Combination Therapy May Treat Rare Neurological Childhood Disorders

New therapeutic technique for a rare genetic disorder that leads to childhood dementia and premature death, can bring a revolution in the approach to treating it.

New therapeutic technique for Fatal Sanfilippo syndrome – a rare genetic disorder that leads to childhood dementia and premature death in children as young as 2 years old, can bring a revolution in the approach to treating it, as per a study at Canadian Glycomics Network.

Sanfilippo syndrome is a type of lysosomal storage disorders occuring in pediatric patients that is characterized by the absence or defectiveness of the enzymes, needed for the breakdown of certain sugars. These sugars then begin to build up in the brain, causing severe damage.

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University of South Florida researchers have found that the blood-brain barrier is severely damaged in inherited diseases of metabolism like Sanfilippo Syndrome type B (MPS III B).

‘New therapeutic technique using a combination of gene therapy and transplantation of hematopoietic (blood-forming) stem cells for Fatal Sanfilippo syndrome – a rare genetic disorder that leads to childhood dementia and premature death in children as young as 2 years old, can bring a revolution in the approach to treating it. The technique would serve as a new tool for clinicians to also treat a range of rare genetic conditions that affect the brain.’

Symptoms include childhood dementia, behavioral problems, and sleep disturbance, inability to speak, and death before the age of 20. The syndrome shares common pathology with other types of diseases in the same family of lysosomal storage disorders. As such only a few types have a treatment, with no cure at present.

"We are using a combination of gene therapy, stem cells, and small molecules to restore metabolic defects in the patient's brain cells. First results in the mouse models of the disease are very encouraging", says Dr. Alexey Pshezhetsky, Professor at CHU Ste-Justine and lead GlycoNet Investigator on this project.

The disease can affect about 1 in 5,000 births with some of the diseases being more frequent in specific populations such as Tay-Sachs disease affecting Ashkenazi Jewish and French Canadians or Sandhoff disease with high prevalence in northern Saskatchewan.

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Treatment Approach in Sanfilippo Syndrome

Enzyme replacement therapy is used to treat certain lysosomal storage disorders that do not affect the brain, on a weekly or monthly basis injection. The same does not work well with Sanfilippo syndrome, as the injected enzymes cannot reach the brain.

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This is due to the presence of a physical barrier between the brain and the bloodstream – blood-brain barrier, that allows only selected molecules to pass through the brain and ultimately the enzymes do not pass in.

The study team thus used a combination of gene therapy and transplantation of hematopoietic (blood-forming) stem cells – a one-time treatment to potentially cure or ameliorate the disease (similar to bone marrow replacement therapy). The patient's stem cells are first harvested and genetically corrected to eliminate enzyme defects followed by injecting them back to the patient.

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The test, developed by scientists at the Institute for Global Food Security at Queen's, can detect enzyme markers of disease known as proteases in humans, animals and food products.

These healthy blood cells can now secrete functional enzymes and proliferate and migrate to different tissues including the brain. Promising preliminary results were witnessed by the study team in their mouse models.

"About two-thirds of lysosomal storage disorders affect the brain. If we find out how to treat Sanfilippo syndrome, we can extend our knowledge to other similar diseases. I think it's important for people to know that recent discoveries lead to a paradigm shift for pediatric healthcare. Even if diseases are rare or ultra-rare we are not leaving patients behind but are developing customized ways to treat them," says Pshezhetsky.

The study states that the new approach would serve as a new tool for clinicians to treat a range of rare genetic conditions that affect the brain. The team further plans to gather more data before the use of therapy in human patients.

Source-Medindia