FDA Filing Made Requesting Use of Medtronic SynchroMed Pump To Deliver Cyclodextrin To Brain

To say I am pumped up  today is an understatement!  We’ve reached another historic milestone in our effort to treat Addi and Cassi with cyclodextrin!  Dr. Caroline Hastings at Children’s Hospital Research Center Oakland filed a 400+ page document with the FDA yesterday on behalf of the twins seeking a permanent solution to deliver hydroxyl-propyl-beta-cyclodextrin (HPBCD) past the blood-brain barrier and into the cerebrospinal fluid (CSF) by utilizing a Medtronic SynchroMed® II Drug Infusion Pump System.

We believe that combination therapy of intravenous (IV) and intrathecal (IT) HPBCD is the most effective way to target both the brain (IT) and organs/peripheral tissues (IV) in Niemann Pick Type C disease.

The FDA has been very helpful throughout this process but the FDA filings are incredibly time consuming and take months and months of work.  The amount of detail necessary for a new drug treatment protocol is mind blowing — even if it’s for two children with an ultra rare disease.  The reason is everything we do has implications for all other children with Niemann Pick Type C, not to mention other diseases where cyclodextrin may work.  I think it could work in the ‘Lorenzo’s Oil’ disease called adrenoleukodystrophy.  Check out this paper where cyclodextrin is having an effect in ALD:  ADRENOLEUKODYSTROPHY Cyclodextrin Paper.  I hope  ALD families are making their researchers pump this into their mice models.  HPBCD is safe — if it has an effect on VLCFA, it could go into ALD kids as well with this pump idea!

We’re proposing to the FDA to use a new drug (hydroxyl-propyl-beta-cyclodextrin) in an existing device (a SynchroMed pump).  This requires two FDA divisions to be involved in the approval process — the Division of Gastroenterology Products (DGP) which is part of the Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH), which is responsible for regulating firms selling medical devices in the United States.

I am sure anyone who works in the drug development field can appreciate the complexities involved when seeking FDA approval for a new drug in a device.  We don’t have time on our side and getting agreement from two FDA divisions is not easy.  But our plan is solid and makes sense and I am confident we’ll get the approval to move forward.

Once we get the Medtronic pump solution approved by FDA, Dr. Peter Sun, Chief of Pediatric Neurosurgery at Children’s Hospital & Research Center Oakland, will surgically implant a SynchroMed® II Drug Infusion System into Addi and Cassi.  We are proposing placing the catheter in the mid-thoracic region of the spine at the T6—T7 level rather than at the typical T11—T12 level.  Then HPBCD will be pulsed in bolus doses into the twins’ central nervous system so it can reach their brains.

To understand how this works, think about how a diabetic pump works.  Instead this pump is surgically implanted on inside of the body and is programmable from outside the body.  Generally, Synchromed pumps are used to deliver a drug called Baclofen used to control pain or spasticity.  In our case, we want to fill the pump with HPBCD monthly and deliver it just like you would Baclofen.

We have now completed 11  intratehcal injections of hydroxyl-propyl-beta-cyclodextrin into the twins’ spines via lumbar punctures. Intrathecal treatments are going very well but the travel from Nevada to California every other week is exhausting.  In addition, the sedations with propofol (yes, the one Michael Jackson used) take a toll on the twins. We really need a permanent solution and we believe SynchroMed is it!

Thanks to the amazing doctors and medical pros at Johnson & Johnson and Medtronic who have donated their time pro-bono to help us create this ground breaking treatment protocol.  The support we have received from people outside the Niemann Pick Type C community has been remarkable to say the least.

Now we wait to hear from the FDA to find out when we can schedule a teleconference call to discuss our proposal.