Personalised treatment on horizon for rare genetic disease patients

UK researchers have identified the most serious genetic mutations responsible for a rare condition that causes blindness, opening the door for personalised treatment and tailored gene therapies.

Bardet-Biedl
syndrome (BBS) is an inherited
disease that causes blindness, learning difficulties, extra fingers and toes and obesity and can lead to serious kidney problems. It affects around 500 people in the UK, and symptoms
often appear during childhood, but it is difficult to predict the severity of
the disease.

Researchers tested patients with BBS to see which of 16 known genes were responsible for
their condition. They then looked at their medical history and conducted
surveys to match up the patients' symptoms with the type of genetic mutation
they had. The research will allow doctors to predict the type and severity of symptoms a patient is likely to have, based on
their genome.

'Parents ask us "What is the future going to look
like for my child?" and we are now making some headway in being able to
answer those questions', said Dr
Elizabeth Forsythe from the Beales
Laboratory at University College
London, who led the research and was presenting the results at the annual
conference of the British Society for
Genetic Medicine. 'By identifying patterns in the types of genetic
mutations people have, we can give them a better idea of the challenges they're
going to face so they can prepare for them'.

People with a severe mutation type commonly found in the BBS10 gene on average developed
blindness earlier in life and were
more likely to have severe kidney
problems, the study reported. However, people with a common mutation in the BBS1 gene appeared to have milder
symptoms, and developed blindness up to a decade later.

The work will help specialists in the BBS clinics to
prioritise the patients who are the most likely to develop serious problems.
This means that patients who are less likely to develop severe complications,
or whose symptoms will appear later in life, may not have to attend clinic
appointments as frequently.

There is currently no
way to treat the underlying cause of BBS, but this research opens up the
potential to treat specific mutations
with tailored therapies.

'Understanding these mutations provides a springboard for targeted therapy', said
Dr Forsythe. 'There are several new
types of treatment that have the potential to target the different types of
gene mutations we have studied'.

For example, patients with severe mutations could be
treated with exon-skipping therapy or read-through therapy, both
experimental genetically targeted treatments that have yielded positive results
in preliminary trials.

'Exon-skipping works like a plaster on the mutated section of the gene, while read-through
therapy can convert a type of severe
mutation into a milder one', explained Dr Forsythe. 'We think that 1 in 10 of our patients could be helped
with read-through therapy, and 1 in 12 with exon-skipping therapy'.