Gene cream offers hope for psoriasis sufferers

By Tanya Hollis
Wednesday, 27 March, 2002

A Melbourne research group has become one of the first in the world to create a gene cream that successfully penetrates psoriasis lesions.

The work - a collaboration between Antisense Therapeutics (ASX: ANP) and the Murdoch Childrens Research Institute - is to be published in the May edition of the Journal of Investigative Dermatology (White et al).

The antisense compound targets a protein called insulin-like growth factor-I receptor (IGF-1R), which works to regulate skin cell division in psoriasis, a chronic skin condition affecting thousands of Australians.

Dubbed DT1064, the molecule is intended as a first-line topical treatment in a market estimated to be worth $1 billion annually.

In its latest experiment, the researchers showed the gene cream formulation could penetrate human psoriasis lesions that had been biopsied and maintained for a couple of days in a laboratory culture dish.

The group leader with MCRI's Dermal Therapeutics laboratory, Dr Christopher Wraight, said psoriasis patients were desperate for new treatments, with existing drugs proving inadequate in reversing the disease.

"We have shown that we can make DT1064 penetrate a psoriasis lesion," Wraight said.

"This shows the important concept that this molecule, which we have proven to work in the animal system, can be made in such a way that human patients will be able to use it also."

Reversed

In mid 2000, the researchers published a paper in Nature Biotechnology showing that the antisense inhibitor reversed the process of psoriasis when it was injected into mouse models with lesions created from human tissue.

"This showed that we could effectively reverse the terrible overgrowth of skin one sees in psoriasis," he said.

"When we tested our drug on special mice we found it cured their psoriasis lesions."

Following that success, Wraight said the researchers concentrated on putting the DT1064 molecule into a formulation patients could use, with the favoured delivery system being a topical cream.

"At the same time, probably the most important activity we commenced was looking to find a partner to take us with that formulation to develop it further and to put it into patients," he said.

Enter Antisense Therapeutics, which in 2001 formed a founding research partnership with MCRI whereby the company gained exclusive marketing rights to therapies developed from DT1064 (renamed ATL1101 after the collaboration).

In return, the MCRI received a stake of about five per cent in ATL, as well as valuable access to the company's US shareholder and antisense world leader, Isis Pharmaceuticals.

ATL's CEO, Mark Diamond, said that under the research agreement the company would develop ATL1101 into a formulation suitable for human patients using Isis' enabling technology.

He said Wraight's group would providing scientific support for pre-clinical and clinical development, with the next step for the ATL1101 research being the commencement of pre-clinical safety trials.

MCRI has also agreed to use its expertise in the area to generate laboratory data on expected efficacy of the treatment in other skin disorders.

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