Stem cell study tackles devastating genetic paraplegia

Brisbane’s National Centre for Adult Stem Cell Research will commence a pilot study into a devastating genetic disease in which active young people progressively develop paraplegia.

The little-known disease, Hereditary Spastic Paraplegia is estimated to affect about 1000 Australians, but the mutations responsible may lurk in the genes of an unknown higher percentage of the population.

The first signs are catching the toes, stumbling and tripping. Walking becomes increasingly difficult. Many eventually require a walking aid with a significant number needing a wheelchair.

The study will use adult stem cells from people with Hereditary Spastic Paraplegia as the first step on the path to developing treatments to restore nerve function damaged by the disease.

The $100,000 funding for the study was raised by people with the disease through the HSP Research Foundation. The participants will donate their cells to create a ‘bank’ of adult stem cells for the study.

The project is led by Centre Director Professor Alan Mackay-Sim and Centre Group Leader, neurologist Associate Professor Carolyn Sue of Sydney’s Kolling Institute of Medical Research.

"We believe this will be the world’s first collection of stem cells from people with this disease," Professor Mackay-Sim said.

"The pilot project will take nasal biopsies from at least 10 people with HSP, all of whom have mutations in the SP4 gene. This mutation is present in about 40 per cent of the HSP population."

The research team will grow and differentiate these into nerve cells then assess the function of the SP4 gene compared to cells from a control group of healthy volunteers.

"We will then use the screening facilities at Griffith University’s Eskitis Institute to test candidate drugs to correct the cellular functions caused by the mutation. We hope to generate pilot data from this initial study to take to other funding agencies."

President of HSP Research Foundation Robin Bligh said the rarity of the disease meant little research had been conducted worldwide.

"Some of the genes responsible have been identified to enable genetic testing but there is no cure as yet on the horizon," he said.

"The Foundation has been unsuccessful in securing government and philanthropic grants because the disease is so rare.

"But the prevalence could be much higher than current estimates as it is often misdiagnosed as anything from MS to severe arthritis."

He said while most cases result from a single parent with a dominant defective gene, it is also possible for two people who unknowingly carry a recessive defective gene to pass the disease to their children, although they themselves exhibit no symptoms.

Its existence is commonly not revealed until the person is aged between 20 and 40 and begins to experience muscle weakness causing difficulty walking.

The age of onset means a person with the disease faces the prospect of spending the bulk of their lives progressively more seriously incapacitated by the disease.

"We turned to Griffith University to conduct the study after learning of its success with other neurological diseases such as Parkinson’s, and particularly for its work targeting neglected diseases, of which HSP is definitely one!" Mr Bligh said.

The funding will employ a dedicated stem-cell scientist supported by a team experienced in neurological conditions.

(Source: Griffith University: October 2008)