colchicine in scd

Transcript

• 00:00Hello.
• 00:01I'm John Roberts. I'm a
• 00:03doctor and a clinical researcher.
• 00:07I'm,
• 00:09proposing to cures within reach
• 00:11that we repurpose
• 00:12the drug
• 00:13colchicine
• 00:15as a treatment for sickle
• 00:16cell disease.
• 00:18Sickle cell disease is an
• 00:19inherited disease characterized by anemia
• 00:22that is low red blood
• 00:24cell counts,
• 00:25acute and chronic pain, organ
• 00:27damage, and early death.
• 00:30Sickle cell disease affects millions
• 00:32with majority living in Sub
• 00:34Saharan Africa.
• 00:35Most in though in that
• 00:37location die before the age
• 00:39of five and survival is
• 00:41beyond thirty years is uncommon.
• 00:44Sickle cell disease is due
• 00:45to a mutation in hemoglobin.
• 00:48That's the,
• 00:50molecule in red blood cells
• 00:51that,
• 00:52binds and then releases oxygen
• 00:54to tissues.
• 00:56The mutation leads to red
• 00:58blood cell fragility,
• 00:59which leads to
• 01:01hemolysis,
• 01:03and anemia. And also the
• 01:06the hemolyzed red blood cells
• 01:08clump
• 01:09and then they can cause
• 01:11occlusion of very small blood
• 01:13vessels.
• 01:16So the primary processes are
• 01:17hemolysis and microvascular
• 01:19occlusions,
• 01:21but these lead to an
• 01:22important secondary process which is
• 01:25sterile inflammation,
• 01:27otherwise known as,
• 01:29activation of the innate immune
• 01:31system.
• 01:32We hypothesize that colchicine would
• 01:35reduce inflammation
• 01:36and improve outcomes in sickle
• 01:38cell disease.
• 01:40Colchicine is a drug of
• 01:41choice in several disorders
• 01:43of sterile inflammation, for example,
• 01:46gout
• 01:47and familial Mediterranean
• 01:48fever fever.
• 01:50It also is beneficial in
• 01:51atherosclerosis,
• 01:53which is another disease like
• 01:55sickle cell disease in which
• 01:57sterile inflammation is a secondary
• 01:59process.
• 02:00Colchicine
• 02:01is generic,
• 02:02inexpensive, and well tolerated in
• 02:04low doses,
• 02:05but it has never been
• 02:06studied in sickle cell disease.
• 02:08C reactive protein is a
• 02:10blood biomarker of inflammation that
• 02:12is chronically and acutely elevated
• 02:15in sterile inflammation,
• 02:16including in sickle cell disease.
• 02:18In a study in transgenic
• 02:20mice, we found that colchicine
• 02:22lowered c reactive protein.
• 02:24This suggests that colchicine might
• 02:26lower c reactive protein and
• 02:28improve the lives of people
• 02:29with sickle cell disease.
• 02:31A definitive trial of this
• 02:33concept would be a multicenter
• 02:34randomized placebo controlled trial
• 02:37which would cost tens of
• 02:38millions of dollars or more.
• 02:40This is not likely to
• 02:41be undertaken in the absence
• 02:42of preliminary evidence of effectiveness
• 02:45as well as the safety
• 02:46and tolerability
• 02:48of colchicine
• 02:49in people living with sickle
• 02:51cell disease.
• 02:52The next step then should
• 02:53be an early phase clinical
• 02:55trial to demonstrate that colchicine
• 02:57lowers c
• 03:00c reactive protein,
• 03:01a sign of,
• 03:03potential effectiveness,
• 03:04and that it is tolerable
• 03:06and safe in sickle cell
• 03:07disease.
• 03:08Thank you very much.