MRI-Guided Intraarterial Catheter-Based Method for Predicting Territory of Local Blood Brain Barrier Opening
Patent Number: US20170079581A1
Executive Summary:
General Description:
The blood brain barrier is a highly selective membrane that has been a large hurdle for drugs being delivered to the brain. Typically, only small, hydrophobic molecules are able to cross the BBB; as a result, the BBB selects and screens out ~95% of compounds for drug development. This new MRI-guided, intraarterial catheter-based method allows for highly precise drug delivery to the brain through blood brain barrier disruption at specifically controlled regions
Scientific Progress:
In 2018, real-time MRI imaging of opening the Blood Brain Barrier using hyperosmotic mannitol was performed in mice in which the critical parameters, such as perfusion rate in the carotid artery and infusion velocity of the mannitol, were well described showing that this method is reproducible and can be targeted to a specific region for drug delivery.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal status: Pending
Publication PMID: 26661231, 30416485
Publications:
Janowski M, Walczak P, Pearl MS. Predicting and optimizing the territory of blood-brain barrier opening by superselective intra-arterial cerebral infusion under dynamic susceptibility contrast MRI guidance. J Cereb Blood Flow Metab. 2015;36(3):569-75.
Chu C, Liu G, Janowski M, Bulte JWM, Li S, Pearl M, Walczak P. Real-Time MRI Guidance for Reproducible Hyperosmolar Opening of the Blood-Brain Barrier in Mice. Front Neurol. 2018 Oct 26;9:921.
Inventor Bio: Piotr Walczak
https://www.hopkinsmedicine.org/profiles/results/directory/profile/5840468/piotr-walczak
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/US20170079581A1
- Related Patent Link: https://patents.google.com/patent/WO2015179258A3
- Research Institute: Johns Hopkins University
- Disease Focus: Gliomas
- Basis of Invention: Intraarterial Mannitol+Catheter Induced Blood Brain Barrier Opening (BBBO)
- How it works: Real-Time MRI imaging of catheter-based intraarterial injection of Mannitol to the Blood Brain Barrier to visualize local brain parenchymal disruption as a drug delivery method
- Lead Challenge Inventor: Piotr Walczak
- Inventors: Piotr Walczak, Monica Pearl, Miroslaw Janowski
- Development Stage: Preclinical
- Novelty:
- Method for creating a non-invasive opening for drug delivery within the Blood Brain Barrier (BBB)
- Clinical Applications:
- Provides a well-controlled and visualized (through MRI) drug delivery method to pass through the Blood Brain Barrier
General Description:
The blood brain barrier is a highly selective membrane that has been a large hurdle for drugs being delivered to the brain. Typically, only small, hydrophobic molecules are able to cross the BBB; as a result, the BBB selects and screens out ~95% of compounds for drug development. This new MRI-guided, intraarterial catheter-based method allows for highly precise drug delivery to the brain through blood brain barrier disruption at specifically controlled regions
Scientific Progress:
In 2018, real-time MRI imaging of opening the Blood Brain Barrier using hyperosmotic mannitol was performed in mice in which the critical parameters, such as perfusion rate in the carotid artery and infusion velocity of the mannitol, were well described showing that this method is reproducible and can be targeted to a specific region for drug delivery.
Future Directions:
- First-In-Human studies and possibilities for co-development of an in vivo companion medical device.
Strengths:
- Provides reproducible and precise method to reversibly open the BBB involving intra-arterial injection (IA) of a hyperosmolar agent (i.e. Mannitol) combined with non-invasive MR imaging to accurately predict the territory of BBB opening
- Can be useful in treating not only brain cancers, but also neurological disorders such as Alzheimer’s, cranial nerve disorder, seizure disorder, etc.
Weaknesses:
- Not yet tested in humans
- Greater risk of bacterial infections/contaminations during catheter incorporation as well as the challenge of delivering effective and sustained treatments to damaged cells without harming the healthy brain tissue in the surrounding areas
- May not be as effective as post-resection drug delivery for treatment of brain tumors/disorders
Patent Status:
Legal status: Pending
- Priority date: 2014-05-17
- Filing date: 2015-05-17
- Publication date: 2017-03-23
Publication PMID: 26661231, 30416485
Publications:
Janowski M, Walczak P, Pearl MS. Predicting and optimizing the territory of blood-brain barrier opening by superselective intra-arterial cerebral infusion under dynamic susceptibility contrast MRI guidance. J Cereb Blood Flow Metab. 2015;36(3):569-75.
Chu C, Liu G, Janowski M, Bulte JWM, Li S, Pearl M, Walczak P. Real-Time MRI Guidance for Reproducible Hyperosmolar Opening of the Blood-Brain Barrier in Mice. Front Neurol. 2018 Oct 26;9:921.
Inventor Bio: Piotr Walczak
https://www.hopkinsmedicine.org/profiles/results/directory/profile/5840468/piotr-walczak
