חידושים בטיפול ב-NASH: תרופות חדשות למחלת כבד שומני באופק

קפיצה לפרק

• מורכבות NASH ואתגרי הטיפול
• הסבר על הטרוגניות המחלה
• מגבלות הטיפול הנוכחי
• גישת הטיפול המשולב
• תחזית עתידית לטיפול ב-NASH
• תמליל מלא

מורכבות NASH ואתגרי הטיפול

ד"ר סקוט פרידמן, MD, מתאר דלקת כבד שומנית לא-אלכוהולית (NASH) כאחד האתגרים הגדולים ביותר בקריירה שלו. הוא מסביר ש-NASH מורכבת בהרבה ממה שהבנו בתחילה. המחלה כוללת מספר מאפיינים לרבות הצטברות שומן בכבד, דלקת, פגיעה תאית והצטלקות הכבד.

ד"ר סקוט פרידמן, MD, מדגיש שמורכבות זו מסבירה מדוע אף תרופה לא קיבלה עדיין אישור FDA לטיפול ב-NASH למרות מחקר נרחב. התכנות המטבולי הגורם לגוף לשמור על שומן הוא מובנה很深, מה שהופך התערבות טיפולית לאתגר מיוחד.

הסבר על הטרוגניות המחלה

ד"ר סקוט פרידמן, MD, חושף תובנה קריטית לגבי ההטרוגניות של NASH. מטופלים הנראים כסובלים מאותה מחלה under microscopy may actually have different underlying drivers. Some patients develop NASH primarily due to toxic fat accumulation, while others have overactivated stellate cells or specific inflammatory cell types.

ד"ר סקוט פרידמן, MD, מציין שאפילו התרופות המבטיחות ביותר ל-NASH בדרך כלל מועילות רק ל-30-50% מהמטופלים. זה מצביע על כך שקיימות multiple disease pathways within the NASH diagnosis category.

מגבלות הטיפול הנוכחי

הראיון עם ד"ר אנטון טיטוב, MD, בוחן מדוע גישות הטיפול הנוכחיות ב-NASH אינן מספקות. ד"ר סקוט פרידמן, MD, מסביר that blocking one pathway might drive compensation through other mechanisms. This multi-pathway nature of NASH creates significant treatment challenges.

ד"ר פרידמן מכיר בתסכול within the medical community about lacking approved NASH medications. He compares NASH treatment development to hepatitis C therapy, noting that viral targets are simpler than systemic metabolic diseases. The search for NASH's "Achilles heel" continues without clear single-target solutions.

גישת הטיפול המשולב

ד"ר סקוט פרידמן, MD, תומך בטיפולים משולבים כעתיד הטיפול ב-NASH. Multiple drugs with complementary mechanisms of action may be necessary to address the disease's complexity. This approach could target fat reduction, inflammation control, and fibrosis prevention simultaneously.

ד"ר פרידמן מציע that personalized medicine may become essential for NASH management. Treatment selection might depend on individual patients' dominant disease drivers. Combination regimens could involve two or more medications to achieve maximal therapeutic effect.

תחזית עתידית לטיפול ב-NASH

ד"ר סקוט פרידמן, MD, מספק תחזיות אופטימיות regarding NASH medication approvals. He anticipates the first FDA-approved NASH drugs will emerge within the next couple of years. However, he cautions that progress will be iterative and gradually progressive.

ד"ר סקוט פרידמן, MD, מדגיש the need for both aggressive drug testing and patience. Basic science discoveries must continue to identify new NASH treatment targets. The therapeutic landscape for fatty liver disease will evolve slowly but steadily toward more effective options.

תמליל מלא

ד"ר אנטון טיטוב, MD: מדוע אין עדיין תרופות מאושרות לדלקת כבד שומנית לא-אלכוהולית? זה למרות כל המחקר.

ד"ר סקוט פרידמן, MD: אתה חוקר renowned researcher in fatty liver disease and its genetics and metabolic effects. זה אחד האתגרים הגדולים ביותר that I've confronted in my career. It reflects the fact that NASH is a much more complex disease than we first gave it credit for.

We know that there are a number of features that occur in NASH. I mentioned most of them already: the liver fat, the inflammation, the injury, the scarring of the liver.

ד"ר אנטון טיטוב, MD: What we don't know is whether every patient who has NASH that we diagnose under the microscope has exactly the same disease.

ד"ר סקוט פרידמן, MD: It could be that some patients have NASH primarily because they have too much fat and the fat is toxic. Others because their stellate cells may be more activated, and others yet because they have too much of certain kinds of inflammatory cells.

So we're just starting to think about the fact that not all NASH is identical. Even if it looks the same under the microscope, it could be that the pathways that lead to the development of NASH may be different across different patients.

And that could explain why no drug has had a benefit in all patients. Even the drugs that look most promising typically only benefit about a third, at most half of the patients.

That may suggest that not everybody has the same disease drivers in their livers to cause the NASH picture, even if it looks the same under the microscope. It may also be that NASH is a multi-pathway disease.

And if you block one pathway, other pathways are driven to create more fat and inflammation. And so we may need multiple targets and multiple drugs with different mechanisms of action that are complementary.

That's sort of where the field is starting to go now. We think more about combination therapies for NASH because we want to hit more than one target.

And we don't really have a clear understanding of what is the Achilles heel from a treatment perspective. Is there one pathway in NASH, or is there one molecule that drives the disease in every patient with NASH?

So far, we haven't described that so-called Achilles heel. And so again, we're still left trying to use different combinations of treatments for NASH.

The programming of the body and the liver to hold on to fat is very hard-wired. And it's going to take a deeper understanding and a bit more patients before we come up with something that really will improve therapy of NASH.

I don't think we're far away in terms of our first approved drugs for NASH. I think we'll see that within the next couple of years.

But it will be an iterative, slowly progressive process where we may have to individualize therapies or combinations. And we may have to use even more than one or two drugs, as I mentioned, to get a maximal effect.

So yes, it's been very frustrating that we don't have an approved drug yet for NASH. In the greater scheme of things, I think the time horizon has been relatively short.

If you look at a disease that turned out to be easier to treat, that would be hepatitis C, even though we had the viral sequence as early as 1989. It was really only in 2010 that we finally developed really effective, well-tolerated curative therapies.

And frankly, hitting a virus is a lot easier than hitting a systemic disease like metabolic syndrome associated with NASH. And so, I think we need to be both assertive and aggressive in testing new drugs for NASH.

We must unearth more basic science discoveries that define targets in NASH. But we also need to be more patient in anticipating slow but steady progress in the therapeutic landscape of NASH.