Testing a new treatment strategy that could help children with two rare neurodegenerative diseases

Niemann-Pick type C1 (NPC1) disease and Wolfram syndrome (WS) are both rare, life-limiting neurodegenerative diseases that mainly affect children. Currently, there is no cure for either – and current treatment options are extremely limited. Dr Sovan Sarkar of the University of Birmingham is carrying out laboratory tests to find out whether existing therapies used for other health conditions could help slow the progression of symptoms that affect the nervous system in NPC1 and WS. His ultimate goal is to develop an effective new treatment strategy that could help improve the quality of life and extend life expectancy for children born with these devastating conditions.

This project is jointly funded by Action Medical Research and LifeArc.

How are children’s lives affected now?

Although Niemann-Pick type C1 (NPC1) and Wolfram syndrome (WS) are distinct illnesses, they both involve the gradual loss of nerve cells. This process – called neurodegeneration – causes a range of symptoms affecting the brain and central nervous system, which get worse over time. 

“Alongside symptoms specific to NPC1 or WS, children will experience a variety of challenges linked to neurodegeneration – such as problems affecting walking, swallowing, hearing or thinking,” says Dr Sarkar. “Sadly, many children’s lives will be cut short due to severe complications related to this progressive nerve damage.”

Both NPC1 and WS are linked to problems with autophagy – the body’s natural process for clearing cellular waste. When this malfunctions, unwanted materials build up, eventually leading to nerve cell death.

“There’s an urgent need for new treatments that can help slow down or halt neurodegeneration in NPC1 and WS – improving the outlook for children born with these conditions and their families,” says Dr Sarkar. 

How could this research help?

“Our ultimate goal is to repurpose existing drugs to develop an effective new treatment strategy for children with NPC1 and WS that can slow or halt nerve cell death,” says Dr Sarkar.

The researchers previously found that autophagy helps support nerve cell survival by maintaining the levels of a metabolite called NAD, which is vital for energy metabolism. They will now investigate whether existing drugs that enhance autophagy and nutritional supplements that boost NAD levels could offer a promising treatment approach for NPC1 and WS.

“We will carry out experiments to assess the effects of these two types of treatment on nerve cells and ‘mini-brains*’ generated from patient skin cells and grown in laboratory dishes,” says Dr Sarkar.

If their results are encouraging, the team plans to advance this new treatment strategy to clinical trials involving patients with NPC1 and WS as soon as possible. Since these medicines are already in use and their safety and dosage are established, this should help accelerate this process.

“Since problems with autophagy are implicated in other neurodegenerative conditions, these repurposed medicines could potentially help many more children in the future,” says Dr Sarkar. 

*3D mini-brain-like structures made up of nerve cells and grown in laboratory dishes.

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