After 18 years of studying the secret lives of cells and their RNAs, Spector’s team had zeroed-in on one culprit enabling breast cancer to spread: a long non-coding RNA called MALAT1. When healthy epithelial cells lining the surface of the milk ducts in the breast develop an excess of this molecule, they go bonkers. In biology, proper balance is key to health, so when some RNAs are overexpressed (meaning too many) or under-expressed (meaning too few), diseases can develop.
The overexpression of this RNA makes breast epithelial cells lose their biological sense of self and start proliferating and spreading. “They’ve lost control,” explains Robert MacLeod, chief scientific officer at Flamingo Therapeutics, a company that is collaborating with Spector. “Normal epithelial breast cells know what they have to do, such as produce milk proteins when needed. But cancer cells think they need to grow and survive and look for a new home and metastasize to new organs.” It is as if the rogue RNAs act like the cells’ molecular murder accomplices, enabling them to sneak around. “We showed that the MALAT1 RNA is involved in cells’ migration and metastases,” Spector says.
The next step was to see what happens if the amount of that RNA was reduced by a drug. To accomplish this Spector’s team and collaborators at Ionis Pharmaceuticals, a company that licensed the MALAT1 program to Flamingo Therapeutics, devised a clever molecular trick. They built a compound able to bind to the RNA akin to how two sides of a zipper or Velcro straps stick together. Called an antisense oligonucleotide, the compound consists of 16 nucleotides that are complementary to a specific region on the MALAT1 RNA so that when the two encounter each other in a cellular soup, they cling together. That marks the rogue RNAs for execution, molecular style. It sends a signal to a voracious team of enzymes that slice up the RNAs like miniature scissors. “When this oligonucleotide finds MALAT1 in the cells, it binds to it and stimulates the recognition by enzymes that will degrade the RNA,” Spector explains.
But the most surprising thing happens after that, says MacLeod. With the decreased amount of MALAT1 RNA in them, the cells recover some of their biological identity. “This drug seems to reprogram the cells and they suddenly remember who they are,” MacLeod says. “Oh, I am a breast epithelial cell, and I don’t need to metastasize and go someplace. Instead, I should do some things here at my home, such as supporting the mammary gland function.”
Spector’s team named their prospective therapeutic MALAT1 RX. They found that it stopped the cancer’s progression in mice and in organoids—the mini-tumors grown from the chunks donated by Kostroff’s patients. The next step would be trying it in living people in a clinical trial, which Spector hopes will happen within a year or two. “We are starting the conversation with the FDA,” MacLeod says.
For a typical drug development timeline, MALAT1 RX is moving fast. Even though Kostroff’s patients who so altruistically donated their tissues to Spector’s research may not benefit from this future drug, those a few years down the road may be luckier. “We started with no inclination that this may ever get to the clinic,” Spector says. “So the fact that we’re hoping to go to a clinical trial in about a year or two is extremely exciting. It would be a very significant triumph of fundamental research that we hope will really make a difference.”
- More Here
The most important take away is that to even have small progress to find good treatments (I am avoiding the word "cure" for obvious reasons), people have to sacrifice and donate data.
Your data is more precious than dollars if we want to make progress n healthcare!!
What Max went through shouldn't happen to any living being. Neo, Fluffy and Garph are living a healthy life from the lessons learned from Max's suffering. I donate their data and mine where ever it's needed. You should do so too.
No comments:
Post a Comment