devastating disease. Current drugs only help to allay the symptoms. What's really needed is a drug that stops the disease."

Lincoln Brunner is a WTN contributing editor and can be reached at lincoln@wistechnology.com.

Comments

Johann Nothnagel responded 9 years ago: #1

I would like to ask Jeff Johnson about the set time limit "three years to get to phase 1 clinical trials." If your mother or close one were ill with AD and the clock was ticking, would your set time limit also be the same? What about overtime and calculated short cuts?

Federal regulations make drug companies go through set stages of testing in order to weed out drugs that don't work. Overtime probably would not help, and short cuts are not allowed. — editor

pete mccreadie responded 8 years ago: #2

my father, director of the laboratory at children's hospital of milwaukee from 1960-1988, died in october from this insidious disease @ 86. my mother, 85, exhibits the synptoms and would probably classed in the middle stage of AD. please keep me updated on the progress of your research or any other relevant studies being done as the memantine and aricept are of questionable efficacy.
thank you very much for your time and attention!

pete mccreadie
319 arlington street, #3
waukesha, wi 53186
(262)-549-9816

S. Irving responded 8 years ago: #3

This terrible disease has affected several members of my family. My grandfather and his twin brother had it and my mother was one of 12 children, 6 of whom got it. Now it has hit four of my cousins that I know of. Our family has been davastated by it. I'm praying for a cure.

JOHANN NOTHNAGEL responded 8 years ago: #4

I wrote to you on 8 June 2005 inquiring aboutclinical trials. Any good news?
Thank you.

Clare S. Johnson responded 6 years ago: #5

Every time some wonderfully talented human beings, come up with help for Alzheimer's Disease, I want to thank them personally. I am an AZ Advocate, constantly harassng our government officials when any of our clinical trials are cut back. My husband of 41 years, was diagnosed with AZ when he was 64, two years ago. This is hard on our three children, who have jointly given us seven beautiful Grandchildren. Is this evil illness in store for them? All the work being done gives our family so much hope! Thank you!

-Add Your Comment

Name:
E-mail:

Comment Policy: WTN News accepts comments that are on-topic and do not contain advertisements, profanity or personal attacks. Comments represent the views of the individuals who post them and do not necessarily represent the views of WTN Media or our partners, advertisers, or sources. Comments are moderated and are not immediately posted. Your email address will not be posted.

WTN Media cannot accept liability for the content of comments posted here or verify their accuracy. If you believe this comment section is being abused, contact edit@wistechnology.com.

WTN InGroup
Advertisement
SupraNet Communications
WTN Media Presents