Here's some encouraging research news

FROM: BioMedCentral ( a super web site for medical rresearch
information!)

Public release date: 6-Nov-2002

A pathway towards cures for Parkinson's and cancer

Researchers studying the Hedgehog signaling pathway have identified small
molecules that could form the foundations of exciting new treatments for
Parkinson's disease and certain cancers.

New research published in Journal of Biology - the open access journal
for exceptional research - has identified small molecules that are able
to stimulate or block the Hedgehog signalling pathway, which is essential
to the development, maintenance and repair of cells in the human body.
The potential of these molecules to be used as drugs to treat both
degenerative diseases and cancer is exciting as their small size may
allow these molecules to enter all parts of the body and cross the blood
brain barrier, eliminating the need for injections of therapeutics
directly into the target site.

The Hedgehog signaling pathway is crucial to the development of healthy
animals as well as the maintenance and repair of adult cells. Hedgehog
genes were first identified in the fruitfly, and were so called because
fly embryos with a defect in this gene were covered in bristles. The
central role of the Hedgehog signalling pathway in the regulation of the
growth and division of specific types of cells makes it of great interest
to researchers investigating diseases like Parkinson's that are
characterised by a lack of particular cells as the central nervous system
degenerates. Finding drugs that can stimulate the Hedgehog signaling
pathway and lead to the production of new cells could potentially cure
this disease. It is also hoped that by developing drugs that block the
Hedgehog signalling pathway researchers will be able to induce the
regression of tumours in patients with certain cancers that depend on
this pathway (specifically, basal cell carcinoma and medulloblastoma).

Recent research has shown the Hedgehog protein can itself reduce the
behavioural impairments and neuronal loss that occur in animal models of
the Parkinson's disease suggesting that manipulating this pathway may
well deliver new treatment. One major drawback of using the Hedgehog
protein to manipulate the signaling pathway is that, because of it large
size, it has to be administered by direct injection into the brain.

In the Journal of Biology article, a team of researchers led by Jeffrey A
Porter of the biotechnology company, Curis Inc, of Cambridge
Massachusetts, and including colleagues from Columbia University in New
York, report their screen of around 140,000 synthetic molecules for the
ability to stimulate or inhibit the Hedgehog signalling pathway. One of
the molecules was studied further by creating around 300 chemical
derivatives. Using this method the researchers were able to identify a
range of active molecules that could have exciting therapeutic benefits.

Porter and colleagues then went on to characterise the small synthetic
molecules to find out how they worked in living organisms, hopeful that
this would give them further understanding of the Hedgehog signalling
pathway. They found their small molecules were interacting with a poorly
understood protein that is found on the surface of developing cells. This
protein, called Smoothened, helps cells respond to the Hedgehog protein.

The interaction of the Smoothened protein with the synthetic small
molecules suggests that the Hedgehog signalling pathway may involve
similar small molecules to those synthesised in this study.

The authors conclude, "As a drug a Hedgehog agonist [one of the new
molecules they have identified] would represent an attractive alternative
to an expensive Hedgehog protein therapeutic."


###
This article will be published online and made available free of charge
on Wednesday November 6, in line with the publisher's policy of providing
immediate open access to original research: http://jbiol.com/1/2/10

The second issue of Journal of Biology will also include minireview and
research news articles that will also be made freely available from
http://jbiol.com, and which will be added to the press site ahead of
publication.

Journal of Biology (http://jbiol.com) is a new international journal,
published by BioMed Central, which provides immediate open access to
research articles of exceptional interest. It will only publish research
articles of the highest standard, similar to those published by Nature,
Science or Cell. While these journals restrict access to only those who
pay for a subscription, all research articles published in Journal of
Biology will be permanently available free of charge and without
restrictions, ensuring the widest possible dissemination of the work.

Contact details:

Journal of Biology
Editor Dr Theodora Bloom
E-mail [log in to unmask]
Telephone 44-207-323-0323
Facsimile 44-207-631-9961

Author Dr Jeffery A Porter, Curis, Inc.,
E-mail: [log in to unmask]
Telephone 617-503-6568
Facsimile 617-503-6501

http://jbiol.com/press/

Journal of Biology
Editor in Chief: Martin Raff
Website: http://jbiol.com
Publisher: BioMed Central
Format: online and print
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