Posts Tagged ‘blood brain barrier’

English: Schematic sketch showing the transpor...

English: Schematic sketch showing the transport types at the blood-brain barrier. Deutsch: Schematische Darstellung der Transportmechanismen an der Blut-Hirn-Schranke. Français : Schéma des types de transport à travers la barrière hémato-encéphalique (Photo credit: Wikipedia)

Larry H Bernstein, MD

Provided without comment.  Quite interesting.

novel protease resistant peptide shuttles able to cross the blood-brain barrier (BBB) by binding to a specific brain receptor


A Catalan Research Institute based in Barcelona (Spain) has identified novel protease resistant peptide shuttles able to cross the blood-brain barrier (BBB) by binding to a specific brain receptor. These shuttles are a powerful alternative to carry a wide variety of small and large molecules as cargos. This represents a novel opportunity to develop new delivery carriers able to cross actively a range of biological barriers.

New and innovative aspects

These compounds are novel drug delivery carriers that provide a non-invasive, non-antigenic, stable and receptor-specific way to transport drugs across the Blood-Brain Barrier and into the Central Nervous System.

These compounds show high permeability, biocompatibility, good solubility in water and resistance to proteases.


The treatment of most neurological disorders has not been fully addressed mainly because of the neuroprotective role of the blood-brain barrier (BBB) that hinders the delivery of many diagnostic and therapeutic agents into the brain. Consequently, therapeutic molecules and genes that might otherwise be effective in diagnosis and therapy do not cross the BBB in adequate amounts: 98% of compounds smaller than 400Da and 100% of larger ones do not reach further drug development stages.

Most central nervous system (CNS) diseases, however, are complex disorders with difficult molecular targets that require larger, safer and more selective drugs. As a result, brain tumors, neurodegenerative diseases such as Parkinson’s and Alzheimer’s, and central nervous system (CNS) diseases such as schizophrenia are not successfully treated. Therefore, finding an efficient CNS delivery system is one of the major challenges in neurological treatment and one our technology can potentially overcome.

One of the best approaches for drug delivery to the brain is the use of endogenous transport mechanisms, such as receptor-mediated transcystosis. Peptides are biocompatible molecules able to transport cargos (i.e. therapeutic compounds) to specific tissues such as the brain. However, one of the main limitations of peptides as therapeutic agents is their low stability in plasma.

The use of non-natural amino acids in peptidic sequences can circumvent this problem because they are resistant to human serum proteases. Using this approach, we obtained several modified peptides. Two of them were selected based on their protease resistance and transport capacity across the blood-brain barrier, using a specific endogenous receptor. Both peptides showed enhanced membrane permeability in vitro in comparison to standard peptides and even greater stability in plasma (over 24h).

Main advantages of its use

Novel delivery technology that provides a non-invasive, non-antigenic, permeable, stable, soluble and receptor-specific way to transport drugs across the BBB and into the CNS.

This technology may ultimately allow the delivery of therapeutic agents, even large ones, across the BBB and other biological barriers, thus increasing the effectiveness of existing or new drugs.

Potential of application in a wide number of fields and in transport through various biological barriers.


Biotechnological and Pharmaceutical companies specialized in drug discovery, drug delivery, neurological disorders, tools to cross the Blood-brain barrier. The final aim is to increase the efficiency of existing molecules for the treatment of neurological disorders.

Molecule and treatment design, drug manufacture, treatment of neurological disorders, drug delivery across the blood-brain barrier (BBB).

Intellectual property status

This invention is protected by a priority application in Spain and we plan to apply for a PCT in due time.


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Reported by: Dr. Venkat S. Karra, Ph.D.

A new proof-of-concept study shows that plasma concentrations of precursor fragments of the neuropeptide enkephalin (proenkephalin A, or PENK-A) are elevated in patients with acute stroke compared with those with TIA and nonischemic events.

Researchers are making efforts to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease.

Although the mature neuropeptides are degraded within minutes, their precursor fragments are much more stable and represent neuropeptide synthesis in stoichiometric relations. “They are therefore well suited as biomarkers and may be suitable for measurement in clinical settings,” said Dr. Doehner.

The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders.

{Ernst  A., Kohrle  J., Bergmann  A.;  Proenkephalin A 119—159, a stable proenkephalin. A precursor fragment identified in human circulation, Peptides 27 2006 1835-1840
Ernst  A., Suhr  J., Kohrle  J., Bergmann  A.;  Detection of stable N-terminal protachykinin A immunoreactivity in human plasma and cerebrospinal fluid, Peptides 29 2008 1201-1206}

Researchers are making efforts to use these precursor fragments as markers to distinguish an ischemic stroke from a transient ischemic attack (TIA) or an intracerebral hemorrhage.

The authors strongly hope that it may help to advance the use of biomarkers in the clinical evaluation of stroke patients.

Despite the limitations, elevated PENK-A levels correlated with stroke severity and with brain lesion size, and they predicted mortality and more functional disability.

“There is clearly an unmet need to establish biomarker-guided prognostic and functional evaluations for patients with stroke, said the lead author Wolfram Doehner, MD, PhD, from the Center for Stroke Research, in Berlin, Germany

The new report was published in Journal of the American College of Cardiology.







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