Today, "Forbes" published a story detailing a "milestone moment" in the history of LRRK2 and the linchpin role of The Michael J. Fox Foundation (MJFF) in ushering this promising genetic target forward.
Timed to the Foundation's annual scientific conference, Denali Therapeutics -- a San Francisco-based biotech -- presented data from its Phase I LRRK2 trial to more than 300 Parkinson's researchers and industry professionals. As reported in the story, Denali's Phase I study, which investigated the drug in healthy volunteers, sought to answer two important questions:
"Can the LRRK2 drug block the LRRK2 enough that it might work in Parkinson's patients? Can it do so without serious side effects, particularly in the lungs, or related to blood pressure? The answer to both questions appears to be yes."
A few years ago, after researchers published preclinical findings showing a LRRK2 inhibitor led to changes in lung tissue, the LRRK2 target was nearly stalled. Then, "the Fox Foundation stepped in." MJFF brought together three competing companies developing LRRK2 drugs for Parkinson's through the LRRK2 Safety Initiative. The Initiative demonstrated that LRRK2 inhibitors were safe for human testing, allowing continued investment and research. This industry consortium, coupled with preclinical funding from The Michael J. Fox Foundation, ensured the next phase of LRRK2 drug development could advance.
MJFF Senior Vice President of Research Programs Brian Fiske, PhD, explained the significance of this new data:
"For us, it's very exciting and promising to see that a LRRK2 inhibitor has entered human testing. Obviously that's the first step for testing people with Parkinson's. This was kind of a milestone moment."
MJFF's online clinical study Fox Insight is accelerating breakthroughs by capturing the experiences of people with and without Parkinson's. Through a collaboration with consumer genetics company 23andMe, people with Parkinson's who join Fox Insight can access the 23andMe Health + Ancestry Service at no cost and add their genetic information to the study. Register at foxinsight.org.
https://www.michaeljfox.org/foundation/news-detail.php?milestone-moment-parkinson-drug-moves-forward-with-help-from-michael-fox
Milestone Moment: A Parkinson’s Drug Moves Forward With Help From Michael J.Fox
Healthcare I cover science and medicine, and believe this is biology's century.
Brad Paisley and Michael J. Fox play together at the Fox Foundation's 2017 "A Funny Thing Happened On The Way To Cure Parkinson's" fundraiser.
Today, at a medical conference being hosted by the Michael J. Fox Foundation, a biotechnology company is presenting the first human data from a Parkinson’s drug that several of the world’s largest drug companies nearly abandoned.
The company, Denali Therapeutics, is run by a widely respected team that formerly worked at Genentech, the Roche unit, and it had one of the largest biotech initial public offerings of 2017. But the stock is down 16% from its IPO price.
Denali’s drug targets a protein called LRRK2 that is involved in cells' trash-disposal systems. The gene that makes it is the most common genetic cause of Parkinson’s. The LRRK2 gene variant was discovered 15 years ago. Sergey Brin famously carries a copy of it. 23andMe, the consumer genetics startup, has studied it. Pfizer, Merck and Genentech were all working on drugs targeting the gene when it was discovered that those drugs seemed to cause worrisome lung changes in animals. They all stopped work on it. At that point, this promising genetic hint to a Parkinson’s treatment looked as if it would never be investigated.
Then the Fox Foundation stepped in, organizing meetings at which all the companies developing LRKK2 drugs pooled their results and tried to understand what might have gone wrong. The team at Genentech — now the team at Denali — was part of those meetings, and they started their own company and licensed the Genentech molecule. That’s the drug on which data is being presented today.
The current study doesn’t involve any patients known to have Parkinson’s. But it can answer two very important questions: Can the LRRK2 drug block the LRRK2 enough that it might work in Parkinson’s patients? Can it do so without serious side effects, particularly in the lungs, or related to blood pressure? The answer to both questions appears to be yes.
There was a slight numerical difference between the placebo group and the various groups that received different doses of Denali’s drug. But the effect didn’t worsen as doses got higher, was not statistically significant, and does not appear clinically relevant. “The differences you see across these dose levels are not clinically meaningful and don’t support a dose-related effect,” says Carole Ho, Denali’s chief medical officer. Changes in blood pressure were also small, and didn’t seem to follow any pattern related to the drug. And, not directly related to the drug, genetic studies of people with mutations in the LRRK2 gene don’t seem to have any lung problems.
The next step will be to test Denali’s LRRK2 drug in patients with Parkinson’s — both those whose disease is caused by a LRRK2 mutation and those whose Parkinson’s is not related to LRRK2. (Researchers think that such a medicine might help those people, too.) Ho says that Denali plans to dose the first patient in those studies by the end of the year. One big difficulty will be finding Parkinson’s patients with the LRRK2 genetic variant. Denali has partnered with Centagene, a genetic testing company, to help find them. GlaxoSmithKline, which is also moving forward with a LRRK2 inhibitor, has partnered with 23andMe, and will reach out to patients in the 23andMe database who have the LRRK2 variant.
“For us, it’s very exciting and promising to see that a LRRK2 inhibitor has entered human testing,” says Brian Fiske, a senior vice president at the Fox Foundation. “Obviously that’s the first step for testing people with Parkinson’s. For us, this was kind of a milestone moment.”
https://www.forbes.com/sites/matthewherper/2018/10/25/milestone-moment-a-parkinsons-drug-moves-forward-with-help-from-michael-jfox/#1d5013f155a2
No comments:
Post a Comment